Advances in liposomes loaded with photoresponse materials for cancer therapy.

Cancer treatment is presently a significant challenge in the medical domain, wherein the primary modalities of intervention include chemotherapy, radiation therapy and surgery. However, these therapeutic modalities carry side effects. Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as promising modalities for the treatment of tumors in recent years. Phototherapy is a therapeutic approach that involves the exposure of materials to specific wavelengths of light, which can subsequently be converted into either heat or Reactive Oxygen Species (ROS) to effectively eradicate cancer cells. Due to the hydrophobicity and lack of targeting of many photoresponsive materials, the use of nano-carriers for their transportation has been extensively explored. Among these nanocarriers, liposomes have been identified as an effective drug delivery system due to their controllability and availability in the biomedical field. By binding photoresponsive materials to liposomes, it is possible to reduce the cytotoxicity of the material and regulate drug release and accumulation at the tumor site. This article provides a comprehensive review of the progress made in cancer therapy using photoresponsive materials loaded onto liposomes. Additionally, the article discusses the potential synergistic treatment through the combination of phototherapy with chemo/immuno/gene therapy using liposomes.

Multi-target meridians classification based on the topological structure of anti-cancer phytochemicals using deep learning.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) meridian is the key theoretical guidance of prescription against tumor in clinical practice. However, there is no scientific and systematic verification of therapeutic action of herbs under meridians context. Several studies have determined the Chinese herbal medicine (CHM) phytochemicals for intrinsic attribute or meridians classification based on artificial intelligence (AI) tools. However, it is challenging to represent the complex molecular structures with large heterogeneity through the current technologies. In addition, the multiple correspondence between herbs and meridians has not been paid much attention. AIM OF THE STUDY: We aim to develop an AI framework to classify multi-target meridians through the topological structure of phytochemicals. MATERIALS AND METHODS: A total of 354 anti-cancer herbs, their corresponding TCM meridians and 5471 ingredient compounds were collected from public databases of CancerHSP, ETCM, and Hit 2.0. The statistical analysis of herbal and compound datasets, clustering analysis of the associated cancers, and correlational analysis of meridian tropism were preliminary conducted. Then a deep learning (DL) hybrid model named GRMC consisting of graph convolutional network (GCN) and recurrent neural network (RNN) was employed to generate the meridian multi-label sequences based on molecular graph. RESULTS: The curing herbs against tumors have tight relationships to lung, liver, stomach, and spleen meridians. These herbs behave different properties in curing certain cancer. Certain cancer types have co-occurrence such as ovarian, bladder and cervical cancer. Compounds have multitarget meridians with characteristics of higher-order correlations. Compared with the other state-of-the-art algorithms on the datasets and previous methods dealing with conventional fixed fingerprints of herbal compounds, the proposed GRMC has superior overall performance on testing dataset with the one error of 0.183, hamming loss of 0.112, mean averaged accuracy (MAA) of 0.855, mean averaged precision (MAP) of 0.891, mean averaged recall (MAR) of 0.812, and mean averaged F1 score (MAF) of 0.849. CONCLUSIONS: The proposed method can predict multi-targeted meridians through neural graph features in herbal compounds and outperforms several comparison methods. It could provide a basis for understanding the molecular scientific evidence of TCM meridians.

Digestion and utilization of plant-based diets by transgenic pigs secreting ß-glucanase, xylanase, and phytase in their salivary glands.

Novel transgenic (TG) pigs co-expressing three microbial enzymes, ß-glucanase, xylanase, and phytase, in their salivary glands were previously generated, which exhibited reduced phosphorus and nitrogen emissions and improved growth performances. In the present study, we attempted to explore the age-related change of the TG enzymic activity, the residual activity of the enzymes in the simulated gastrointestinal tract, and the effect of the transgenes on the digestion of nitrogen and phosphorus content in the fiber-rich, plant-based diets. Results showed that all the three enzymes were stably expressed over the growing and finishing periods in the F2 generation TG pigs. In simulated gastric juice, all the three enzymes exhibited excellent gastrointestinal environment adaptability. The apparent total tract digestibility of phosphorus was increased by 69.05% and 499.64%, while fecal phosphate outputs were decreased by 56.66% and 37.32%, in the TG pigs compared with the wild-type littermates fed with low non-starch polysaccharides diets and high fiber diets, respectively. Over half of available phosphorus and water-soluble phosphorus in fecal phosphorus were reduced. We also found the performance of phosphorus, calcium, and nitrogen retention rates were significantly improved, resulting in faster growth performance in TG pigs. The results indicate that TG pigs can effectively digest the high-fiber diets and exhibit good growth performance compared with wild type pigs.

A comparison of the growth status, rainfall retention and purification effects of four green roof plant species.

Vegetation is a key component of green roofs and one of the most important factors affecting the rainfall quantity and quality of green roofs. Four plant species (Sedum lineare Thunb., Sedum spurium 'Coccineum', Sedum aizoon L. and Sedum spectabile) and two planting methods (single-plant and mixed-plant) were tested on extensive green roofs (EGRs) in 2019. Plant growth status (plant height and vegetation coverage), rainfall volume control, nutrient concentration and load reduction were used to analyse the impact of the situation and the different plant growth conditions. The results showed that the growth status of Sedum lineare Thunb., Sedum aizoon L. and Sedum spectabile was great, and the vegetation coverage was more than 95% in summer. Each EGR with different sedum species had strong rainfall retention effects. The average retention rates of Sedum spectabile, Sedum lineare Thunb, mixed plants, Sedum aizoon L. and Sedum spurium 'Coccineum' were 90.98% and 91.38%, 88.51%, 83.42% and 84.17%, respectively. The average total nitrogen (TN) and nitrate nitrogen (NO3--N) concentrations of Sedum lineare Thunb. were 13.77 mg/L and 7.64 mg/L, which were higher than those of other sedum species, and the average concentrations of ammonia nitrogen (NH4+-N) and total phosphorus (TP) of mixed plants were 4.01 mg/L and 0.48 mg/L, which were higher than those of single plants. Different plant species had different effects on nutrient loads. The EGRs of single plants and mixed plants indicated sinks of TN and NH4-N and sources of TP, but the performance of NO3--N was inconsistent. Comprehensively, Sedum lineare Thunb., Sedum aizoon L. and Sedum spectabile were suitable for the green roofs. This study provides scientific support for the green roofs' application of actual projects and has a strong reference value for the development of green infrastructure.

The improved targeting of an aspirin prodrug albumin-based nanosystem for visualizing and inhibiting lung metastasis of breast cancer.

Lung metastasis is the principal reason for the majority of deaths from breast cancer. The nonsteroidal anti-inflammatory drug aspirin can prevent lung metastasis in breast tumors via inhibiting heparanase. However, the lack of specific targets and limited accumulation at the site of the tumor have thus far hindered the use of aspirin in oncotherapy. In this study, we developed the nanoplatform FA-BSA@DA and loaded it with the versatile aspirin prodrug DA to visualize and inhibit breast cancer metastasis via targeting heparanase. This nanosystem can be effectively targeted to folic acid (FA)-positive tumor cells, and would then subsequently release a high dose of DA, whose ester bond is specifically ruptured by H2O2 in the tumor microenvironment to afford the therapeutic drug aspirin and near-infrared (NIR) fluorescent reporter DCM. The released aspirin can effectively prevent breast cancer lung metastasis through the inhibition of heparanase activity, and the NIR fluorescent signals emitted from DCM can be used to monitor and evaluate the metastasis levels of breast cancer. Our results showed that the expression of heparanase was significantly decreased, and lung metastasis from breast cancer was effectively monitored and inhibited after treatment with FA-BSA@DA. Furthermore, the collaborative therapy nanoplatform FA-BSA@DA/DOX exhibited strong therapeutic effects in the treatment of breast cancer in vitro and in vivo via the introduction of doxorubicin (DOX) to the system, which resulted in an even stronger result due to its synergistic effects with aspirin. This heparanase-reliant strategy has profound significance for the extended development of nanoplatforms based on versatile aspirin prodrugs, which may offer a solution to clinically prevent breast cancer recurrence and lung metastasis.

Upregulation of transcription factor 4 downregulates NaV1.8 expression in DRG neurons and prevents the development of rat inflammatory and neuropathic hypersensitivity.

The voltage sodium channel 1.8 (NaV1.8) in the dorsal root ganglion (DRG) neurons contributes to the initiation and development of chronic inflammatory and neuropathic pain. However, an effective intervention on NaV1.8 remains to be studied in pre-clinical research and clinical trials. In this study, we aimed to investigate whether transcription factor 4 (TCF4) overexpression represses NaV1.8 expression in DRG neurons, thus preventing the development of chronic pain. Using chromatin immunoprecipitation (CHIP), we verified the interaction of TCF4 and sodium voltage-gated channel alpha subunit 10A (SCN10A) enhancer in HEK293 cells and rat DRG neurons. Using a dual luciferase reporter assay, we confirmed the transcriptional inhibition of TCF4 on SCN10A promoter in vitro. To investigate the regulation of TCF4 on Nav1.8, we then upregulated TCF4 expression by intrathecally delivering an overexpression of recombinant adeno-associated virus (rAAV) in the Complete Freund's adjuvant (CFA)-induced inflammatory pain model and spared nerve injury (SNI)-induced neuropathic pain model. By using a quantitative polymerase chain reaction (qPCR), western blot, and immunostaining, we evaluated NaV1.8 expression after a noxious stimulation and the application of the TCF4 overexpression virus. We showed that the intrathecal delivery of TCF4 overexpression virus significantly repressed the increase of NaV1.8 and prevented the development of hyperalgesia in rats. Moreover, we confirmed the efficient role of an overexpressed TCF4 in preventing the CFA- and SNI-induced neuronal hyperexcitability by calcium imaging. Our results suggest that attenuating the dysregulation of NaV1.8 by targeting TCF4 may be a novel therapeutic strategy for chronic inflammatory and neuropathic pain.

Novel transgenic pigs with enhanced growth and reduced environmental impact.

In pig production, inefficient feed digestion causes excessive nutrients such as phosphorus and nitrogen to be released to the environment. To address the issue of environmental emissions, we established transgenic pigs harboring a single-copy quad-cistronic transgene and simultaneously expressing three microbial enzymes, ß-glucanase, xylanase, and phytase in the salivary glands. All the transgenic enzymes were successfully expressed, and the digestion of non-starch polysaccharides (NSPs) and phytate in the feedstuff was enhanced. Fecal nitrogen and phosphorus outputs in the transgenic pigs were reduced by 23.2-45.8%, and growth rate improved by 23.0% (gilts) and 24.4% (boars) compared with that of age-matched wild-type littermates under the same dietary treatment. The transgenic pigs showed an 11.5-14.5% improvement in feed conversion rate compared with the wild-type pigs. These findings indicate that the transgenic pigs are promising resources for improving feed efficiency and reducing environmental impact.

The metabolomic study on atherosclerosis mice and its application in a traditional Chinese medicine Sishen granule.

Although an atherosclerosis (AS) model using low-density lipoprotein receptor deletion mice has been widely applied, its pathological pathway in metabolite level is still not clear. To further reveal the metabolite profile and identify the potential biomarkers in AS development, a serum metabolomic approach was developed based on reversed-phase liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). The established metabolomic platform was also used for elucidating the therapeutic mechanism of a traditional Chinese medicine named Sishen granule (SSKL). Twenty-one potential biomarkers in AS mouse serum were identified. Through functional analysis of these biomarkers, inflammation, proliferation, dysfunction of energy metabolism and amino acid metabolism were considered the most relevant pathological changes in AS. DNA damage products were found for the first time in the metabolomic study of AS. The network established by 20 biomarkers revealed that pyruvate metabolism, citrate cycle, fatty acid metabolism and urea metabolism were seriously disturbed. This metabolomic study not only supplied a systematic view of the progression of AS but also provided a theoretical basis for the treatment of AS. This metabolomic study also demonstrated that SSKL had therapeutic effectiveness for AS through partly reversing the inflammation reaction and amino acid metabolism dysfunction. Copyright © 2015 John Wiley & Sons, Ltd.

Metabolomic study on the faecal extracts of atherosclerosis mice and its application in a Traditional Chinese Medicine.

The intestinal microbiota and their metabolites are closely related to the formation of atherosclerosis (AS). In this study, a metabolomic approach based on the reversed-phase liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) platform was established to analyze the metabolic profiling of fecal extracts from AS mice model. The established metabolomic platform was also used for clearing the effective mechanism of a Traditional Chinese Medicine (TCM) named Sishen granule (SSKL). Totally, sixteen potential biomarkers in faeces of AS mice were identified and 5 of them could be reversed by SSKL. Through functional analysis of these biomarkers and the established network, lipid metabolism, cholesterol metabolism, energy cycle, and inflammation reaction were considered as the most relevant pathological changes in gastrointestinal tract of AS mice. The metabolomic study not only revealed the potential biomarkers in AS mice' faeces but also supplied a systematic view of the pathological changes in gastrointestinal metabolite in AS mice. This metabolomic study also demonstrated that SSKL had the therapeutic effectiveness on AS through partly reversing the lipid metabolism, inflammation and energy metabolism.

Impact of suspended inorganic particles on phosphorus cycling in the Yellow River (China).

Phosphorus (P) in water and sediment in the Yellow River was measured for 21 stations from the source to the Bohai Sea in 2006-2007. The average total particulate matter (TPM) increased from 40 mg/L (upper reaches) to 520 mg/L (middle reaches) and 950 mg/L in the lower reaches of the river. The average dissolved PO4 concentration (0.43 µmol/L) was significantly higher than that in 1980's but lower than the world average level despite high nutrient input to the system. Much of the P input was removed by adsorption, which was due to the high TPM rather than the surface activity of the particles since they had low labile Fe and low affinity for P. The sediment was a sink for P in the middle to lower reaches but not in the upper to middle reaches. TPM has been reduced by more than an order of magnitude due to artificial dams operating over recent decades. Modeling revealed that TPM of 0.2-1 g/L was a critical threshold for the Yellow River, below which most of the phosphate input cannot be removed by the particles and may cause eutrophication. These findings are important for river management and land-ocean modeling of global biogeochemical P cycling.

[Characteristics of phosphorus sorption on Yellow River sediments from Inner Mongolia reach].

Sorption behavior of phosphorus on sediment samples taken from Inner Mongolia reach of the Yellow River in 6 different geographical sites was determined in laboratory, and the correlation between chemical-physical properties of the sediments and their phosphorus sorption characteristics was analyzed. The maximum sorption capacities were 43.64-85.46 mg/kg. The zero equilibrium P concentration (EPC0) of the sediments ranged from 0.0003 to 0.0198 mg/L, which was positively correlated to the contents of native adsorbed P (NAP). The sediments played a dual role of sink and source of P at different geographical sites. Sediments from Shizuishan, Wulateqianqi and Qingshuihe along the Yellow River were sources of phosphorus, while sediments from Wuhai, Linhe and Baotou cross sections were sinks of phosphorus, at the typical P concentrations of the river water. However, both the sorption and desorption capacities were low at the conditions tested here. The Langmuir sorption constant (k) was positively correlated to the cation exchange capacity (CEC), organic matter and clay mineral content, but negatively correlated to the particle size of the sediments. The maximum sorption capacity of phosphorus was remarkably correlated to the active Fe content. Active Fe played a key role in holding phosphorus on the sediments.

[Effects of perioperative music on sedation in patients undergoing gynecological surgery under intravertebral anesthesia].

OBJECTIVE: To investigate the effects of music on propofol target-controlled infusion (TCI) in patients during gynecological surgery under intravertebral anesthesia. METHODS: One hundred and ten patients scheduled for gynecological surgery under intravertebral anesthesia were randomly assigned to two groups. The music group patients were asked to determine music and its sound volume preoperatively, which were played from 6 min before the surgery to the end. A loading dose of 1 microg/kg fentanyl and 0.5 mg/kg propofol was administered intravenously to all the patients 5 min prior to operation. At the beginning of surgery, the TCI of propofol was initiated at propofol target controlled concentration of 2 microg/ml, which was modulated at a grade of 0.2 microg/ml every 10 min to maintain an observer's assessment of alertness/sedation (OAA/S) score of 3 intraoperatively. Induction time of sedation, intraoperative amount of propofol and patient's satisfaction of sedation were assessed. RESULTS: (1) The music group patients had a significant shorter induction time of sedation (12 min +/- 12 min) than the controls (18 min +/- 12 min) (P < 0.01). (2) The music group patients had a significant less propofol target-controlled concentration (1.6 microg/ml +/- 0.3 microg/ml) and delivers (171 mg +/- 98 mg) than the controls (2.4 microg/ml +/- 0.4 microg/ml and 251 mg +/- 92 mg) (both P < 0.01). (3) The music group patients had a significant higher satisfaction (9.7 +/- 0.6) than the controls (8.1 +/- 1.0) (P < 0.01). CONCLUSION: Music has perfect sedative effects in patients undergoing gynecological surgery under intravertebral anesthesia.