Discovery of Ten Anti-HIV Hit Compounds and Preliminary Pharmacological Mechanisms Studies.

BACKGROUND: The research and development of HIV drugs is very important, but at the same time it is a long cycle and expensive system project. High-throughput drug screening systems and molecular libraries of potential hit compounds remain the main ways for the discovery of hit compounds with anti-HIV activity. OBJECTIVE: The aim of this study was to screen out the hit compounds against HIV-1 in the natural product molecule library and the antiviral molecule library, and elucidate the molecular mechanism of their inhibition of HIV-1, so as to provide a new choice for AIDS drug research. METHODS: In this study, a drug screening system using HIV Rev-dependent indicator cell line (Rev-A3R5-GFP reporter cells) with pseudoviruses (pNL4-3) was used. The natural drug molecule library and antiviral molecule library were screened, and preliminary drug mechanism studies were performed. RESULTS: Ten promising hit compounds were screened. These ten molecules and their drug inhibitory IC50 were as follows: Cephaeline (0.50 µM), Yadanziolide A (8.82 µM), Bruceine D (2.48 µM), Astragaloside IV (4.30 µM), RX-3117 (1.32 µM), Harringtonine (0.63 µM), Tubercidin (0.41 µM), Theaflavine-3, 3'-digallate (0.41 µM), Ginkgetin (10.76 µM), ZK756326 (5.97 µM). The results of the Time of additions showed that except for Astragaloside IV and Theaflavine-3, 3'-digallate had a weak entry inhibition effect, and it was speculated that all ten compounds had an intracellular inhibition effect. Cephaeline, Harringtonine, Astragaloside IV, Bruceine D, and Tubercidin may have pre-reverse transcriptional inhibition. Yadanziolide A, Theaflavine-3, 3'-digallate, Ginkgetin and RX-3117 may be in the post-reverse transcriptional inhibition. The inhibitory effect of ZK 75632 may be in the reverse transcriptional process. CONCLUSION: A drug screening system using Rev-A3R5-GFP reporter cells with pseudoviruses (pNL4-3) is highly efficient. This study provided potential hit compounds for new HIV drug research.

Prediction of effluent total nitrogen and energy consumption in wastewater treatment plants: Bayesian optimization machine learning methods.

The control of effluent total nitrogen (TN) and total energy consumption (TEC) is a key issue in managing wastewater treatment plants. In this study, effluent TN and TEC predictive models were established by selecting influent water quality and process control indicators as input features. The prediction performance of machine learning methods under different random seeds was explored, the moving average method was used for data amplification, and the Bayesian algorithm was used for hyperparameter optimization. The results showed that compared with the traditional hyperparameter optimization method for effluent TN prediction, the coefficient of determination (R2) increased by 0.092 and 0.067, reaching 0.725, and the root mean square error (RMSE) decreased by 0.262 and 0.215 mg/L, reaching 1.673 mg/L, respectively, after Bayesian optimization and data amplification. During TEC prediction, R2 increased by 0.068 and 0.042, reaching 0.884, and the RMSE decreased by 232.444 and 197.065 kWh, reaching 1305.829 kWh, respectively.

A polymeric nanocarrier that eradicates breast cancer stem cells and delivers chemotherapeutic drugs.

BACKGROUND: Drug nanocarriers can markedly reduce the toxicities and side effects of encapsulated chemotherapeutic drugs in the clinic. However, these drug nanocarriers have little effect on eradicating breast cancer stem cells (BCSCs). Although compounds that can inhibit BCSCs have been reported, these compounds are difficult to use as carriers for the widespread delivery of conventional chemotherapeutic drugs. METHODS: Herein, we synthesize a polymeric nanocarrier, hyaluronic acid-block-poly (curcumin-dithiodipropionic acid) (HA-b-PCDA), and explore the use of HA-b-PCDA to simultaneously deliver chemotherapeutic drugs and eradicate BCSCs. RESULTS: Based on molecular docking and molecular dynamics studies, HA-b-PCDA delivers 35 clinical chemotherapeutic drugs. To further verify the drug deliver ability of HA-b-PCDA, doxorubicin, paclitaxel, docetaxel, gemcitabine and camptothecin are employed as model drugs to prepare nanoparticles. These drug-loaded HA-b-PCDA nanoparticles significantly inhibit the proliferation and stemness of BCSC-enriched 4T1 mammospheres. Moreover, doxorubicin-loaded HA-b-PCDA nanoparticles efficiently inhibit tumor growth and eradicate approximately 95% of BCSCs fraction in vivo. Finally, HA-b-PCDA eradicates BCSCs by activating Hippo and inhibiting the JAK2/STAT3 pathway. CONCLUSION: HA-b-PCDA is a polymeric nanocarrier that eradicates BCSCs and potentially delivers numerous clinical chemotherapeutic drugs.

Dynamics of Microbial Community Structure, Function and Assembly Mechanism with Increasing Stand Age of Slash Pine (Pinus elliottii) Plantations in Houtian Sandy Area, South China.

Establishing slash pine plantations is the primary method for restoring sandification land in the Houtian area of South China. However, the microbial variation pattern with increasing stand age remains unclear. In this study, we investigated microbial community structure and function in bare sandy land and four stand age gradients, exploring ecological processes that determine their assembly. We did not observe a significant increase in the absolute abundance of bacteria or fungi with stand age. Bacterial communities were dominated by Chloroflexi, Actinobacteria, Proteobacteria, and Acidobacteria; the relative abundance of Chloroflexi significantly declined while Proteobacteria and Acidobacteria significantly increased with stand age. Fungal communities showed succession at the genus level, with Pisolithus most abundant in soils of younger stands (1- and 6-year-old). Turnover of fungal communities was primarily driven by stochastic processes; both deterministic and stochastic processes influenced the assembly of bacterial communities, with the relative importance of stochastic processes gradually increasing with stand age. Bacterial and fungal communities showed the strongest correlation with the diameter at breast height, followed by soil available phosphorus and water content. Notably, there was a significant increase in the relative abundance of functional groups involved in nitrogen fixation and uptake as stand age increased. Overall, this study highlights the important effects of slash pine stand age on microbial communities in sandy lands and suggests attention to the nitrogen and phosphorus requirements of slash pine plantations in the later stages of sandy management.

Clinical Evaluation of Continuous Renal Replacement Therapy Combined with Peritoneal Lavage for Severe Acute Pancreatitis: A Retrospective Cohort Study.

BACKGROUND We aimed to investigate the clinical efficacy of continuous renal replacement therapy (CRRT) in combination with peritoneal lavage for the treatment of severe acute pancreatitis. MATERIAL AND METHODS We retrospectively reviewed data from 52 patients with severe acute pancreatitis between January 2014 and December 2021 at Jiangyin People's Hospital. The patients were divided into 2 groups: CRRT (n=26) and CRRT in combination with peritoneal lavage (n=26). The following results and outcomes were retrospectively compared: procalcitonin, interleukin-6, and C-reactive protein levels, duration of systemic inflammatory response, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, length of hospital stay, inpatient hospital costs, incidence of complications, and mortality. RESULTS There were significant differences in interleukin-6 and procalcitonin levels and APACHE-II scores after 3 and 7 days of treatment. The duration of systemic inflammatory response, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, and length of hospital stay were considerably shorter in the combination group than in the CRRT group (P<0.01). Inpatient hospital costs were significantly lower in the combination group than in the CRRT group (P<0.01). However, incidence of complications and mortality showed no significant differences between the 2 groups. CONCLUSIONS CRRT combined with peritoneal lavage is an important adjuvant therapy in the early stages of acute severe acute pancreatitis and has better clinical efficacy than CRRT alone.

Preparation and characterization of mussel-inspired hydrogels based on methacrylated catechol-chitosan and dopamine methacrylamide.

A novel mussel-inspired adhesive hydrogel with enhanced adhesion based on methacrylated catechol-chitosan (MCCS) and dopamine methacrylate (DMA) was prepared via photopolymerization. The structure and morphology of the MCCS/DMA adhesive hydrogel were investigated by using FTIR, NMR, XRD, TG, and SEM. The rheological and texture properties, swelling and degradation characteristics, as well as the adhesion mechanism of the hydrogels were also examined. These results revealed that the MCCS/DMA hydrogels have a dense double cross-linking network structure with porous internal microstructures, and exhibited controllable swelling and degradation properties, good thermostability, and stable rheological characteristics. Furthermore, the adhesive mechanism of MCCS/DMA hydrogel has been confirmed by the FTIR and 2D correlation FTIR spectroscopy. Additionally, the results of in vitro cytotoxicity assessment indicated that the resulting hydrogels have good cytocompatibility. Overall, the MCCS/DMA adhesive hydrogel may have potential applications in medical bioadhesives.

Preparation and In Vitro Bioactivity Study of a Novel Hollow Mesoporous Bioactive Glass Nanofiber Scaffold.

In this study, a novel three-dimensional hollow mesoporous bioactive glass nanofiber scaffold has been synthesized with a template-assisted sol-gel method using bacterial cellulose (BC) as a template and nonionic triblock copolymer (P123) as a pore-directing agent, ethyl orthosilicate (TEOS), calcium nitrate tetrahydrate (CN), and triethyl phosphate (TEP) as glass precursors. Scanning and transmission electron microscopies, X-ray diffraction, nitrogen adsorption-desorption, and nuclear magnetic resonance method were applied to characterize the morphology, crystal structure, and chemical structure of the mesoporous bioactive glass nanofiber scaffold. Furthermore, the in vitro bioactivity and biocompatibility were also explored. The obtained scaffold depicted nanofiber-like morphology and interconnected three-dimensional network structure that replicated the BC template. The scaffold showed a large specific surface area (230.0 cm2 g-1) and pore volume (0.2 m3 g-1). More importantly, the scaffold exhibited excellent apatite-forming ability and cellular biocompatibility. We believe that the hollow mesoporous bioactive glass nanofiber scaffold has great potential application in bone tissue regeneration.

Curcumin and its nano-formulations: Defining triple-negative breast cancer targets through network pharmacology, molecular docking, and experimental verification.

Background: Curcumin (CUR) displays the capability of suppressing the proliferation and metastasis of various cancer cells. However, the effects and underline mechanisms of CUR to treat triple-negative breast cancer (TNBC) have not been systematically elucidated with an appropriate method. Methods: In the present research, a combination method of network pharmacology, molecular docking, and in vitro bio-experiment was used to investigate the pharmacological actions and underline mechanisms of CUR against TNBC. First, common targets of CUR and TNBC were screened via Venny 2.1.0 after potential CUR-related targets and targets of TNBC were got from several public databases. Then, the Gene Ontology (GO) function and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed on the Metascape website, and the network of compound-targets-pathways was constructed via Cytoscape software. Moreover, the network of protein-protein interaction was constructed by the STRING database to screen potential targets. Moreover, molecular docking was applied to affirm the interaction of CUR with the screened top 10 potential targets. Finally, in vitro experiments were used to further verify the effects and mechanisms of CUR and its nano-formulation (CUR-NPs) against TNBC. Results: Forty potential targets of CUR against TNBC were obtained. STAT3, AKT1, TNF, PTGS2, MMP9, EGFR, PPARG, NFE2L2, EP300, and GSK3B were identified as the top 10 targets of CUR against TNBC. In vitro experiment verified that CUR and CUR-NPs could not only restrain the invasion, migration, and proliferation of MDA-MB-231 cells but also induce their apoptosis. In addition, molecular docking demonstrated that CUR could bind spontaneously with the screened top 10 targeted proteins, and a real-time PCR experiment demonstrated that both CUR and CUR-NPs could downregulate the genetic expression levels of the 10 targets. Moreover, according to the CUR-targets-pathways network, PI3K-Akt, EGFR tyrosine kinase inhibitor resistance, JAK-STAT, Foxo, and HIF-1 signaling pathways were identified as the important pathways of CUR effects on TNBC. Among them, the inhibiting effects of CUR and CUR-NPs on the JAK-STAT signaling pathway were further verified by the western blot analysis. Conclusion: Taken together, the present research demonstrates that CUR and CUR-NPs have pharmacological effects against TNBC via a multi-target and multi-pathway manner.

Laparoscopic VS. Open splenectomy and oesophagogastric devascularisation for liver cirrhosis and portal hypertension: A retrospective cohort study.

BACKGROUND: We compared laparoscopic splenectomy combined with oesophagogastric devascularisation vs. open splenectomy combined with oesophagogastric devascularisation in patients with portal hypertension secondary to liver cirrhosis. MATERIALS AND METHODS: This study included 192 patients diagnosed with portal hypertension and severe gastroesophageal varices at our hospital between January 2002 and December 2018; 62 patients underwent laparoscopic splenectomy combined with oesophagogastric devascularisation (laparoscopic group), and 130 patients underwent the open procedure (open group). The results and outcomes were compared retrospectively. RESULTS: The median blood loss was significantly less in the laparoscopic group than in the open group (180 vs. 380 mL, P < 0.001). The length of hospitalisation was shorter (6 vs. 11 days, P < 0.001) and the complication rate was lower in the laparoscopic group (P < 0.001). The general complication rates were 23.8% and 4.8% (P < 0.001), and the surgical complication rates were 56.1% and 24.2% (P < 0.001) in the open and laparoscopic groups, respectively. During a postoperative follow-up period of 10-60 months, the incidence of oesophagogastric variceal rebleeding showed no significant difference between groups. CONCLUSION: Laparoscopic splenectomy combined with oesophagogastric devascularisation is technically feasible and safe in selected patients. Compared with the open group, the laparoscopic group showed a less volume of blood loss, shorter length of hospitalisation, and fewer postoperative complications but similar long-term outcomes.

[Construction of Tn5 transposon insertion mutants of Ralstonia solanacearum isolated from Pogostemon cablin].

Ralstonia solanacearum strain PRS-84 used in this study was isolated from diseased Pogostemon cablin plants in our previous study.The competent cells of R.solanacearum strain PRS-84 were transformed by electroporation with Tn5 transposon and then were plated on TTC agar plates containing kanamycin to select for kanamycin-resistant colonies.The detection of kanamycin-resistant gene in kanamycin-resistant colonies was performed by PCR.Further,the flanking fragments of Tn5 transposon insertion site in the mutants were amplified by inverse PCR,and the flanking fragments were sequenced and analyzed.The results indicated that the kanamycin-resistant colonies were obtained in the transformation experiment of R.solanacearum strain PRS-84 by electroporation with Tn5 transposon.A specific band of approximately 700 bp was amplified by PCR from kanamycin-resistant colonies.The flanking sequences of Tn5 transposon insertion site in the transformants were obtained by inverse PCR.After sequencing and sequence analysis of Tn5 transposon insertion site in mutants,we preliminarily speculated that the Tn5 transposon inserted in the typ A gene,rec O gene and gid A gene in three mutants,respectively.A random mutagenesis system of R.solanacearum strain PRS-84 by electroporation with Tn5 transposon has been established,and the Tn5 insertion mutants have been obtained.This study might facilitate the creation of mutant library and the discovery of the virulence gene of R.solanacearum isolated from P.cablin.

A practical random mutagenesis system for Ralstonia solanacearum strains causing bacterial wilt of Pogostemon cablin using Tn5 transposon.

A practical random mutagenesis system of Ralstonia solanacearum by electroporation with Tn5 transposon was established, which may be utilized to provide genetic approach to study virulence genes of R. solanacearum strains and create nonpathogenic mutants for biological control of bacterial wilt in Pogostemon cablin. R. solanacearum strain PRS-84 used in this study was isolated from P. cablin plants infected with bacterial wilt. The bacterial suspension of R. solanacearum strain PRS-84 was mixed with Tn5 transposome complex and the mixture was transformed by electroporation. The electroporated cells were then spread on the 2, 3, 5-triphenyltetrazolium chloride agar plates containing kanamycin to select the kanamycin-resistant colonies. Several factors which determined the bacterial transformation efficiency were optimized. The transformation process was shown to be optimal at the electric field strength of 12.5 kV cm-1. Bacterial cells harvested at mid-exponential phase gave the highest transformation efficiency. 10 µg mL-1 kanamycin was found to be the optimal concentration for transformant selection. Tn5 insertion mutants of R. solanacearum strain PRS-84 were identified by PCR amplification and Southern blot analysis. Mutants subcultured for 100 passages were also detected by PCR amplification and Southern blot analysis. Furthermore, pathogenicity screening test of mutants was performed by inoculating in vitro regenerated patchouli plants. Results revealed that mutants with a single Tn5 insertion in their genomes were obtained from R. solanacearum strain PRS-84, and the Tn5 insertion could be stably inherited in the mutants. Then, mutants with reduced pathogenicity were selected.

TXNDC9 promotes hepatocellular carcinoma progression by positive regulation of MYC-mediated transcriptional network.

The thioredoxin domain containing proteins are a group of proteins involved in redox regulation and have been recently reported to be associated with tumor progression. However, the role of thioredoxin proteins in hepatocellular carcinoma (HCC) remains largely unknown. Here in our study, we demonstrated that thioredoxin domain containing protein 9 (TXNDC9) was over-expressed in HCC and promoted HCC progression. We found that TXNDC9 expression was amplified in HCC tissues and associated with an advanced grade of HCC. And, we demonstrated that overexpression of TXNDC9 was correlated with poor prognosis of HCC. Furthermore, by using CRISPR-Cas9 mediated TXNDC9 knockout and RNA-seq analysis, we found that TXNDC9 accelerated HCC proliferation regulation. Moreover, we demonstrated that TXNDC9 directly interacted with MYC and knockout/knockdown of TXNDC9 decreased the protein levels of MYC and inhibited MYC-mediated transcriptional activation of its targets. Besides, we identified that TXNDC9 was trans-activated by FOXA1, JUND, and FOSL2 in HCC. Taken together, our study unveiled an oncogenic role of TXNDC9 in HCC and provided a mechanistic insight into the TXNDC9 mediated gene regulation network during HCC development.

Laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma in 157 patients: A case controlled study with propensity score matching at two Chinese centres.

BACKGROUND: The aim of this study was to investigate the long-term outcomes and perioperative outcomes of laparoscopic hepatectomy (LH) versus open hepatectomy (OH) for hepatocellular carcinoma (HCC) between well-matched patient groups. METHODS: We retrospectively reviewed data from 1535 hepatocellular carcinoma patients who underwent liver resection between January 2002 and December 2016 at two Chinese centres. Propensity score matching of patients in a ratio of 1:1 was conducted and 157 patients were matched. RESULTS: The median blood loss (150 vs 380 ml, P < 0.001) was significantly less with LH. The laparoscopic group had shorter hospital stay (6 vs 10 days, P < 0.001) and less complication rate (6.4% vs 24.2%,P < 0.001). There were no significant differences in overall survival and disease-free survival between LH and OH. There were no significant differences in perioperative and long-term outcomes. CONCLUSION: Laparoscopic hepatectomy is technically feasible and safe in selected patients. LH showed similar long-term outcomes, associated with less blood loss, shorter hospital stay, and fewer postoperative complications in selected patients with HCC compared with OH.

Treatment choice by patients with obstructive sleep apnea: data from two centers in China.

BACKGROUND: Standard management has been recommended for obstructive sleep apnea (OSA) by several guidelines, but patient choice in the practical setting is unclear. METHODS: A survey nested in two prospective cohort studies of OSA (enrollment: 2001-2010) in China. The last interview was conducted between July 2014 and May 2015, using a comprehensive 10-point questionnaire administered in a face-to-face or telephone interview, and assessed (I) whether the participant had received any OSA treatment; (II) why he or she had decided for or against treatment; (III) what treatment was received; (IV) whether the participant used continuous positive airway pressure (CPAP) or OA daily; and (V) the perceived efficacy of therapy. RESULTS: A total of 4,097 subjects with a mean age of 45 years [37-55] responded to this survey, with a response rate of 79.4% (4,097/5,160); 2,779 subjects (67.8%) did not receive any treatment: 1,485 (53.4%) believed that their condition was not serious, despite severe OSA in 53.7% of the patients. A multivariate regression showed that the decision to receive treatment was associated with: age between 45-59 years [odds ratio (OR) 0.805, 95% CI: 0.691-0.936; P<0.001], female gender (OR 0.492, 95% CI: 0.383-0.631; P<0.001), severe OSA (OR 1.92, 95% CI: 1.01-3.64; P<0.001), hypertension (OR 1.414, 95% CI: 1.209-1.654; P<0.001) and diabetes (OR 1.760, 95% CI: 1.043-2.972; P=0.034). In subjects receiving treatment (n=1,318), 50.9% reported negative perceptions about the treatments. CONCLUSIONS: Nearly two thirds of Chinese patients choose not to receive treatment after OSA diagnosis, and nearly half are negative about their treatments for OSA. This requires clinical attention, and warrants further study in different geographic settings.

Induction of defense-related enzymes in patchouli inoculated with virulent Ralstonia solanacearum

Background: Defense-related anti-oxidative response is a vital defense mechanism of plants against pathogen invasion. Ralstonia solanacearum is an important phytopathogen. Bacterial wilt caused by R. solanacearum is the most destructive disease and causes severe losses in patchouli, an important aromatic and medicinal plant in Southeast Asia. The present study evaluated the defense response of patchouli inoculated with virulent R. solanacearum. Results: Results showed that the basic enzymatic activities differed not only between the leaves and stems but also between the upper and lower parts of the same organ of patchouli. POD, SOD, PPO, and PAL enzymatic activities were significantly elevated in leaves and stems from patchouli inoculated with R. solanacearum compared to those in control. The variation magnitude and rate of POD, PPO, and PAL activities were more obvious than those of SOD in patchouli inoculated with R. solanacearum. PAGE isoenzymatic analysis showed that there were one new POD band and two new SOD bands elicited, and at least two isoformic POD bands and two SOD bands were observably intensified compared to the corresponding control. Conclusion: Our results suggest that not only defense-related enzymatic activities were elevated but also the new isoenzymatic isoforms were induced in patchouli inoculated with R. solanacearum.

[Application of a self-made steel wire guide in the treatment of avulsion fractures of tibial posterior cruciate ligament].

OBJECTIVE: To explore the effect of a self-made guiding needle of steel wire in guiding the wire through the tibial tunnel for the treatment of avulsion fractures of tibial posterior cruciate ligament with open reduction and wire fixation. METHODS: From February 2011 to June 2014, a total of 22 patients with avulsion fractures of tibial posterior cruciate ligament underwent surgical treatments were analyzed, including 14 males and 8 females with an average age of 35.6 years old (ranged, 17 to 63 years old). According to Meyers classification, 9 patients were classified as type II, 13 patients were classified as type III. All the patients underwent open reduction and wire fixation with medial knee "L" shape approach. A wire guiding needle was used to guide the wire through the tibial tunnel during operation. RESULTS: With the assistance of wire guidance needles, wires passed through the tibial tunnel rapidly during the operation in all the 22 patients. All the patients were followed up, X-ray imagings 6 months after operation showed the fractures healed well. The average follow-up time in all patients was 6 months (ranged, 6 to 12 months). The averaged Lysholm knee score in 22 knee was 92.7 +/- 3.4. All patients' posterior drawer test were negative. CONCLUSION: Self-made wire guiding needle can simplify the operation procedures in which the wires pass through the tibial tunnel, shorten the operation time, reduce the surgical trauma and complications, and be worthy of clinical application.

[PRELIMINARY APPLICATION OF VIRTUAL PREOPERATIVE RECONSTRUCTION PLANNING IN Pilon FRACTURES].

OBJECTIVE: To investigate the application value of three-dimensional reconstruction and virtual preoperative planning for Pilon fractures. METHODS: Between July 2010 and June 2014, 16 patients with closed Pilon fracture were treated, including 12 males and 4 females with an average age of 36.5 years (range, 22-53 years) and a mean disease duration of 10.2 days (range, 6-14 days). According to AO/Orthopaedic Trauma Association (AO/OTA) typing, 2 cases were rated as 43.B2 type, 3 cases as 43.B3 type, 3 cases as 43.C1 type, 2 cases as 43.C2 type, and 6 cases as 43.C3 type. The preoperative CT data from 16 patients were imported into Mimics10.01 software to establish the detailed fracture three-dimensional digital models. Virtual operation of fracture reduction and implanting internal fixation was performed on the models, and the optional surgical planning was made. Based on the virtual preoperative planning, operations were performed. RESULTS: Established detailed three-dimensional Pilon fracture digital models could perfectly reflect the fracture characteristics, could be observed at any direction, and aided for fracture classification accurately. Virtual fracture operations of reduction, internal fixation and other could be performed to simulate the clinical operation, which could assist the surgeon better preoperative planning in achieving visual presentation and improving the communication. The operation time was 70-130 minutes (mean, 87.8 minutes); intraoperative blood loss volume was 30-150 mL (mean, 71.9 mL). The wounds healed by first intension in all patients. The mean follow-up time was 11.6 months (range, 8-18 months). Postoperative radiological results at 3 groups showed good anatomic reduction according to the Burwell-Charnley criteria, and the fracture healing time was 3-6 months (mean, 3.7 months). There was no complication of internal fixation loosening or breakage during follow-up. The American Orthopedic Foot and Ankle Society (AOFAS) score was 71-100 (mean, 92.3); the results were excellent in 10 cases, good in 5 cases, and fair in 1 case, with an excellent and good rate of 93.8% at last follow-up. No loss of fracture reduction was observed on the X-ray film. CONCLUSION: The clinical feasibility of virtual reconstruction preoperative planning is good in the treatment of Pilon fractures, which helps surgeons better understanding Pilon fracure and making the surgical planning.

Impact of the nature and size of the polymeric backbone on the ability of heterobifunctional ligands to mediate shiga toxin and serum amyloid p component ternary complex formation.

Inhibition of AB(5)-type bacterial toxins can be achieved by heterobifunctional ligands (BAITs) that mediate assembly of supramolecular complexes involving the toxin's pentameric cell membrane-binding subunit and an endogenous protein, serum amyloid P component, of the innate immune system. Effective in vivo protection from Shiga toxin Type 1 (Stx1) is achieved by polymer-bound, heterobifunctional inhibitors-adaptors (PolyBAITs), which exhibit prolonged half-life in circulation and by mediating formation of face-to-face SAP-AB(5) complexes, block receptor recognition sites and redirect toxins to the spleen and liver for degradation. Direct correlation between solid-phase activity and protective dose of PolyBAITs both in the cytotoxicity assay and in vivo indicate that the mechanism of protection from intoxication is inhibition of toxin binding to the host cell membrane. The polymeric scaffold influences the activity not only by clustering active binding fragments but also by sterically interfering with the supramolecular complex assembly. Thus, inhibitors based on N-(2-hydroxypropyl) methacrylamide (HPMA) show significantly lower activity than polyacrylamide-based analogs. The detrimental steric effect can partially be alleviated by extending the length of the spacer, which separates pendant ligand from the backbone, as well as extending the spacer, which spans the distance between binding moieties within each heterobifunctional ligand. Herein we report that polymer size and payload of the active ligand had moderate effects on the inhibitor's activity.

Cationic glyconanoparticles: their complexation with DNA, cellular uptake, and transfection efficiencies.

There is a need to synthesize new gene delivery vehicles that can deal with the problems of endosomal escape and nuclear entry. We propose cationic glycopolymer-stabilized gold nanoparticles as an effective gene delivery system. The cationic glyconanoparticles synthesized were revealed to be biocompatible and are resistant to aggregation in physiological conditions. The complexation of DNA to the cationic glyconanoparticles is determined by agarose gel electrophoresis. The localization of the DNA-glyconanoparticles inside the Hela cell line and their mechanism of uptake is studied by confocal microscopy. Finally, the efficacy of the glyconanoparticles as gene delivery vehicles in vitro is studied by their complexation with cyanine fluorescence protein encoded plasmid, and the transfection efficiency is found to be comparable to the commercially available control Lipofectamine 2000.

Cationic glyco-functionalized single-walled carbon nanotubes as efficient gene delivery vehicles.

Carbon nanotubes are an emerging class of nanomaterials that are receiving enormous attention in the field of biomedicines due to their biocompatibility, degradability, cell penetrating abilities, and, more specifically, their remarkable ability to localize in the nucleus of the cell without the need of nuclear localizing signals. They are used as drug and gene delivery agent for in vitro studies; however, their transfection efficiencies in vitro are still questionable. We report here the surface functionalization of single-walled carbon nanotubes (SWNTs) with cationic glycopolymers and their use as an in vitro gene transfer agent. The copolymer modified SWNTs are found to be biocompatible and exhibit transfection efficiencies that are comparable to the commercially available agent lipofectamine 2000.