Inter-domain distance prediction based on deep learning for domain assembly.

AlphaFold2 achieved a breakthrough in protein structure prediction through the end-to-end deep learning method, which can predict nearly all single-domain proteins at experimental resolution. However, the prediction accuracy of full-chain proteins is generally lower than that of single-domain proteins because of the incorrect interactions between domains. In this work, we develop an inter-domain distance prediction method, named DeepIDDP. In DeepIDDP, we design a neural network with attention mechanisms, where two new inter-domain features are used to enhance the ability to capture the interactions between domains. Furthermore, we propose a data enhancement strategy termed DPMSA, which is employed to deal with the absence of co-evolutionary information on targets. We integrate DeepIDDP into our previously developed domain assembly method SADA, termed SADA-DeepIDDP. Tested on a given multi-domain benchmark dataset, the accuracy of SADA-DeepIDDP inter-domain distance prediction is 11.3% and 21.6% higher than trRosettaX and trRosetta, respectively. The accuracy of the domain assembly model is 2.5% higher than that of SADA. Meanwhile, we reassemble 68 human multi-domain protein models with TM-score ≤ 0.80 from the AlphaFold protein structure database, where the average TM-score is improved by 11.8% after the reassembly by our method. The online server is at http://zhanglab-bioinf.com/DeepIDDP/.

Exacerbation of atherosclerosis by STX17 knockdown: Unravelling the role of autophagy and inflammation.

Syntaxin 17 (STX17) has been identified as a crucial factor in mediating the fusion of autophagosomes and lysosomes. However, its specific involvement in the context of atherosclerosis (AS) remains unclear. This study sought to elucidate the role and mechanistic contributions of STX17 in the initiation and progression of AS. Utilizing both in vivo and in vitro AS model systems, we employed ApoE knockout (KO) mice subjected to a high-fat diet and human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL) to assess STX17 expression. To investigate underlying mechanisms, we employed shRNA-STX17 lentivirus to knock down STX17 expression, followed by evaluating autophagy and inflammation in HUVECs. In both in vivo and in vitro AS models, STX17 expression was significantly upregulated. Knockdown of STX17 exacerbated HUVEC damage, both with and without ox-LDL treatment. Additionally, we observed that STX17 knockdown impaired autophagosome degradation, impeded autophagy flux and also resulted in the accumulation of dysfunctional lysosomes in HUVECs. Moreover, STX17 knockdown intensified the inflammatory response following ox-LDL treatment in HUVECs. Further mechanistic exploration revealed an association between STX17 and STING; reducing STX17 expression increased STING levels. Further knockdown of STING enhanced autophagy flux. In summary, our findings suggest that STX17 knockdown worsens AS by impeding autophagy flux and amplifying the inflammatory response. Additionally, the interaction between STX17 and STING may play a crucial role in STX17-mediated autophagy.

Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1.

BACKGROUND: While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure. METHODS: FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1. RESULTS: Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival. CONCLUSIONS: Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients.

Pathfinder: Protein folding pathway prediction based on conformational sampling.

The study of protein folding mechanism is a challenge in molecular biology, which is of great significance for revealing the movement rules of biological macromolecules, understanding the pathogenic mechanism of folding diseases, and designing protein engineering materials. Based on the hypothesis that the conformational sampling trajectory contain the information of folding pathway, we propose a protein folding pathway prediction algorithm named Pathfinder. Firstly, Pathfinder performs large-scale sampling of the conformational space and clusters the decoys obtained in the sampling. The heterogeneous conformations obtained by clustering are named seed states. Then, a resampling algorithm that is not constrained by the local energy basin is designed to obtain the transition probabilities of seed states. Finally, protein folding pathways are inferred from the maximum transition probabilities of seed states. The proposed Pathfinder is tested on our developed test set (34 proteins). For 11 widely studied proteins, we correctly predicted their folding pathways and specifically analyzed 5 of them. For 13 proteins, we predicted their folding pathways to be further verified by biological experiments. For 6 proteins, we analyzed the reasons for the low prediction accuracy. For the other 4 proteins without biological experiment results, potential folding pathways were predicted to provide new insights into protein folding mechanism. The results reveal that structural analogs may have different folding pathways to express different biological functions, homologous proteins may contain common folding pathways, and α-helices may be more prone to early protein folding than ß-strands.

A Method for the Synthesis of Thioindoles through Copper-Catalyzed C-S Bond Coupling Reaction.

We herein report the copper-catalyzed C-S bond coupling reaction of indoles with N-thiosuccinimides, resulting in moderate to excellent yields of mono- and bis-sulfenylated compounds such as arylthioindoles, alkylthioindoles, selenylated indoles, and cysteine-substituted indoles. Thioarylation and thioglycosylation at the C2 position of indole alkaloids in the Radix Isatidis were achieved via structural modification. The first total syntheses of isatindigotindolosides III and IV have been successfully carried out. The electrophilic sulfenyl bromides generated in situ can play an important role in the catalytic cycle.

Accuracy of intraoral versus desktop scanners used in digitizing polyvinyl siloxane impression for fabricating a CAD-CAM customized post and core.

PURPOSE: This in vitro study aimed to compare the 3-dimensional (3D) accuracy of intraoral and desktop scanners when digitizing the post and core polyvinyl siloxane impressions. MATERIAL AND METHODS: Ten extracted human teeth were prepared to build a post space in the root canal. Each tooth was scanned using a micro-computed tomography device (MCT), and the slice data were reconstructed as controls. A conventional quadrant polyvinyl siloxane impression was made and scanned thrice using an intraoral scanner (IOS) and a desktop blue-light scanner (IMS), with one of the scans randomly selected as the definitive cast. Precision was assessed by comparing the deviations among repeated scans. Trueness was evaluated by analyzing the deviations between the MCT and each definitive cast (MCT-IOS and MCT-IMS). The clinically acceptable root mean square (RMS) value was set to 50 µm. RESULTS: The mean RMS values of the repeated scans of IOS and IMS were 18.3 ± 3.9 µm and 13.9 ± 6.2 µm (P < 0.05), and the difference between them was 4.4 ± 5.9 µm. The mean RMS values of MCT-IOS and MCT-IMS were 28.3 ±3.0 µm and 31.3 ± 4.2 µm (P < 0.05), with a difference of 3.0 ± 2.9 µm. The RMS values were significantly lower than 50 µm (P < 0.05). CONCLUSIONS: The IOS showed slightly better trueness than the IMS but slightly lower precision. The precision and trueness of the two scanners for digitizing post and core impressions were acceptable for clinical application.

Hierarchical Solid-Additive Strategy for Achieving Layer-by-Layer Organic Solar Cells with Over 19 % Efficiency.

Layer-by-layer (LbL) deposition of active layers in organic solar cells (OSCs) offers immense potential for optimizing performance through precise tailoring of each layer. However, achieving high-performance LbL OSCs with distinct solid additives in each layer remains challenging. In this study, we explore a novel approach that strategically incorporates different solid additives into specific layers of LbL devices. To this end, we introduce FeCl3 into the lower donor (D18) layer as a p-type dopant to enhance hole concentration and mobility. Concurrently, we incorporate the wide-band gap conjugated polymer poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) into the upper acceptor (L8-BO) layer to improve the morphology and prolong exciton lifetime. Unlike previous studies, our approach combines these two strategies to achieve higher and more balanced electron and hole mobility without affecting device open-circuit voltage, while also suppressing charge recombination. Consequently, the power conversion efficiency (PCE) of the D18+FeCl3/L8-BO device increases to 18.12 %, while the D18/L8-BO+PFO device attains a PCE of 18.79 %. These values represent substantial improvements over the control device's PCE of 17.59 %. Notably, when both FeCl3 and PFO are incorporated, the D18+FeCl3/L8-BO+PFO device achieves a remarkable PCE of 19.17 %. In summary, our research results demonstrate the effectiveness of the layered solid additive strategy in improving OSC performance.

Periostin-targeted SDSSD peptide decorated calcium phosphate nanocomposites incorporation with simvastatin for osteoporosis treatment.

The limited options of anabolic drugs restrict their application potential in osteoporosis treatment, despite their theoretical superiority in therapeutic efficacy over antiresorptive drugs. As a prevailing strategy, nano-delivery systems could offer a wider choice of anabolic drugs. In this study, calcium phosphate nanocomposites incorporated with simvastatin (Sim) with periostin-targeting ability were designed and prepared for osteoporosis treatment. Carboxymethyl dextran (CMD) as an anionic and hydrophilic dextran derivative was used to stabilize CaP. In addition, periosteum-targeted peptide (SDSSD) was further grafted on CMD to achieve the bone targeting function. In a one-step coordination assembly strategy, hydrophobic anabolic agent Sim and SDSSD-CMD graft (SDSSD-CMD) were incorporated into the CaP nanoparticles forming SDSSD@CaP/Sim nanocomposites. The resulting SDSSD@CaP/Sim possesses uniform size, great short-term stability and excellent biocompatibility. Moreover, SDSSD@CaP/Sim exhibited a reduced release rate of Sim and showed slow-release behaviour. As anticipated, the nanocomposites exhibited bone bonding capacity in both cellular and animal studies. Besides, SDSSD@CaP/Sim achieved obviously enhanced osteoporosis treatment effect compared to direct injection of Simin vivo. Therefore, our findings highlight the potential of SDSSD-incorporated and CaP-based nanocomposites as a viable strategy to enhance the therapeutic efficacy of anabolic drugs for osteoporosis treatment.

CD16 CAR-T cells enhance antitumor activity of CpG ODN-loaded nanoparticle-adjuvanted tumor antigen-derived vaccinevia ADCC approach.

BACKGROUND: Combinatorial immunotherapy strategies for enhancing the responsiveness of immune system have shown great promise for cancer therapy. Engineered nanoformulation incorporated toll-like receptor (TLR) 9 agonist CpG ODN has shown more positive results in suppressing tumor growth and can significantly enhance other immunotherapy activity with combinatorial effects due to the innate and adaptive immunostimulatory effects of CpG. RESULTS: In the present work, protamine sulfate (PS) and carboxymethyl ß-glucan (CMG) were used as nanomaterials to form nanoparticles through a self-assembly approach for CpG ODN encapsulation to generate CpG ODN-loaded nano-adjuvant (CNPs), which was subsequently mixed with the mixture of mouse melanoma-derived antigens of tumor cell lysates (TCL) and neoantigens to develop vaccine for anti-tumor immunotherapy. The obtained results showed that CNPs was able to effectively deliver CpG ODN into murine bone marrow-derived dendritic cells (DC) in vitro, and remarkably stimulate the maturation of DC cells with proinflammatory cytokine secretion. In addition, in vivo analysis showed that CNPs enhanced anti-tumor activity of PD1 antibody and CNPs-adjuvanted vaccine based on the mixture antigens of melanoma TCL and melanoma-specific neoantigen could not only induce anti-melanoma cellular immune responses, but also elicit melanoma specific humoral immune responses, which significantly inhibited xenograft tumor growth. Furthermore, CD16 CAR-T cells were generated by expressing CD16-CAR in CD3+CD8+ murine T cells. CONCLUSION: Our results eventually showed that anti-melanoma antibodies induced by CNPs-adjuvanted TCL vaccines were able to collaborate with CD16-CAR-T cells to generate an enhanced targeted anti-tumor effects through ADCC (antibody dependent cell cytotoxicity) approach. CD16 CAR-T cells has thus a great potential to be an universal promising strategy targeting on solid tumor synergistic immunotherapy via co-operation with TCL-based vaccine.

Hypervalent Iodine(III)-Mediated Umpolung Dialkoxylation of N-Substituted Indoles.

Herein, we report dialkoxylation of N-substituted indoles through a hypervalent iodine-mediated umpolung strategy, affording trans-2,3-dimethoxyindolines with up to 95% yield. In addition, C5-selective bromination of 2,3-dialkoxyindoline via NBS-mediated rearomatization was achieved. DFT calculation of the sequence of electrophilic addition and nucleophilic substitution pathway of N-substituted indoles has also been investigated.

Boosting nutrient starvation-dominated cancer therapy through curcumin-augmented mitochondrial Ca2+ overload and obatoclax-mediated autophagy inhibition as supported by a novel nano-modulator GO-Alg@CaP/CO.

BACKGROUND: By hindering energy supply pathway for cancer cells, an alternative therapeutic strategy modality is put forward: tumor starvation therapy. And yet only in this blockade of glucose supply which is far from enough to result in sheer apoptosis of cancer cells. RESULTS: In an effort to boost nutrient starvation-dominated cancer therapy, here a novel mitochondrial Ca2+ modulator Alg@CaP were tailor-made for the immobilization of Glucose oxidase for depriving the intra-tumoral glucose, followed by the loading of Curcumin to augment mitochondrial Ca2+ overload to maximize the therapeutic efficiency of cancer starvation therapy via mitochondrial dysfunctions. Also, autophagy inhibitors Obatoclax were synchronously incorporated in this nano-modulator to highlight autophagy inhibition. CONCLUSION: Here, a promising complementary modality for the trebling additive efficacy of starvation therapy was described for cutting off the existing energy sources in starvation therapy through Curcumin-augmented mitochondrial Ca2+ overload and Obatoclax-mediated autophagy inhibition.

Determination of water in organic solvents and raw food products by fluorescence quenching of a crystalline vinyl-functionalized COF.

Covalent organic frameworks (COFs) with good chemical stability, flexible chemical functionalization, tunable pore sizes, and high specific surface areas have been increasingly employed in the field of fluorescence sensing. In this work, a crystalline vinyl-functionalized COF TzDa-V was facilely prepared through a room-temperature synthetic method via condensation reaction between 4,4',4″-(1,3,5-triazine-2,4,6-triyl)trianiline (Tz) and 2,5-diallyloxyterephthalaldehyde (Da-V). The intermolecular charge transfer (ICT) effect endowed the TzDa-V with fluorescence characteristic, and it was sensitive to trace water and can be quenched due to the disruption of ICT process by water. On this base, the prepared COF TzDa-V with excellent chemical/thermal stability was applied to sensing of trace water in common organic solvents such as DMF, acetone, THF, and ethyl acetate with rapid response (less than 10 s), satisfactory sensing range (0.5-18% water in DMF, 0.5-15% water in acetone, 0.5-16% water in THF, 0.5-5% in ethyl acetate, v/v), and high sensitivity. The limits of detection for water in DMF, acetone, THF, and ethyl acetate were 0.0497%, 0.0590%, 0.0502%, and 0.0766% (v/v), respectively. The proposed probe was successfully used for the detection of trace water in food products such as salt and sugar. The COF TzDa-V would be a good candidate for application in water sensing.

The Application of 3D Dense Face Alignment in Esthetic Rehabilitation.

This article describes a technique for making an esthetic treatment plan by using a virtual face scan reconstructed from digital photographs through three-dimensional dense face alignment (3DDFA) and intraoral scans. Portrait photographs were captured with a digital camera and were reconstructed to a virtual 3D face scan by 3DDFA. After scaling the virtual face scan to the correct size, intraoral scans and virtual face scans were aligned to create a 3D view of the patient. A virtual diagnostic waxing was created accordingly. In select cases, this technique can provide 3D esthetic predictions when 3D face imaging devices are not available.

miR-302a-3p targets FMR1 to regulate pyroptosis of renal tubular epithelial cells induced by hypoxia-reoxygenation injury.

NEW FINDINGS: What is the central question of this study? How does miR-302a-3p play a role in hypoxia-reoxygenation-induced pyroptosis of renal tubular epithelial cells? What is the main finding and its importance? Hypoxia-reoxygenation treatment upregulated the expression of miR-302a-3p in HK-2 cells, and then inhibited the transcription of FMRP translational regulator 1 (FMR1), so as to promote the activation of the NLRP3 inflammasome and aggravate the pyroptosis of HK-2 cells. miR-302a-3p was used as a molecular target in this study, which provides a new theoretical basis for the treatment of renal failure. ABSTRACT: Hypoxia-reoxygenation (H/R) induction can affect miRNA expression and then control NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis. This study investigated the mechanism of miR-302a-3p in H/R-induced renal tubular epithelial cell (RTEC) pyroptosis. Human HK-2 RTECs were induced by H/R. Lactate dehydrogenase content, cell activity and pyroptosis, and levels of NLRP3, GSDMD-N, caspase-1, interleukin (IL)-1ß, IL-18, superoxide dismutase, and malondialdehyde were detected to verify the effect of H/R on HK-2 cells. The NLRP3 inflammasome action was evaluated after H/R-induced HK-2 cells were treated with BAY11-7082, an inflammasome inhibitor. After inhibiting miR-302a-3p expression, the changes of pyroptosis were observed. The binding relation between miR-302a-3p and FMRP translational regulator 1 (FMR1) was verified. A function-rescue experiment verified the role of FMR1 in the regulation of pyroptosis. H/R-induced HK-2 cells showed significant pyroptosis injury, and the NLRP3 inflammasome was activated. After inhibiting the NLRP3 inflammasome, H/R-induced apoptosis was inhibited. After H/R treatment, miR-302a-3p in HK-2 cells was increased, and miR-302a-3p downregulation limited H/R-induced NLRP3 inflammasome-mediated pyroptosis. FMR1 is the target of miR-302a-3p. Inhibition of FMR1 alleviated the inhibition of H/R-induced HK-2 cell pyroptosis by miR-302a-3p inhibitor. Collectively, inhibiting miR-302a-3p can weaken its targeted inhibition on FMR1, thereby inhibiting the activation of NLRP3 inflammasomes and reducing caspase-1-dependent pyroptosis in HK-2 cells.

Self-assembling combretastatin A4 incorporated protamine/nanodiamond hybrids for combined anti-angiogenesis and mild photothermal therapy in liver cancer.

Tumor angiogenesis has been identified as an important factor in the development and progression of tumors, and anti-angiogenesis therapy has been recognized as an effective tumor therapy pattern. The unique characteristics of nanodiamonds (NDs) have been explored for photothermal therapy (PTT) against cancer, while the efficiency of mild PTT mediated by bare NDs was limited. The combination of different therapies into a single nanoplatform has shown great potential for synergistic cancer treatment. In this investigation, we integrated hydrophobic antiangiogenesis agent combretastatin A4 (CA4) into the protamine sulfate (PS) functionalized NDs hybrids (NDs@PS) with a noncovalent self-assembling method (CA4-NDs@PS) for potential combined anti-angiogenesis and mild PTT in liver cancer. The resulted CA4-NDs@PS NDs exhibited high drug loading ability, good dispersibility and colloidal stability. The near-infrared (NIR) laser irradiation could trigger the release of CA4 from CA4-NDs@PS NDs and elevate the temperature of CA4-NDs@PS NDs aqueous solution.In vitroresults illustrated that CA4-NDs@PS coupled with laser irradiation could remarkably enhance HepG-2 cells killing efficiency, leading to an enhanced photocytotoxicity. Furthermore,in vivoexperiments revealed that CA4-NDs@PS exhibited a highly synergistic anticancer efficacy with NIR laser irradiation in HepG-2 tumor-bearing mice. Altogether, our present study fabricated a novel NDs@PS-based nanoplatform for combined anti-tumor angiogenesis and mild PTT against liver cancer.

Self-assembled fluorescent hybrid nanoparticles-mediated collaborative lncRNA CCAT1 silencing and curcumin delivery for synchronous colorectal cancer theranostics.

BACKGROUND: Cancer synergistic therapy strategy in combination with therapeutic gene and small molecule drug offers the possibility to amplify anticancer efficiency. Colon cancer-associated transcript-1 (CCAT1) is a well identified oncogenic long noncoding RNA (lncRNA) exerting tumorigenic effects in a variety of cancers including colorectal cancer (CRC). RESULTS: In the present work, curcumin (Cur) and small interfering RNA targeting lncRNA CCAT1(siCCAT1) were co-incorporated into polymeric hybrid nanoparticles (CSNP), which was constructed by self-assembling method with two amphiphilic copolymers, polyethyleneimine-poly (D, L-lactide) (PEI-PDLLA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) (DSPE-mPEG). Owing to the multicolor fluorescence characteristics of PEI-PDLLA, the constructed CSNP could be served as a theranostic nanomedicine for synchronous therapy and imaging both in vitro and in vivo. Resultantly, proliferation and migration of HT-29 cells were efficiently inhibited, and the highest apoptosis ratio was induced by CSNP with coordination patterns. Effective knockdown of lncRNA CCAT1 and concurrent regulation of relevant downstream genes could be observed. Furthermore, CSNP triggered conspicuous anti-tumor efficacy in the HT-29 subcutaneous xenografts model with good biosafety and biocompatibility during the treatment. CONCLUSION: On the whole, our studies demonstrated that the collaborative lncRNA CCAT1 silencing and Cur delivery based on CSNP might emerge as a preferable and promising strategy for synergetic anti-CRC therapy.

Aplysin Retards Pancreatic Necrosis and Inflammatory Responses in NOD Mice by Stabilizing Intestinal Barriers and Regulating Gut Microbial Composition.

Aplysin is a brominated sesquiterpene with an isoprene skeleton and has biological activities. The purpose of this study is to investigate the inhibitory effect of aplysin on spontaneous pancreatic necrosis in nonobese diabetic (NOD) mice and its potential mechanisms. Results showed that NOD mice at 12 weeks of age showed obvious spontaneous pancreatic necrosis, damaged tight junctions of intestinal epithelia, and widened gaps in tight and adherens junctions. Aplysin intervention was able to alleviate spontaneous pancreatic necrosis in NOD mice, accompanied with decreased serum endotoxin levels and downregulated expressions of Toll-like receptor 4 and its related molecules MyD88, TRAF-6, NF-κB p65, TRIF, TRAM, and IRF-3, as well as protein levels of interleukin-1ß and interferon-ß in pancreatic tissues. In addition, we observed obvious improvements of intestinal mucosal barrier function and changes of gut microbiota in the relative abundance at the phylum level and the genus level in aplysin-treated mice compared with control mice. Together, these data suggested that aplysin could retard spontaneous pancreatic necrosis and inflammatory responses in NOD mice through the stabilization of intestinal barriers and regulation of gut microbial composition.

Esthetic appearances of anatomic contour zirconia crowns made by additive wet deposition and subtractive dry milling: A self-controlled clinical trial.

STATEMENT OF PROBLEM: Anatomic contour zirconia crowns are widely used in clinical dental practice because of their mechanical reliability and improved appearance. However, few studies have performed clinical evaluations of the esthetics of these crowns in terms of color and translucency gradient. PURPOSE: The purpose of this clinical trial was to compare the esthetic effect and color-matching behaviors of anatomic contour zirconia crowns manufactured with 3-dimensional (3D) gel deposition and dry milling methods. MATERIAL AND METHODS: Twenty-seven premolar teeth of 27 participants received 2 identical anatomic contour zirconia crowns fabricated by additive 3D gel deposition or dry milling. Color differences (ΔE) between the crown and natural control teeth were measured by a dental shade-matching device. Subjective color matching was rated by professionals using an extended visual rating scale for appearance match (EVRSAM) and by participants using a visual analog scale (VAS). Data were analyzed by using repeated measures ANOVA, the Bonferroni test, paired Student t test, Pearson chi-square test, and Wilcoxon test (α=.05). RESULTS: Significant differences were found in ΔE between zirconia crown and core types (P<.05); however, there was no significant interaction between these factors (P>.05). The average ΔE of crowns made by wet deposition and dry milling were 2.45 ±1.60 and 4.55 ±1.54 (P<.05). The mean crown ΔE was significantly higher if a gold cast post-and-core was placed rather than a prefabricated fiber post and composite core (P<.05). Consistent with these findings, subjective color matching was significantly higher in the wet deposition group than in the dry milling group as rated by EVRSAM and VAS (P<.05). CONCLUSIONS: Anatomic contour zirconia crowns fabricated by additive wet deposition were better matched to adjacent teeth and had excellent esthetics in terms of color and translucency gradient.

From one to all: self-assembled theranostic nanoparticles for tumor-targeted imaging and programmed photoactive therapy.

BACKGROUND: In recent years, multifunctional theranostic nanoparticles have been fabricated by integrating imaging and therapeutic moieties into one single nano-formulations. However, Complexity of production and safety issues limits their further application. RESULTS: Herein, we demonstrated self-assembled nanoparticles with single structure as a "from one to all" theranostic platform for tumor-targeted dual-modal imaging and programmed photoactive therapy (PPAT). The nanoparticles were successfully developed through self-assembling of hyaluronic acid (HA)-cystamine-cholesterol (HSC) conjugate, in which IR780 was simultaneously incorporated (HSCI NPs). Due to the proper hydrodynamic size and intrinsic targeting ability of HA, the HSCI NPs could accumulate at the tumor site effectively after systemic administration. In the presence of incorporated IR780, in vivo biodistribution and accumulation behaviors of HSCI NPs could be monitored by photoacoustic imaging. After cellular uptake, the HSCI NPs would disintegrate resulting from cystamine reacting with over-expressed GSH. The released IR780 would induce fluorescence "turn-on" conversion, which could be used to image tumor sites effectively. Upon treatment with 808 nm laser irradiation, PPAT could be achieved in which generated reactive oxygen species (ROS) would produce photodynamic therapy (PDT), and subsequently the raised temperature would be beneficial to tumor photothermal therapy (PTT). CONCLUSION: The self-assembled HSCI NPs could act as "from one to all" theranostic platform for high treatment efficiency via PPAT pattern, which could also real-time monitor NPs accumulation by targeted and dual-modal imaging in a non-invasive way.

[THAP11 mediates the proliferation and apoptosis of esophageal cancer cells via inhibiting ubiquitination of p53].

OBJECTIVE: To investigate the effects of thanatos-associated protein 11 (THAP11) on the proliferation and apoptosis of esophageal cancer cell and the underlying mechanism.
 Methods: Expression of THAP11 in human esophageal epithelial cells (Het-1A) and esophageal cancer cells (Eca109, TE-1, Ec 9706) were detected by Western blotting. Esophageal cancer TE-1 cells were divided into 3 groups: a normal control (NC) group, a negative control (LV-NC) group and a THAP11 (LV-THAP11) group. Then the cell proliferation were detected by MTT assay, cell apoptosis were detected by flow cytometry, caspase-3 and caspase-9 levels were detected by caspases kits. Ubiquitination of p53 was determined in esophageal cancer TE-1 cells.
 Results: Expression of THAP11 was reduced in esophageal cancer cells compared with human esophageal epithelial cells (P<0.05). After transfection with LV-THAP11 in TE-1 cells, cell viability was reduced (P<0.05), while apoptosis rate and caspase-3 and caspase-9 levels were increased (P<0.05), indicating that THAP11 inhibited growth of esophageal cancer cells. In addition, the THAP11 increased the levels of p53 (P<0.05) and inhibited the ubiquitination of p53 regulated by MDM2. 
 Conclusion: THAP11 may inhibit the proliferation of esophageal cancer cells by inhibiting ubiquitination of p53.