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Silicosis is an important industrial health problem for those workers exposed to silica. The present study aimed to investigate the sensitivity and specificity of combined detection of biomarkers in early auxiliary diagnosis of silicosis, the risk factors of silicosis were also studied. The study sample comprised 65 workers who had clinical silicosis and 70 matched control subjects who were exposed to silica but did not have clinical silicosis. The levels of superoxide dismutase, malondialdehyde, interleukin 6 (IL-6), tumor necrosis factor-alpha, and cholinesterases in the serum of 135 subjects were measured. After completing the biochemical assays, a logistic regression model based on the above biochemical determination results was established, and the receiver operating characteristic curve was used for judging the discrimination ability of different statistical indexes. The expression levels of MDA, IL-6, and TNF-alpha in serum samples of patients with stage I silicosis and MDA and IL-6 in serum samples of patients with stage II silicosis were all significantly higher. Results from logistic regression analysis showed that ChEs were protective factors for silicosis, while age, chronic respiratory symptoms, IL-6, and MDA were risk factors. The areas under the ROC curve (AUC) were 0.86 (IL-6), 0.81 (MDA), and 0.65 (TNF-alpha or ChEs). AUC-ROC = 0.90 (95%CI:0.84–0.95). The diagnostic efficiency of IL-6 combined with MDA and TNF-alpha was better than that of any single biomarker.

Accident duration prediction is the basis of freeway emergency management, and timely and accurate accident duration prediction can provide a reliable basis for road traffic diversion and rescue agencies. This study proposes a method for predicting the duration of freeway accidents based on social network information by collecting Weibo data of freeway accidents in Sichuan province and using the advantage that human language can convey multi-dimensional information. Firstly, text features are extracted through a TF-IDF model to represent the accident text data quantitatively; secondly, the variability between text data is exploited to construct an ordered text clustering model to obtain clustering intervals containing temporal attributes, thus converting the ordered regression problem into an ordered classification problem; finally, two nonparametric machine learning methods, namely support vector machine (SVM) and k-nearest neighbour method (KNN), to construct an accident duration prediction model. The results show that when the ordered text clustering model divides the text dataset into four classes, both the SVM model and the KNN model show better prediction results, and their average absolute error values are less than 22 %, which is much better than the prediction results of the regression prediction model under the same method.

Hexameric structure formation through packing of three C-terminal helices and an N-terminal trimeric coiled-coil core has been proposed as a general mechanism of class I enveloped virus entry. In this process, the C-terminal helical repeat (HR2) region of viral membrane fusion proteins becomes transiently exposed and accessible to N-terminal helical repeat (HR1) trimer-based fusion inhibitors. Herein, we describe a mimetic of the HIV-1 gp41 HR1 trimer, N3G, as a promising therapeutic against HIV-1 infection. Surprisingly, we found that in addition to protection against HIV-1 infection, N3G was also highly effective in inhibiting infection of human β-coronaviruses, including MERS-CoV, HCoV-OC43, and SARS-CoV-2, possibly by binding the HR2 region in the spike protein of β-coronaviruses to block their hexameric structure formation. These studies demonstrate the potential utility of anti-HIV-1 HR1 peptides in inhibiting human β-coronavirus infection. Moreover, this strategy could be extended to the design of broad-spectrum antivirals based on the supercoiling structure of peptides.

This study aims to guide the community life circle to create a green, travel-supportive built environment. It quantitatively analyzes the variations in car usage behavior based on the level of the built environment of the community and objectively reflects the car usage behavior based on the parking space utilization rate (PSUR). Ordinary least squares (OLS) and gradient boosting decision tree (GBDT) models were developed to describe the impact of the built environment on this utilization rate. An empirical analysis of the model was also conducted using the multisource, heterogeneous parking data of commercial parking facilities in the main urban area of Chongqing, China; the data include records of parking survey, points of interest, and road networks. The results showed that the GBDT model had a better fitting degree than the OLS model considering nonlinear effects. In terms of the contribution of community-built environment variables, distance to business center (14.30%), population density (14.20%), and land use mix (12.60%) considerably affect the PSUR, indicating that these variables have an important influence on the use of private cars. All built environment variables have nonlinear relationships, and the threshold effects reflect a complex relationship between the built environment and car usage behavior. This study provides refined suggestions for the spatial design and transformation of the community life circle.

Short peptide-based inhibition of fusion remains an attractive goal in antihuman immunodeficiency virus (HIV) research based on its potential for the development of technically and economically desirable antiviral agents. Herein, we report the use of the dithiol bisalkylation reaction to generate a series of m-xylene thioether-stapled 22-residue α-helical peptides that have been identified as fusion inhibitors targeting HIV-1 glycoprotein 41 (gp41). The peptide sequence is based on the helix-zone binding domain of the gp41 C-terminal heptad repeat region. We found that one of these stapled peptides, named hCS6ERE, showed promising inhibitory potency against HIV-1 Env-mediated cell-cell fusion and viral replication at a level comparable to the clinically used 36-mer peptide T20. Furthermore, combining hCS6ERE with a fusion inhibitor having a different target site, such as HP23, produced synergistic anti-HIV-1 activity. Collectively, our study offers new insight into the design of anti-HIV peptides with short sequences.

Pneumoconiosis is a serious occupational disease that often occurs to coal workers with no early diagnosis and effective treatment at present. Diffuse pulmonary fibrosis is the major pathological change of pneumoconiosis, and its mechanism is still unclear. Epigenetics is involved in the development of many diseases, and it is closely associated with fibrosis. In this study, we investigated whether DNA methylation contributes to the pathogenesis of pulmonary fibrosis in pneumoconiosis. By exposure to coal dust or silica dust, we established the models of coal worker's pneumoconiosis (CWP), which showed an increased expression of COL-I, COL-III. We further found that DNMT1, DNMT3a, DNMT3b, MBD2, MeCP2 protein expression changed. Pretreatment with DNMT inhibitor 5-aza-dC reduced expression of COL-I, COL-III, and reduced pulmonary fibrosis. In summary, our results showed that DNA methylation contributes to dust-induced pulmonary fibrosis and that it may serve as a theoretical basis for testing DNA methyltransferase inhibitors in the treatment of CWP.

Antimicrobial peptides (AMPs) are regarded as next-generation antibiotics to replace conventional antibiotics due to their rapid and broad-spectrum antimicrobial properties and far less sensitivity to the development of pathogen resistance. However, they are susceptible to proteolysis in vivo by endogenous or bacterial proteases as well as induce the lysis of red blood cells, which prevent their intravenous applications. In this work, polyion complex (PIC) micelles of the cationic AMP MSI-78 and the anionic copolymer methoxy poly(ethylene glycol)-b-poly(α-glutamic acid) (mPEG-b-PGlu) were prepared to develop novel antimicrobial agents for potential application in vivo. With an increase in molar ratio of mPEG-b-PGlu to MSI-78, the complexation ability of the PIC micelles increased. FITC-labeled MSI-78 showed a sustained release from the PIC micelles. More importantly, these PIC micelles greatly decreased the hemolytic toxicity of MSI-78 to human red blood cells, without influencing its antimicrobial activity. Thus, this approach could be used as a suitable in vivo delivery method of AMPs in the future.

Gene therapy as a strategy for disease treatment requires safe and efficient gene delivery systems that encapsulate nucleic acids and deliver them to effective sites in the cell. Due to the insecurity of viral vectors, non-viral vectors have gained great attention recently. Additional advantages of non-viral vectors include their safety, flexibility in packaging nucleic acids, and ease of production. To construct an ideal gene carrier, peptides can be incorporated into non-viral gene delivery systems as functional motifs to overcome the current barriers in gene delivery. In this review, we summarize recent developments in peptide-based gene delivery vector research.

To overcome barriers associated with gene delivery, a series of peptides consisting of multifunctional fragments, including a cationic amphiphilic α-helical antimicrobial peptide (AMP), a cell penetrating peptide (CPP), TAT, a stearyl moiety, and cysteine residues, were designed and synthesized for evaluation as non-viral gene vectors. TAT and AMP segments were utilized to mediate cellular uptake and endosomal escape, respectively. Stearyl moieties provide an intramolecular hydrophobic environment to promote AMPs to form an α-helical conformation in PBS, and this is beneficial for DNA binding, cellular uptake, and endosomal escape. The α-helical content of the peptides, as well as the particle size, zeta potential, and morphology of the peptide/DNA complexes, was characterized. Fluorescence activated cell sorting (FACS) and confocal microscopy data showed that the peptides were able to efficiently translocate a pGL3 control plasmid across the plasma membrane via endocytosis, and then they successfully evaded endosomal entrapment and possible metabolic degradation. Moreover, one of the peptide vectors exhibited a high transfection efficiency similar to that of Lipofectamine 2000, concomitant with lower cytotoxicity. Overall, a combination of the four functional segments tested was used to generate a non-viral gene vector that synergistically promoted cellular uptake, endosomal escape, and gene expression.

Peptide vectors offer a promising gene delivery approach because of their biocompatibility and ease of functionalization. This article describes the design and evaluation of a series of multifunctional peptides and their gene delivery abilities. The peptides were composed of a cell-penetrating segment, stearyl moiety, cationic amphiphilic α-helical segment, and cysteine and histidine residues. The proton sponge effect of histidine residues at low pH and the α-helical conformation should improve endosomal escape. Inclusion of D-type amino acids should improve proteolytic stability. The conformation, particle size and zeta potential of peptide/DNA complexes were characterized by circular dichroism and dynamic light scattering. Gene transfection efficiency was investigated by fluorescence-activated cell sorting and confocal microscopy. Transfection efficiencies of the designed peptide vectors were better than those of C18-C(LLKK)3C-TAT and Lipo2000. D-Type peptide C18-c(llhh)3c-tat showed three times higher transfection efficiency at N/P ratios of 6 and 8 than Lipo2000 in NIH-3T3 and 293T cells. All peptides showed lower cytotoxicity than Lipo2000 in NIH-3T3 and 293T cells. In the presence of trypsin or serum in vitro, D-type peptides showed better stability than L-type peptides. Overall, the designed histidine-enriched multifunctional peptide gene vectors promoted cellular uptake, endosomal escape and gene transfection.

Sustained drug release at specific sites is clinically favorable for the treatment of many diseases. The discovery of new polymeric materials suitable for prolonging drug release, improving therapeutic efficiency, and decreasing systemic toxicity is always of great interest in local sustained-release drug delivery systems (LSRDDSs). In this study, a new cross-linked cyanoacrylate (CA)-based LSRDDS is developed, in which the drug depot consists of a formulation of methoxyethyl cyanoacrylate (MOE-CA) with the cross-linking agent CA-PEG-CA. The MOE-CA endowed the CA polymer with good degradability. The drug-release profile could be affected by the structure and composition ratio of the MOE-CA/CA-PEG-CA monomer. The liquid CA monomer could dissolve the drug without using other solvents, and could polymerize into a solid glue just in a few seconds after injection. An optimal formulation loaded with 5-fluorouracil (J-Fu-1.25) showed excellent anticancer activity both in vitro and in vivo, with 50% survival of the mice and no significant systemic toxicity detected during the experiment. The CA depot might affect the blood flow in microvessels of tumors, thus contributing to the synergetic anticancer effect of 5-fluorouracil. We believe that this work provides a practical, biodegradable, and biocompatible LSRDDS for chemotherapeutic drug delivery that can also be applied universally with various drugs for certain therapeutic aims.

The approval of the erythropoietin (EPO) mimetic peptide drug peginesatide in 2012 was a breakthrough for the treatment of secondary anemia. However, due to severe allergic reactions, peginesatide was recalled a year later. In this study, 12 novel peptides were designed and synthesized by substituting specific amino acids of the monomeric peptide in peginesatide, with the aim of obtaining new EPO mimetic peptides with higher activities and lower side effects than the parent compound. Their cell proliferation activities were evaluated, and the structure-activity relationships were analyzed. Five compounds had equal cell proliferation activity to the control peptide. Among them, one compound showed a higher in vivo activity than the control peptide, with no obvious side effects.

Class I enveloped viruses share similarities in their apparent use of a hexameric coiled-coil assembly to drive the merging of virus and host cell membranes. Inhibition of coiled coil-mediated interactions using bioactive peptides that replicate an α-helical chain from the viral fusion machinery has significant antiviral potential. Here, we present the construction of a series of lipopeptides composed of a de novo heptad repeat sequence-based α-helical peptide plus a hydrocarbon tail. Promisingly, the constructs adopted stable α-helical conformations and exhibited relatively broad-spectrum antiviral activities against Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A viruses (IAVs). Together, these findings reveal a new strategy for relatively broad-spectrum antiviral drug discovery by relying on the tunability of the α-helical coiled-coil domains present in all class I fusion proteins and the amphiphilic nature of the individual helices from this multihelix motif.

DNA helix-based HIV-1 fusion inhibitors have been discovered as potent drug candidates. Introduction of hydrophobic groups to a nucleobase provides an opportunity to design inhibitors with novel structures and mechanisms of action. In this work, two novel nucleoside analogues (1 and 2) were synthesized and incorporated into four DNA duplex- and quadruplex-based inhibitors. All the molecules showed anti-HIV-1 fusion activity. The effect of the p-benzyloxyphenyl group and the attached linker on the helix formation and thermal stability were fully compared and discussed. Surface plasmon resonance analysis further indicated that inhibitors with the same DNA helix may still have variable reaction targets, mainly attributed to the different hydrophobic modifications.

Despite extensive investigations, the clinical translation of nanocarrier-based drug delivery systems (NDDS) for cancer therapy is hindered by inefficient delivery and poor tumor penetration. Conventional chemotherapy by administration of free small molecule anticancer drugs remains the standard of care for many cancers. Herein, other than for carrying and releasing drugs, small nanoparticles were used as a potentiator of conventional chemotherapy by co-administration with free chemotherapeutic agents. This strategy avoided the problems associated with drug loading and controlled release encountered in NDDS, and was also much simpler than NDDS. Negatively charged poly(amido amine)-2,3-dimethylmaleic monoamide (PAMAM-DMA) dendrimers were prepared, which possessed low toxicity and can be converted to positively charged PAMAM dendrimers responsive to tumor acidic pH. The in situ formed PAMAM in tumor tissue promoted cellular uptake of co-administered doxorubicin by increasing the cell membrane permeability, and subsequently enhanced the cytotoxicity of doxorubicin. The small size of the dendrimers was favorable for deep penetration in tumor. Co-injection of PAMAM-DMA with doxorubicin into nude mice bearing human tumors almost completely inhibited tumor growth, with a mean tumor weight reducing by 55.9% after the treatment compared with the treatment with doxorubicin alone.

The hexameric α-helical coiled-coil formed between the C-terminal and N-terminal heptad repeat (CHR and NHR) regions of class I viral fusion proteins plays an important role in mediating the fusion of the viral and cellular membranes and provides a clear starting point for molecular mimicry that drives viral fusion inhibitor design. Unfortunately, such peptide mimicry of the short α-helical region in the CHR of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein has been thwarted by the loss of the peptide's native α-helical conformation when taken out of the parent protein structure. Here, we describe that appropriate all-hydrocarbon stapling of the short helical portion-based peptide to reinforce its bioactive secondary structure remarkably improves antiviral potency. The resultant stapled peptide P21S10 could effectively inhibit infection by MERS-CoV pseudovirus and its spike protein-mediated cell-cell fusion; additionally, P21S10 exhibits improved pharmacokinetic properties than HR2P-M2, suggesting strong potential for development as an anti-MERS-CoV therapeutic.

This study presents the design and evaluation of a series of multifunctional peptides and their gene delivery abilities. The peptide sequences contained a cell-penetrating segment, six continuous histidine residues, a stearyl moiety and a laminin receptor-targeting segment. The YIGSR segment promoted cellular uptake through the interaction with laminin receptors on the surface of cells, which resulted in a great improvement in gene transfection efficiency. The conformation, particle size and zeta potential of peptide/DNA complexes were characterized via circular dichroism and dynamic light scattering. Their gene transfection efficiency was investigated by fluorescence-activated cell sorting and confocal microscopy. The transfection efficiency of the designed peptide vectors was higher than that of Lipo 2000. The peptide TAT-H6-K(C18)-YIGSR displayed transfection efficiencies at N/P ratios of 6, which was 3.5 and 7 times higher than that of Lipo 2000 in B16F10 and 293T cells, respectively. All peptides exhibited lower cytotoxicity than Lipo 2000 in B16F10 and 293T cells. In summary, the designed YIGSR-containing multifunctional peptide gene vectors promoted cellular uptake and gene transfection. Their in vivo transfection ability was investigated in zebrafish, and the transfection efficiency was determined by confocal microscopy and bioluminescence imaging. The peptide vectors, owing to their relatively short sequences and ease of functionalization, offer a promising approach for gene delivery because of their low cytotoxicity and high transfection efficiency.

Dynamic fluorescence patterns with variable output in response to external stimulus can make the current information storage technologies more flexible and intelligent. Yet it remains a great challenge to create such dynamic patterns because of the complicated synthesis process, high cost, limited stability, and biocompatibility of the functional fluorophores. Herein, a facile approach is presented for creating dynamic fluorescence patterns using the photodynamic surface chemistry based on disulfide bonds. By this method, high-resolution (≈20 µm) multicolor dynamic fluorescence patterns that are low-cost and dynamically rewritable can be easily fabricated using classical fluorophores such as fluorescein, rhodamine, and dansyl acid. Owing to the spatio-temporal controllability of light, the fluorescence patterns can be partly or entirely erased/rewritten on demand, and complex gray-level fluorescence images with increased information capacity can be easily generated. The obtained fluorescence patterns exhibit little changes after storing in air and solvent environments for 100 days, demonstrating their high stability. In addition, static patterns can also be created on the same disulfide surface using irreversible disulfide-ene chemistry, to selectively control the dynamicity of the generated fluorescence patterns. The authors show the successful application of this strategy on information protection and transformation.

Short peptide-based inhibition of fusion remains an attractive goal in antihuman immunodeficiency virus (HIV) research based on its potential for the development of technically and economically desirable antiviral agents. Herein, we report the use of the dithiol bisalkylation reaction to generate a series of

Steam accumulators are the only commercial solution for heat storage of direct steam generation (DSG) solar thermal power plants. Current accumulators have low storage capacity as the turbine suffers from inefficient off-design operation during heat discharge, thereby restricting the development of DSG technology. This work presents a novel approach to solving this problem by using two-stage accumulators and steam-organic Rankine cycles (RC-ORC). The system involves unique two-step heat discharge. Heat is initially released via water vaporization in a high temperature accumulator (HTA) to drive the RC-ORC, leading to an HTA temperature drop of approximately 30 °C. Water at a reduced temperature then flows from the HTA to a low temperature accumulator through a heat exchanger and the heat is used only to drive the ORC. Water temperature further drops by 130–190 °C. The fundamentals of the system are illustrated. A comparison with the conventional DSG system is conducted at a nominal power of 10 MW with an accumulator volume of 2500 m3. Thermodynamic performance of the system is investigated. The equivalent payback period ( EPP ) regarding the use of the second step heat discharge is estimated. Results indicate that the second step heat discharge can increase the storage capacity by 460%, with an EPP of less than 5 years in most cases. Overall, the proposed solution improves the cost-effectiveness of the DSG system.

Novel water-soluble paclitaxel prodrugs were designed and synthesized by introducing morpholino groups through different linkers. These derivatives showed 400-20,000-times greater water solubility than paclitaxel as well as comparable activity in MCF-7 and HeLa cell lines. The prodrug PM4 was tested in the S-180 tumor mouse model, with paclitaxel as the positive control. The results showed that PM4 had comparable antitumor activity as paclitaxel, with tumor inhibition of 54% versus 56%, and remarkably decreased toxicity. The survival rate of treated mice was 8/8 in the PM4 group, compared to 3/8 in the paclitaxel group.

Short circulation is a disadvantage of dendrimers as drug delivery carriers due to their small size. In this work, pH-sensitive morpholino-terminated generation 5 poly(amido amine) (PAMAM) is prepared. At neutral pH, the dendrimer has a hydrophilic neutral surface and thereby stealth property. Under tumor acidic environments, the dendrimer develops positive charges due to protonation of the morpholino groups, and cellular uptake of the dendrimer is subsequently enhanced. The dendrimer is predicted to penetrate deeper within the tumor due to its small size (∼9 nm), and thereby the pH-sensitive function can be efficiently achieved because the microenvironment in the deeper sites is more acidic. Moreover, the morpholino-terminated PAMAM exhibited longer in vivo circulation time compared to PAMAM and hydroxyl-terminated PAMAM, partly compensating for the disadvantage of short circulation of dendrimers. Furthermore, the morpholino-terminated PAMAM also showed lower cytotoxicity than PAMAM and hydroxyl-terminated PAMAM.

Lengthy peptides corresponding to the C-terminal heptad repeat (C-peptides) of human immunodeficiency virus type 1 (HIV-1) gp41 are potent inhibitors against virus-cell fusion. Designing short C-peptide-based HIV-1 fusion inhibitors could potentially redress the physicochemical and technical liabilities of a long-peptide therapeutic. However, designing such inhibitors with high potency has been challenging. We generated a conjugated architecture by incorporating small-molecule inhibitors of gp41 into the N-terminus of a panel of truncated C-peptides. Among these small molecule-capped short peptides, the 26-residue peptide Indole-T26 inhibited HIV-1 Env-mediated cell-cell fusion and viral replication at low nanomolar levels, reaching the potency of the only clinically used 36-residue peptide T20 (enfuvirtide). Collectively, our work opens up a new avenue for developing short peptide-based HIV-1 fusion inhibitors, and may have broad applicability to the development of modulators of other class I fusion proteins.

We report an efficient strategy to recapitulate NHR α-helical trimers in the HIV-1 membrane fusion protein as promising antiviral therapeutics., Sequestering peptides derived from the N-terminal heptad repeat (NHR) of class I viral fusion proteins into a non-aggregating trimeric coiled-coil conformation remains a major challenge. Here, we implemented a synthetic strategy to stabilize NHR-helical trimers, with the human immunodeficiency virus type 1 (HIV-1) gp41 fusion protein as the initial focus. A set of trimeric scaffolds was realized in a synthetic gp41 NHR-derived peptide sequence by relying on the tractability of coiled-coil structures and an additional isopeptide bridge-tethering strategy. Among them, (N36M)3 folded as a highly stable helical trimer and exhibited promising inhibitory activity against HIV-1 infection, exceptional resistance to proteolysis, and effective native ligand-binding capability. We anticipate that the trimeric coiled-coil recapitulation methodology described herein may have broader applicability to yield NHR trimers of other class I enveloped viruses and to prepare helical tertiary structure mimetics of certain natural protein–protein interactions for biomedical applications.

Addition polymerization usually results in polymers with long carbon-carbon main chains. Cyanoacrylate (CA) is arguably an important example of such polymerization and has gained widespread acceptance as an all-purpose adhesive. However, CA-based medical adhesives have never been approved by the U.S. Federal Drug Administration for use below the skin, mainly due to the low biodegradability and biocompatibility of their solid glue after polymerization. In this research, a cross-linking strategy involving the combination of alkyl-CA and the cross-linking agent poly(ethylene glycol)-di(cyanoacrylate) (CA-PEG-CA) to form a copolymeric network was used to synthesize a new generation of biodegradable CA medical adhesives. The degradability could be modulated by adjusting the ratio of CA-PEG-CA to alkyl-CA and the length of PEG. An optimal composite adhesive, LKJ11, was shown to have excellent biodegradability, adhesive capability, and biocompatibility. Importantly, the molecular weight of polycyanoacrylate chains in the polymerized LKJ11 was greatly reduced compared to those polymerized from pure butyl-CA. Thus, the degradation product could be readily extracted. The results showed that LKJ11 represents a new generation of CA-based biodegradable medical adhesives. This advance also provides a general strategy to facilitate the conversion of other polymers with long carbon-carbon main chains to a biodegradable form, thereby expanding the novel applications available for traditional polymeric materials.

DNA helix–based HIV-1 fusion inhibitors have been discovered as potent drug candidates, but further research is required to enhance their efficiency. The trimeric structure of the HIV-1 envelope glycoprotein provides a structural basis for multivalent drug design. In this work, a “multi-domain” strategy was adopted for design of an oligodeoxynucleotide with assembly, linkage, and activity domains. Built on the self-assembly of higher-order nucleic acid structure, a novel category of multivalent DNA helix–based HIV-1 fusion inhibitor could be easily obtained by a simple annealing course in solution buffer, with no other chemical synthesis for multivalent connection. An optimized multivalent molecule, M4, showed significantly higher anti–HIV-1 fusion activity than did corresponding monovalent inhibitors. Examination of the underlying mechanism indicated that M4 could interact with HIV-1 glycoproteins gp120 and gp41, thereby inhibiting 6HB formation in the fusion course. M4 also showed anti-RDDP and anti-RNase H activity of reverse transcriptase. Besides, these assembled molecules showed improved in vitro metabolic stability in liver homogenate, kidney homogenate, and rat plasma. Moreover, little acute toxicity was observed. Our findings aid in the structural design and understanding of the mechanisms of DNA helix–based HIV-1 inhibitors. This study also provides a general strategy based on a new structural paradigm for the design of other multivalent nucleic acid drugs.

We designed a series of peptide vectors that contain functional fragments with the goal of enhancing cellular internalization and gene transfection efficiency. The functional fragments included a cell-penetrating peptide (R9), a cationic amphiphilic α-helical peptide [(LLKK)3-H6 or (LLHH)3], a stearyl moiety, and cysteine residues. Vectors were also synthesized with D-type amino acids to improve their proteolytic stability. The conformations, particle sizes, and zeta potentials for complexes of these peptides with pGL3 plasmid DNA were characterized by circular dichroism and dynamic light scattering. In addition, cellular uptake of the peptide/DNA complexes and gene transfection efficiency were investigated with fluorescence-activated cell sorting and confocal laser-scanning microscopy. Greater transfection efficiency was achieved with the vectors containing the R9 segment, and the efficiency was greater than Lipo2000. In addition, the D-type C18-c(llkk)3ch6-r9 had about 7 times and 5.5 times the transfection efficiency of Lipo2000 in 293T cells and NIH-3T3 cells at the N/P ratio of 6, respectively. Overall, the multifunctional peptide gene vectors containing the R9 segment exhibited enhanced cellular internalization, a high gene transfection efficiency, and low cytotoxicity.

In this study, a multilayer coating technology would be adopted to prepare a porous composite scaffold and the growth factor release and ultrasound techniques were introduced into bone tissue engineering to finally solve the problems of vascularization and bone formation in the scaffold whilst the designed multilayer composite with gradient degradation characteristics in the space was used to match the new bone growth process better. The results of animal experiments showed that the use of low intensity pulsed ultrasound (LIPUS) combined with growth factors demonstrated excellent capabilities and advantages in both vascularization and new bone formation in bone tissue engineering. The degradation of the used scaffold materials could match new bone formation very well. The results also showed that only RGD-promoted cell adhesion was insufficient to satisfy the needs of new bone formation while growth factors and LIPUS stimulation were the key factors in new bone formation.

DNA triplexes with hydrophobic modifications were designed and evaluated for their activity as inhibitors of the cell fusion of human immunodeficiency virus type 1 (HIV-1). Triplex inhibitors displayed low micromolar activities in the cell–cell fusion assay and nanomolar activities in the anti-HIV-1 pseudovirus test. Helix structure and the presence of sufficient numbers of hydrophobic regions were essential for the antifusion activity. Results from native polyacrylamide gel electrophoresis and a fluorescent resonance energy transfer-based inhibitory assay indicated that these triplexes may interact with the primary pocket at the glycoprotein 41 (gp41) N-heptad repeat, thereby inhibiting formation of the HIV-1 gp41 6-helical bundle. Triplex-based complexes may represent a novel category of HIV-1 inhibitors in anti-HIV-1 drug discovery.