Protein-Based Biological Materials: Molecular Design and Artificial Production.

Polymeric materials produced from fossil fuels have been intimately linked to the development of industrial activities in the 20th century and, consequently, to the transformation of our way of living. While this has brought many benefits, the fabrication and disposal of these materials is bringing enormous sustainable challenges. Thus, materials that are produced in a more sustainable fashion and whose degradation products are harmless to the environment are urgently needed. Natural biopolymers─which can compete with and sometimes surpass the performance of synthetic polymers─provide a great source of inspiration. They are made of natural chemicals, under benign environmental conditions, and their degradation products are harmless. Before these materials can be synthetically replicated, it is essential to elucidate their chemical design and biofabrication. For protein-based materials, this means obtaining the complete sequences of the proteinaceous building blocks, a task that historically took decades of research. Thus, we start this review with a historical perspective on early efforts to obtain the primary sequences of load-bearing proteins, followed by the latest developments in sequencing and proteomic technologies that have greatly accelerated sequencing of extracellular proteins. Next, four main classes of protein materials are presented, namely fibrous materials, bioelastomers exhibiting high reversible deformability, hard bulk materials, and biological adhesives. In each class, we focus on the design at the primary and secondary structure levels and discuss their interplays with the mechanical response. We finally discuss earlier and the latest research to artificially produce protein-based materials using biotechnology and synthetic biology, including current developments by start-up companies to scale-up the production of proteinaceous materials in an economically viable manner.

RhRu Alloy-Anchored MXene Nanozyme for Synergistic Osteosarcoma Therapy.

Noble metal nanozymes hold promise in cancer therapy due to adjustable enzyme-like activities, unique physicochemical properties, etc. But catalytic activities of monometallic nanozyme are confined. In this study, 2D titanium carbide (Ti3 C2 Tx )-supported RhRu alloy nanoclusters (RhRu/Ti3 C2 Tx ) are prepared by a hydrothermal method and utilized for synergistic therapy of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) on osteosarcoma. The nanoclusters are small in size (3.6 nm), uniform in distribution, and have excellent catalase (CAT) and peroxidase (POD)-like activities. Density functional theory calculations show that there is a significant electron transfer interaction between RhRu and Ti3 C2 Tx , which has strong adsorption to H2 O2 and is beneficial to enhance the enzyme-like activity. Furthermore, RhRu/Ti3 C2 Tx nanozyme acts as both PTT agent for converting light into heat, and photosensitizer for catalyzing O2 to 1 O2 . With the NIR-reinforced POD- and CAT-like activity, excellent photothermal and photodynamic performance, the synergistic CDT/PDT/PTT effect of RhRu/Ti3 C2 Tx on osteosarcoma is verified by in vitro and in vivo experiments. This study is expected to provide a new research direction for the treatment of osteosarcoma and other tumors.

Research on the intrinsic mechanism of the darkening of liquid foundation.

BACKGROUND: To investigate the intrinsic mechanism that causes the darkening of liquid foundations. MATERIALS AND METHOD: A total of 36 commercial liquid foundations were firstly studied for preliminary screening of influencing factors. A basic liquid foundation was developed for controlling variables to study the influence of each single factor. These samples were evenly spread on the standard opacity charts with the thickness of 100 µm and applied onto human inner forearm skin with the dosage of 2 mg/cm2 . The discoloration of each sample was continuously recorded using spectrophotometers and reported in the CIE 1976 L*a*b* color space for at least 120 min, and ΔE was calculated to describe the severity of darkening. RESULTS: One hundred twenty-minute ΔE of all commercial foundations was highly negatively correlated with their 120-min ΔITA° (R2  = 0.88, p < 0.01). A strong positive correlation was found between the severity of darkening and the volatilization of the basic foundations (R2  = 0.83, p < 0.01). And the darkening of silicone-based basic foundations using pigment coating with silicon is weaker than those without silicon (p < 0.05). CONCLUSION: The process of the discoloration of liquid foundation is accompanied by the decrease of ITA° and manifested as darkening. The volatilization rate of the product and the coating method of the pigments used in the formula can noticeably affect the darkening of the liquid foundation.

First Report of Colletotrichum gloeosporioides Causing Anthracnose on Peanut in Chongqing, China.

In July 2022, dieback and discoloration were detected on infected stems of peanut in Qijiang District of Chongqing (106.56°E,29.41°N), China, with an incidence up to 5%. These peanut stems had disease symptoms typical of anthracnose with irregular gray-brown spots with dark brown edges, sunken, and necrotic. High temperature and high humidity were favorable for the growth of the pathogen. To isolate the pathogen, we collected 10 typical infected peanuts and cut one piece from each of symptomatic stems, surface sterilized with 0.5% NaClO for 1 min, and 75% ethanol for 30 s, then rinsed three times with sterile distilled water and dried on sterilized filter paper. These pieces were incubated on potato dextrose agar (PDA) at 25°C in the dark. Pure cultures were obtained from hyphal tips of each colony. It was found that isolates with the same colony morphology were isolated from each infected stem. A representative isolate (L7) was used for morphological characterization, molecular analysis, phylogenetic analysis, and pathogenicity tests. The colonies appeared white to gray, with white margins and aerial hyphae, and the reverse of the colonies was gray to brown. Conidia were cylindrical, aseptate, with obtuse to slightly rounded ends, 13.4 to 18.8 × 4.2 to 5.8 µm (n=50). Morphological characteristics were generally consistent with those of Colletotrichum gloeosporioides species complex (Cannon et al., 2012). For molecular identification, genomic DNA was extracted using a CTAB method and partial sequences of ß-tubulin (TUB2), actin (ACT) genes, chitin synthase (CHS) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were amplified and sequenced using primers T1/T2, ACT-512F/ACT-783R, CHS-79F/CHS-345R, and GDF1/GDR1, respectively (Damm et al., 2012; Dowling et al., 2020). Using the BLAST, TUB2, ACT, CHS and GAPDH gene sequences (GenBank accession No. OR714793, OP168707, OP168708 and OR714794, respectively) were100% (429 bp out of 429 bp), 99.22% (256 bp out of 258 bp), 99.64% (276 bp out of 277 bp) and 100% (253 bp out of 253 bp) identical to C. gloeosporioides CBS:112999 (JQ005587, JQ005500, JQ005326, and JQ005239), respectively. Using Neighbor-Joining algorithm, phylogenetic analysis was conducted based on the concatenated sequences of published TUB2, ACT, CHS and GAPDH genes. The identified isolate (L7) was closely related to C. gloeosporioides. To evaluate pathogenicity, the stems of ten peanut (Zhonghua12) seedlings (2 weeks) were wounded with a sterile toothpick and mycelial plugs (5 mm in diameter) or 20 µl of conidial suspension (105/ml) were inoculated. Non-colonized agar plugs or 20 µl of sterile distilled water were treated as control. After inoculation, the peanuts were kept in a moist chamber at 28°C with 80% humidity in the dark for 24 h, and subsequently transferred to the moist chamber with 12 h light and darkness cycle for 6 days, similar symptoms were observed on all inoculated peanuts. Controls remained asymptomatic. C. gloeosporioides was reisolated from the diseased stems and confirmed using morphological features and sequence analysis of TUB2, ACT, CHS and GAPDH. Anthracnose caused by C. truncatum and C. fructicola has been reported on peanut leaves in China (Gong et al., 2023; Yu et al., 2019). To our knowledge, this is the first report of anthracnose on peanut stem caused by C. gloeosporioides in Chongqing. Our report will provide crucial information for studying on epidemiology and management of this disease.

Exploring the mechanism associated with methane emissions during composting: Inoculation with lignocellulose-degrading microorganisms.

Inoculation with microorganisms is an effective strategy for improving traditional composting processes. This study explored the effects of inoculation with lignocellulose-degrading microorganisms (LDM) on the degradation of organic matter (OM), methane (CH4) emissions, and the microbial community (bacteria and methanogens) during composting. The results showed that LDM accelerated the degradation of OM (including the lignocellulose fraction) and increased the CH4 releases in the later thermophilic and cooling stages during composting. At the ending of composting, LDM increased the CH4 emissions by 38.6% compared with the control. Moreover, LDM significantly increased the abundances of members of the bacterial and methanogenic community during the later thermophilic period (P < 0.05). In addition, LDM promoted the growth and activity of major bacterial genera (e.g., Ureibacillus) with the ability to degrade macromolecular OM, as well as affecting key methanogens (e.g., Methanocorpusculum) in the composting system. Network analysis and variance partitioning analysis indicated that OM and temperature were the main factors that affected the bacterial and methanogen community structures. Structural equation modeling demonstrated that the higher CH4 emissions under LDM were related to the growth of methanogens, which was facilitated by the anaerobic environment produced by large amounts of CO2. Thus, aerobic conditions should be improved during the end of the thermophilic and cooling composting period when inoculating with lignocellulose-degrading microorganisms in order to reduce CH4 emissions.

[Screening of quality markers and activity verification of Glycyrrhizae Radix et Rhizoma based on small molecule compound-protein interaction].

In order to solve the problem of weak correlation between quality control components and efficacy of Glycyrrhizae Radix et Rhizoma, this study detected the interaction between small molecular chemical components of Glycyrrhizae Radix et Rhizoma and total proteins of various organs of mice by fluorescence quenching method to screen potential active components. The 27 chemical components in Glycyrrhizae Radix et Rhizoma were detected by HPLC and their deletion rates in 34 batches of Glycyrrhizae Radix et Rhizoma were calculated. Combined with the principle of component effectiveness and measurability, the potential quality markers(Q-markers) of Glycyrrhizae Radix et Rhizoma were screened. RAW264.7 macrophage injury model was induced by microplastics. The cell viability and nitric oxide content were detected by CCK-8 and Griess methods. The levels of inflammatory factors(TNF-α, IL-1ß, IL-6, CRP) and oxidative stress markers(SOD, MDA, GSH) were detected by the ELISA method to verify the activity of Q-markers. It was found that the interaction strength between different chemical components and organ proteins in Glycyrrhizae Radix et Rhizoma was different, reflecting different organ selectivity and 18 active components were screened out. Combined with the signal-to-noise ratio of the HPLC chromatographic peaks and between-run stability of the components, seven chemical components such as liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and ammonium glycyrrhizinate were finally screened as potential Q-markers of Glycyrrhizae Radix et Rhizoma. In vitro experiments showed that Q-markers of Glycyrrhizae Radix et Rhizoma could dose-dependently alleviate RAW264.7 cell damage induced by microplastics, inhibit the secretion of inflammatory factors, and reduce oxidative stress. Under the same total dose, the combination of various chemical components could synergistically enhance anti-inflammatory and antioxidant effects compared with the single use. This study identified Q-markers related to the anti-inflammatory and antioxidant effects of Glycyrrhizae Radix et Rhizoma, which can provide a reference for improving the quality control standards of Glycyrrhizae Radix et Rhizoma.

Super-Hydrophilic Zwitterionic Polymer Surface Modification Facilitates Liquid Transportation of Microfluidic Sweat Sensors.

The transportation of sweat in an epidermal sweat sensor is critical for the monitoring of biochemical compositions of human sweat. However, it is still a challenge to engineer microfluidic devices with super-wetting channels for such epidermal sweat sensors. Herein, a zwitterionic poly (2-methacryloyloxyethyl phosphorylcholine) (PMPC) modified microfluidic device with super-wetting and good liquid transport ability via an azo coupling reaction of PMPC onto the surface of polydimethylsiloxane microfluidic devices is reported. The obtained PMPC-modified microfluidic device can be integrated with flexible electrochemical sensor to measure the ion compositions of human sweat in real-time. The super-hydrophilic zwitterionic polymer surface modification can greatly facilitate the transportation of body fluids in microfluidic sensors for the detection of various biomarkers. Such microfluidic sensors have great potential for next-generation personalized healthcare.

Physiological and Transcriptional Analysis Reveals the Response Mechanism of Camellia vietnamensis Huang to Drought Stress.

Drought stress is considered the main obstacle restricting Camellia vietnamensis Huang (C. vietnamensis) yield. Hainan is the southernmost distribution region of C. vietnamensis in China and experiences a drought period annually. To study the drought-stress-response mechanism of C. vietnamensis, we treated seedlings of drought-tolerant (HD1) and drought-sensitive (WH1) cultivars with PEG-6000 (PEG) to simulate drought stress and compared the physiology and transcriptome of their leaves at 0 d, 3 d and 6 d posttreatment. Under drought stress, the growth of C. vietnamensis was inhibited, the relative water content (RWC) of leaves decreased and the contents of malondialdehyde (MDA), antioxidant enzyme activities, osmotic regulatory substances and secondary metabolites increased. Compared with those of WH1, the leaf RWC, osmotic-regulation substance content (proline, soluble protein and soluble sugar) and antioxidant enzyme activity (superoxide dismutase, peroxidase and catalase) of HD1 were significantly increased, while the relative electrical conductivity and MDA content were significantly decreased. Compared with WH1, 2812, 2070 and 919, differentially expressed genes (DEGs) were detected in HD1 0 d, 3 d and 6 d posttreatment, respectively, and the number of DEGs increased with increasing treatment time. The detected DEGs are involved in the drought stress response of C. vietnamensis mainly through plant-hormone signal transduction and lignin and flavonoid biosynthesis pathways. Drought stress significantly activated the expression of several lignin and flavonoid biosynthesis genes in HD1. Moreover, total flavonoid and total polyphenol contents in HD1 were significantly increased, suggesting that the accumulation of flavonoids may be a key factor in the drought stress response of C. vietnamensis. Additionally, 191 DEGs were associated with coding transcription factors (TFs). This study provides insight into the molecular mechanism of the drought stress response of C. vietnamensis and provides a theoretical basis for the development and cultivation of new drought-resistant cultivars.

Mechanism analysis of the immobilization of heavy metal ions with the water-soluble polymer: The influence of resin structure and the further adsorption of chelate.

Polymer materials have become one of the potential materials for remediation of heavy metal (HM) contamination in water and soil. However, the specific advantages of polymers are rarely studied. Water-soluble thiourea formaldehyde resin (WTF) is one of the effective polymer amendments. Through leaching experiments, WTF can stabilize 93.0% of Cd2+ and 99.7% of Cu2+. The results of HM morphology analysis show that after adding WTF, most of the HMs have been transformed into a relatively stable state. For example, in the process of remediation of 6 mg/kg Cd contaminated soil, the proportion of acid-soluble Cd decreased from 56.5% to 12.8%, and the residual state increased from 13.5% to 45.4%. Compared with the resin-free structure, the three-dimensional structure of the resin plays an important role, but the efficiency of precipitation with HMs is doubled. According to the simulation of the adsorption process by Materials Studio, the characterization of the scanning electron microscope-energy dispersive instrument and the results of the adsorption experiment, in the solution, the precipitate formed by WTF and Cd2+ has multilayer adsorption of HMs, and can further adsorb HM by -OH. Soil enzyme activity experiments proved that the risk of secondary pollution by adding WTF is rare, and even WTF can achieve the effect of slow-release nitrogen fertilizer. In the WTF remediation process, the biological toxicity reduction of HMs is result from, on the one hand, the complexation of functional group of WTF; on the other hand, the resin structure of WTF; in addition, multi-layer adsorption and adsorption of end groups in the precipitation formed by WTF and HM. This work provides a theoretical basis for the potential capabilities of water-soluble resins and is beneficial to the design and development of subsequent amendments.

Nanometer-Scale Force Profiles of Short Single- and Double-Stranded DNA Molecules on a Gold Surface Measured Using a Surface Forces Apparatus.

Using a surface forces apparatus (SFA), we have studied the nanomechanical behavior of short single-stranded and partially and fully double-stranded DNA molecules attached via one end to a self-assembled monolayer on a gold surface. Our results confirm the previously proposed "mushroom-like" polymer structure for surface-attached, single-stranded DNA at low packing density and a "brush-like" structure for the same construct at higher density. At low density we observe a transition to "rigid rod" behavior upon addition of DNA complementary to the surface-attached single strand as the fraction of molecules that are double-stranded increases, with a concomitant increase in the SFA-observed thickness of the monolayer and the characteristic length of the observed repulsive forces. At higher densities, in contrast, this transition is effectively eliminated, presumably because the single-stranded state is already extended in its "brush" state. Taken together, these studies offer insights into the structure and physics of surface-attached short DNAs, providing new guidance for the rational design of DNA-modified functional surfaces.

Responses of bacterial communities and antibiotic resistance genes to nano-cellulose addition during pig manure composting.

Treatment with exogenous additives during composting can help to alleviate the accumulation of antibiotic resistance genes (ARGs) caused by the direct application of pig manure to farmland. In addition, nano-cellulose has an excellent capacity for adsorbing pollutants. Thus, the effects of adding 300, 600, and 900 mg/kg nano-cellulose to compost on the bacterial communities, mobile genetic elements (MGEs), and ARGs were determined in this study. After composting, treatment with nano-cellulose significantly reduced the relative abundance of ARGs, which was lowest in the compost product with 600 mg/kg added nano-cellulose. Nano-cellulose inhibited the rebound in ARGs from the cooling period to the maturity period, and weakened the selective pressure of heavy metals on microorganisms by passivating bio-Cu. The results also showed that MGEs explained most of the changes in the abundances of ARGs, and MGEs had direct effects on ARGs. The addition of 600 mg/kg nano-cellulose reduced the abundances of bacterial genera associated with ermQ, tetG, and other genes, and the number of links (16) between ARGs and MGEs was lowest in the treatment with 600 mg/kg added nano-cellulose. Therefore, adding 600 mg/kg nano-cellulose reduced the abundances of ARGs by affecting host bacteria and MGEs. The results obtained in this study demonstrate the positive effect of nano-cellulose on ARG pollution in poultry manure, where adding 600 mg/kg nano-cellulose was most effective at reducing the abundances of ARGs.

Structure and dynamics of lipid membranes interacting with antivirulence end-phosphorylated polyethylene glycol block copolymers.

The structure and dynamics of lipid membranes in the presence of extracellular macromolecules are critical for cell membrane functions and many pharmaceutical applications. The pathogen virulence-suppressing end-phosphorylated polyethylene glycol (PEG) triblock copolymer (Pi-ABAPEG) markedly changes the interactions with lipid vesicle membranes and prevents PEG-induced vesicle phase separation in contrast to the unphosphorylated copolymer (ABAPEG). Pi-ABAPEG weakly absorbs on the surface of lipid vesicle membranes and slightly changes the structure of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) unilamellar vesicles at 37 °C, as evidenced by small angle neutron scattering. X-ray reflectivity measurements confirm the weak adsorption of Pi-ABAPEG on DMPC monolayer, resulting in a more compact DMPC monolayer structure. Neutron spin-echo results show that the adsorption of Pi-ABAPEG on DMPC vesicle membranes increases the membrane bending modulus κ.

Zwitterionic Polymer-Grafted Superhydrophilic and Superoleophobic Silk Fabrics for Anti-Oil Applications.

A highly anti-oil fabric membrane is synthesized by surface grafting of zwitterionic poly(sulfobetaine methacrylate) (PSBMA) onto the fabric surface. The fabric membrane is first enzymatically modified to create more reactive amine groups on the surface. A surface-initiated atom transfer radical polymerization (SI-ATRP) reaction is then performed to modify the fabric membrane surface with a dense PSBMA brush layer. Surface characterization indicates that the brush-grafted fabric membrane exhibits increased surface roughness and improved superhydrophilicity. The PSBMA-modified silk fabrics show a very large contact angle for oil droplets in water, and have excellent oil resistance in air and in water-oil mixtures.

[Material basis and mechanism of Xiao'er Resuqing Oral Liquid on hand, foot and mouth disease based on network pharmacology and molecular docking].

This paper aimed to investigate the active components and molecular mechanism of Xiao'er Resuqing Oral Liquid on hand, foot and mouth disease(HFMD) based on network pharmacology and molecular docking methods. The potential active components of 8 herbs in Xiao'er Resuqing Oral Liquid were selected through Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), Batman database and relevant literature consultation. Then related targets for the medicine were analyzed through PubChem and Swiss Target Prediction database, while related targets for HFMD were analyzed through GeneCards platform. The common targets for medicine and disease were put into STRING database to obtain the potential targets of Xiao'er Resuqing Oral Liquid for treatment of HFMD. The Cytoscape software was used to establish the "herbs-components-targets-disease" network. The protein-protein interaction(PPI) network was constructed based on STRING platform and Cytoscape software to screen the core targets. Based on Metascape platform, GO function enrichment analysis and KEGG signal pathway enrichment analysis were carried out. The main active components and potential key targets of Xiao'er Resuqing Oral Liquid were verified by molecular docking with Autodock vina 1.1.2 software. A total of 118 potential active components and 123 potential targets for treatment of HFMD were collected. PPI network indicated a total of 23 key targets, such as AKT1, MAPK1, IL6, VEGFA, EGFR, TNF, HRAS, CCND1, and CXCL8. GO function enrichment analysis results showed that there were 381 GO biological processes, 127 GO cellular components, and 117 GO molecular functions(P<0.01). KEGG enrichment analysis showed that 116 signal pathways were obtained(P<0.01), and the results showed that it was mainly associated with TNF signal pathway, IL-17 signal pathway, inflammatory mediator regulation of TRP channels, and cytokine-cytokine receptor interaction. Molecular docking results showed that the main active components all had a high binding ability with the main potential key targets. This study preliminarily investigated the multi-pathways, multi-targets and multi-components molecular mechanism of Xiao'er Resuqing Oral Liquid for treatment of HFMD, providing theoretical references for further researches on its active components and action mechanism.

Self-assembled nanoparticles of reduction-sensitive poly (lactic-co-glycolic acid)-conjugated chondroitin sulfate A for doxorubicin delivery: preparation, characterization and evaluation.

In this study, reduction-sensitive self-assembled polymer nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and chondroitin sulfate A (CSA) were developed and characterized. PLGA was conjugated with CSA via a disulfide linkage (PLGA-ss-CSA). The critical micelle concentration (CMC) of PLGA-ss-CSA conjugate is 3.5 µg/mL. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the nanoparticles (PLGA-ss-CSA/DOX) with high loading efficiency of 15.1%. The cumulative release of DOX from reduction-sensitive nanoparticles was only 34.8% over 96 h in phosphate buffered saline (PBS, pH 7.4). However, in the presence of 20 mM glutathione-containing PBS environment, DOX release was notably accelerated and almost complete from the reduction-sensitive nanoparticles up to 96 h. Moreover, efficient intracellular DOX release of PLGA-ss-CSA/DOX nanoparticles was confirmed by CLSM assay in A549 cells. In vitro cytotoxicity study showed that the half inhibitory concentrations of PLGA-ss-CSA/DOX nanoparticles and free DOX against A549 cells were 1.141 and 1.825 µg/mL, respectively. Therefore, PLGA-ss-CSA/DOX nanoparticles enhanced the cytotoxicity of DOX in vitro. These results suggested that PLGA-ss-CSA nanoparticles could be a promising carrier for drug delivery.

Rice No Pollen 1 (NP1) is required for anther cuticle formation and pollen exine patterning.

Angiosperm male reproductive organs (anthers and pollen grains) have complex and interesting morphological features, but mechanisms that underlie their patterning are poorly understood. Here we report the isolation and characterization of a male sterile mutant of No Pollen 1 (NP1) in rice (Oryza sativa). The np1-4 mutant exhibited smaller anthers with a smooth cuticle surface, abnormal Ubisch bodies, and aborted pollen grains covered with irregular exine. Wild-type exine has two continuous layers; but np1-4 exine showed a discontinuous structure with large granules of varying size. Chemical analysis revealed reduction in most of the cutin monomers in np1-4 anthers, and less cuticular wax. Map-based cloning suggested that NP1 encodes a putative glucose-methanol-choline oxidoreductase; and expression analyses found NP1 preferentially expressed in the tapetal layer from stage 8 to stage 10 of anther development. Additionally, the expression of several genes involved in biosynthesis and in the transport of lipid monomers of sporopollenin and cutin was decreased in np1-4 mutant anthers. Taken together, these observations suggest that NP1 is required for anther cuticle formation, and for patterning of Ubisch bodies and the exine. We propose that products of NP1 are likely important metabolites in the development of Ubisch bodies and pollen exine, necessary for polymerization, assembly, or both.

Liposomal paclitaxel versus docetaxel in induction chemotherapy using Taxanes, cisplatin and 5-fluorouracil for locally advanced nasopharyngeal carcinoma.

BACKGROUND: We wished to evaluate the efficacy and safety of liposomal paclitaxel and docetaxel for induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC). METHODS: A total of 1498 patients with newly-diagnosed NPC between 2009 and 2017 treated with IC plus concurrent chemotherapy were included in our observational study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and grade-3-4 toxicities were compared between groups using propensity score matching (PSM). RESULTS: In total, 767 patients were eligible for this study, with 104 (13.6%) and 663 (86.4%) receiving a liposomal paclitaxel-based and docetaxel-based taxanes, cisplatin and 5-fluorouracil (TPF) regimen, respectively. PSM identified 103 patients in the liposomal-paclitaxel group and 287 patients in the docetaxel group. There was no significant difference at 3 years for OS (92.2% vs. 93.9%, P = 0.942), PFS (82.6% vs. 81.7%, P = 0.394), LRFS (94.7% vs. 93.3%, P = 0.981) or DMFS (84.6% vs. 87.4%, P = 0.371) between the two groups after PSM. Significant interactions were not observed between the effect of chemotherapy regimen and sex, age, T stage, N stage, overall stage, or Epstein-Barr virus DNA level in the subgroup multivariate analysis. The prevalence of grade-3-4 leukopenia and neutropenia in the liposomal-paclitaxel group was significantly lower than that of the docetaxel group (P < 0.05 for all). CONCLUSIONS: Compared with docetaxel, liposomal paclitaxel has identical anti-tumor efficacy, but causes fewer and milder adverse reactions in IC for NPC.

Radiotherapy-Sensitized Tumor Photothermal Ablation Using γ-Polyglutamic Acid Nanogels Loaded with Polypyrrole.

Development of versatile nanoscale platforms for cancer diagnosis and therapy is of great importance for applications in translational medicine. In this work, we present the use of γ-polyglutamic acid (γ-PGA) nanogels (NGs) to load polypyrrole (PPy) for thermal/photoacoustic (PA) imaging and radiotherapy (RT)-sensitized tumor photothermal therapy (PTT). First, a double emulsion approach was used to prepare the cystamine dihydrochloride (Cys)-cross-linked γ-PGA NGs. Next, the cross-linked NGs served as a reactor to be filled with pyrrole monomers that were subjected to in situ oxidation polymerization in the existence of Fe(III) ions. The formed uniform PPy-loaded NGs having an average diameter of 38.9 ± 8.6 nm exhibited good water-dispersibility and colloid stability. The prominent near-infrared (NIR) absorbance feature due to the loaded PPy endowed the NGs with contrast enhancement in PA imaging. The hybrid NGs possessed excellent photothermal conversion efficiency (64.7%) and stability against laser irradiation, and could be adopted for PA imaging and PTT of cancerous cells and tumor xenografts. Importantly, we also explored the cooperative PTT and X-ray radiation-mediated RT for enhanced tumor therapy. We show that PTT of tumors can be more significantly sensitized by RT using the sequence of laser irradiation followed by X-ray radiation as compared to using the reverse sequence. Our study suggests a promising theranostic platform of hybrid NGs that may be potentially utilized for PA imaging and combination therapy of different types of tumors.

Physical Stability of Amorphous Solid Dispersions: a Physicochemical Perspective with Thermodynamic, Kinetic and Environmental Aspects.

PURPOSE: Amorphous solid dispersions (ASDs) have been widely used in the pharmaceutical industry for solubility enhancementof poorly water-soluble drugs. The physical stability, however, remainsone of the most challenging issues for the formulation development.Many factors can affect the physical stability via different mechanisms, and therefore an in-depth understanding on these factors isrequired. METHODS: In this review, we intend to summarize the physical stability of ASDsfrom a physicochemical perspective whereby factors that can influence the physical stability areclassified into thermodynamic, kinetic and environmental aspects. RESULTS: The drug-polymer miscibility and solubility are consideredas the main thermodynamicfactors which may determine the spontaneity of the occurrence of the physical instabilityof ASDs. Glass-transition temperature,molecular mobility, manufacturing process,physical stabilityof amorphous drugs, and drug-polymerinteractionsareconsideredas the kinetic factors which areassociated with the kinetic stability of ASDs on aging. Storage conditions including temperature and humidity could significantly affect the thermodynamicand kineticstabilityof ASDs. CONCLUSION: When designing amorphous solid dispersions, it isrecommended that these thermodynamic, kinetic and environmental aspects should be completely investigatedand compared to establish rationale formulations for amorphous solid dispersions with high physical stability.