Optimization of Dendritic Polypeptide Delivery System for Antisense Antibacterial Agents Targeting ftsZ.

There is an urgent requirement for a novel treatment strategy for drug-resistant Staphylococcus aureus (S. aureus) infection. Antisense antimicrobials are promising antimicrobials, and efficient drug delivery systems are necessary for the further development of antisense antimicrobials. To develop new antisense drugs and further improve delivery efficiency and safety, we designed and screened new antisense sequences and optimized dendritic polypeptide nanoparticles (DP-AD) discovered in previous studies. The N/P ratio is optimized from 8:1 to 6:1, and the positive charge number of the optimized DP-AD is studied comprehensively. The results show that the N/P ratio and positive charge number have no significant effect on the particle size distribution and transport efficiency of DP-AD. Reducing the N/P ratio can significantly reduce the cytotoxicity of DP-AD, but it does not affect its delivery efficiency and antibacterial activity. However, in drug-resistant strains, the antibacterial activity of DP-AD76:1 with 10 positive charges is higher than that of DP-AD86:1 with 8 positive charges. Our research discovered a novel ASOs targeting ftsZ and concluded that DP-AD76:1 with 10 positive charges was the optimal choice at the current stage, which provided a promising strategy for the treatment of drug-resistant S. aureus.

The complete chloroplast genome of Chloranthus nervosus Collett ex Hemsl. 1890 (Chloranthaceae).

In this study, we sequenced and assembled the complete chloroplast genome of Chloranthus nervosus Collett ex Hemsl. 1890. The total length of the complete chloroplast sequence was found to be 158,002 bp. It consisted of a large single-copy (LSC) region of 87,127 bp, a small single-copy (SSC) region of 18,541 bp, and a pair of inverted repeat (IR) regions, each with a length of 26,167 bp. The overall GC content of the complete chloroplast genome was 38.9%, with the LSC region, SSC region, and IR regions exhibiting GC contents of 37.4%, 34.1%, and 43.1%, respectively. The annotation of the chloroplast genome revealed a total of 131 genes, comprising 86 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis revealed that the seven sampled species of Chloranthus were divided into two clades. Within the clade characterized by long filamentous anther connectives, C. nervosus showed the closest relation to C. japonicus. These findings validated the previous preliminary results on the phylogenetic relationships of the seven species of Chloranthus with strong support.

Nanoarchitectured Graphene Organic Framework for Drug Delivery and Chemo-photothermal Synergistic Therapy.

The combination of phototherapy and chemotherapy has received extensive attention in the field of cancer therapy. Hence, graphene organic framework (GOF) with a large d-spacing was prepared by solvothermal method, and a novel nanocomposite based on bovine serum albumin (BSA) and the anticancer drug doxorubicin (DOX) was developed, which effectively achieved a photothermal-chemotherapy synergistic treatment. When the feeding ratio was 1:1.6, the DOX loading capacity was 18.51%, and the GOF-BSA/DOX nanocomposite possessed unobvious pH response characteristic, as well as the cumulative release of DOX reached 54.17% at 42°C in the acidic environment (pH = 5.0). The nanocarriers also showed excellent photothermal property and photothermal stability in vitro. In addition, under 808 nm near-infrared laser (NIR) irradiation, the GOF-BSA/DOX nanocomposites generated a large amount of heat, which significantly enhanced the synergistic antitumor effect of in vitro photothermal-chemotherapy. Furthermore, the GOF-BSA/DOX nanocomposites exhibited significantly increased cytotoxicity in the NIR compared with chemotherapy or photothermal therapy alone, suggesting that the combination of chemotherapy and photothermal therapy has excellent antitumor capacity. Therefore, porous GOF nanocarriers may have great potential in combined anti-tumour therapy.

Optical tweezers and Raman spectroscopy for single-cell classification of drug resistance in acute lymphoblastic leukemia.

Laser Tweezers Raman Spectroscopy (LTRS) is a combination of laser tweezers and Raman spectroscopy. It is a physical tool based on the mechanical effects of the laser, which can be used to study single living cells in suspension in a fast and non-destructive way. Our work aims to establish a methodology system based on LTRS to rapidly and non-destructively detect the resistance of acute lymphoblastic leukemia (ALL) cells and to provide a new idea for the evaluation of the resistance of ALL cells. Two specific adriamycin-resistant and parental ALL cells BALL-1 and Nalm6 were included in this study. Adriamycin resistant cells can induce the spectral differences, which can be detected by LTRS initially. To ensure the accuracy of the results, we use the principal components analysis (PCA) as well as the classification and regression trees (CRT) algorithms, which show that the specificity and sensitivity of LTRS are above 90%. In addition, to further clarify the chemoresistance status of ALL cells, we used the CRT models and receiver operating characteristic (ROC) curves which are based on the band data to look for some important bands and band intensity ratios that have strong pointing significance. Our work proves that LTRS analysis combined with multivariate statistical analyses have great potential to be a novel analytical strategy at the single-cell level for rapidly evaluating the chemoresistance status of ALL cells.

Connectome-based prediction of marital quality in husbands' processing of spousal interactions.

Marital quality may decrease during the early years of marriage. Establishing models predicting individualized marital quality may help develop timely and effective interventions to maintain or improve marital quality. Given that marital interactions have an important impact on marital well-being cross-sectionally and prospectively, neural responses during marital interactions may provide insight into neural bases underlying marital well-being. The current study applies connectome-based predictive modeling, a recently developed machine-learning approach, to functional magnetic resonance imaging (fMRI) data from both partners of 25 early-stage Chinese couples to examine whether an individual's unique pattern of brain functional connectivity (FC) when responding to spousal interactive behaviors can reliably predict their own and their partners' marital quality after 13 months. Results revealed that husbands' FC involving multiple large networks, when responding to their spousal interactive behaviors, significantly predicted their own and their wives' marital quality, and this predictability showed gender specificity. Brain connectivity patterns responding to general emotional stimuli and during the resting state were not significantly predictive. This study demonstrates that husbands' differences in large-scale neural networks during marital interactions may contribute to their variability in marital quality and highlights gender-related differences. The findings lay a foundation for identifying reliable neuroimaging biomarkers for developing interventions for marital quality early in marriages.

A biodegradable multifunctional nanoplatform based on antimonene nanosheets for synergistic cancer phototherapy and dual imaging.

Recently, nanomaterials have been well-studied in cancer therapy, but some of them often experience difficulties with degradation in vivo, which could cause severe damage to the human body. Among numerous biodegradable nanomaterials, antimonene nanosheets (AMNSs) are versatile, and possess photothermal and photodynamic properties and photoacoustic imaging (PAI) and drug loading ability. Herein, we employed a clearable multifunctional system. The small molecule photosensitizer IR820 and the gold nanoparticles (AuNPs) at small sizes of approximately 5 nm were loaded onto AMNSs coated with biodegradable chitosan (CS). This nanoplatform showed excellent photothermal and photodynamic properties, satisfactory degradability and photoacoustic imaging ability, good biocompatibility and effective NIR light triggered intracellular synergistic treatment. It also displayed good fluorescence imaging ability in the experiment of cell uptake. These suggested that this versatile nanoplatform was able to significantly enhance the therapeutic efficiency based on synergistic phototherapy, and could also be applied in fluorescence and photoacoustic dual imaging for integrating diagnosis and treatment.

Efficient Brain Connectivity Reconfiguration Predicts Higher Marital Quality and Lower Depression.

Social-information processing is important for successful romantic relationships and protecting against depression, and depends on functional connectivity (FC) within and between large-scale networks. Functional architecture evident at rest is adaptively reconfigured during task and there were two possible associations between brain reconfiguration and behavioral performance during neurocognitive tasks (efficiency effect and distraction-based effect). This study examined relationships between brain reconfiguration during social-information processing and relationship-specific and more general social outcomes in marriage. Resting-state FC was compared with FC during social-information processing (watching relationship-specific and general emotional stimuli) of 29 heterosexual couples, and the FC similarity (reconfiguration efficiency) was examined in relation to marital quality and depression 13 months later. The results indicated wives' reconfiguration efficiency (globally and in visual association network) during relationship-specific stimuli processing was related to their own marital quality. Higher reconfiguration efficiency (globally and in medial frontal, frontal-parietal, default mode, motor/sensory and salience networks) in wives during general emotional stimuli processing was related to their lower depression. These findings suggest efficiency effects on social outcomes during social cognition, especially among married women. The efficiency effects on relationship-specific and more general outcome are respectively higher during relationship-specific stimuli or general emotional stimuli processing.

Characterization of Drug Resistance in Chronic Myeloid Leukemia Cells Based on Laser Tweezers Raman Spectroscopy.

Multidrug resistance is highly associated with poor prognosis of chronic myeloid leukemia. This work aims to explore whether the laser tweezers Raman spectroscopy (LTRS) could be practical in separating adriamycin-resistant chronic myeloid leukemia cells K562/adriamycin from its parental cells K562, and to explore the potential mechanisms. Detection of LTRS initially reflected the spectral differences caused by chemoresistance including bands assigned to carbohydrates, amino acid, protein, lipids, and nucleic acid. In addition, principal components analysis as well as the classification and regression trees algorithms showed that the specificity and sensitivity were above 90%. Moreover, the band data-based classification and regression tree model and receiver operating characteristic curve further determined some important bands and band intensity ratios to be reliable indexes in discriminating K562 chemoresistance status. Finally, we highlighted three metabolism pathways correlated with chemoresistance. This work demonstrates that the label-free LTRS analysis combined with multivariate statistical analyses have great potential to be a novel analytical strategy at the single-cell level for rapid evaluation of the chemoresistance status of K562 cells.

ICG/5-Fu coencapsulated temperature stimulus response nanogel drug delivery platform for chemo-photothermal/photodynamic synergetic therapy.

The multiple diagnosis and treatment mechanisms of chemotherapy combined with photothermal/photodynamic therapy have very large application prospects in the field of cancer treatment. Therefore, in order to achieve effective and safe antitumour treatment, it is necessary to design an intelligent responsive polymer nanoplatform as a drug delivery system. Herein, the thermosensitive poly-N-isopropylacrylamide (PNIPAM) nanogel particles were prepared by soap-free emulsion polymerization and loaded with a large amount of photosensitizer indocyanine green (ICG) and anticarcinogen 5-fluorouracil (5-Fu), which effectively to realize the cooperative chemotherapy and photothermal/photodynamic therapy for tumours. The 5-Fu@ICG-PNIPAM nanogels significantly improved the bioavailability of the drug and achieved controlled release. In addition, under near-infrared laser (NIR) irradiation at 808 nm, 5-Fu@ICG-PNIPAM nanogels generated lots of heat and reactive oxygen, which significantly enhanced cellular uptake and in vitro antitumour treatment effects. The results showed that 5-Fu@ICG-PNIPAM nanogels were effectively endocytosed by HeLa cells, which also enhanced the drug's entrance into the nucleus. Moreover, compared with alone chemotherapy or photothermal/photodynamic therapy, 5-Fu@ICG-PNIPAM nanogels significantly increased cytotoxicity under NIR irradiation, suggesting that chemotherapy and photothermal/photodynamic synergistic therapy had excellent antitumour properties. Therefore, this temperature-responsive nanogel platform probably has great application prospects in clinical antitumour treatment.

Versatile Nanoplatform Loaded with Doxorubicin and Graphene Quantum Dots/Methylene Blue for Drug Delivery and Chemophotothermal/Photodynamic Synergetic Cancer Therapy.

A versatile platform for nanodrug delivery and synergetic therapy is a promising therapeutic pattern for antitumor treatment in clinical biology. Here, we innovatively encapsulated graphene quantum dots (GQDs) or methylene blue (MB) together with doxorubicin (DOX) into the cores of poly lactic-co-glycolic acid (PLGA) nanoparticles coated with bovine serum albumin (BSA) based on the emulsion method to synthesize core-shell structure nanoparticles (GQDs@DOX/PB and MB@DOX/PB NPs). The GQDs@DOX/PB NPs exhibited excellent photothermal properties and stability under 808 nm laser irradiation. The in vitro chemophotothermal synergetic experiments manifested that the GQDs@DOX/PB NPs effectively cause the thermal ablation of tumor cells under NIR laser irradiation. Meanwhile, the in vitro chemophotodynamic synergetic experiments revealed that the MB@DOX/PB NPs could produce reactive oxygen species and showed outstanding antitumor efficacy under 660 nm laser irradiation. Consequently, the pH-responsive multifunctional nanoparticles prepared by a facile strategy have a high tumor cell-killing efficacy, manifesting excellent potential in synergistic therapy.

Antioxidant synergistic effects of Osmanthus fragrans flowers with green tea and their major contributed antioxidant compounds.

The antioxidant synergistic effects of Osmanthus fragrans flowers with green tea were evaluated, and their major antioxidant compounds contributed to the total amount of synergy were determined. The antioxidant compounds in O. fragrans flowers with green tea were identified by LC-MS and quantified by UPLC-PDA. The synergistic antioxidant interactions between O. fragrans flowers with green tea and their antioxidant compounds were tested using the Prieto's model after the simulated digestion. The main antioxidant compounds in O. fragrans flowers were acteoside and salideroside, whereas the main antioxidant compounds in green tea were caffeine, gallic acid, and L-epicatechin. The significant synergistic effect between O. fragrans flowers and green tea was observed and among nearly all of the combinations of their antioxidant compounds. Among the combinations, acteoside and gallic acid contributed most to the antioxidant synergy between O. fragrans flowers and green tea. However, the simulated digestion decreased this antioxidant synergy because it reduced the contents and the antioxidant capacities of their compounds, as well as the antioxidant synergy among the compounds.