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Drought has broad and deep influences on ecosystem dynamics and functions, particularly considering the lagged and cumulative effects of drought. Yet the individual role of climate variables in mediating such drought effects on vegetation remains largely unknown. Based on the Normalized Difference Vegetation Index (NDVI) and the standard precipitation evapotranspiration index (SPEI), here, we investigated the patterns and mechanisms of drought effects on alpine grasslands in the Qinghai–Tibetan Plateau (QTP) from 1982 to 2015. Drought imposed widespread lagged and cumulative impacts on alpine grasslands with notable spatial heterogeneity, showing that the southwestern and northeastern parts of the plateau were more sensitive and responded quickly to drought. Further, drought effects showed an evident elevation dependence across different grassland types, which could be explained by altitudinal shifts in climatic factors, including temperature and precipitation. Precipitation was the dominant factor in drought effects on alpine meadows, while temperature dominated the drought impacts on the alpine steppes. Such a divergent dominant factor implied that there would be different vegetation responses to future climate change among diverse types of alpine grasslands. To maintain the sustainability of alpine grassland, more effort should be applied to alpine steppes regarding pasture management, particularly in response to extreme drought due to warmer climates in the future. [ABSTRACT FROM AUTHOR]

Understanding the roles of core bacterial taxa in forage production is crucial for developing sustainable fertilization practices that enhance the soil bacteria and forage yield. This study aims to investigate the impact of different fertilization regimes on soil bacterial community structure and function, with a particular focus on the role of core bacterial taxa in contributing to soil nutrient content and enhancing forage yield. Field experiments and high-throughput sequencing techniques were used to analyze the soil bacterial community structure and function under various fertilization regimes, including six treatments, control with no amendment (CK), double the standard rate of organic manure (T01), the standard rate of organic manure with nitrogen input equal to T04 (T02), half the standard rate of inorganic fertilizer plus half the standard rate of organic manure (T03), the standard rate of inorganic fertilizer reflecting local practice (T04), and double the standard rate of inorganic fertilizer (T05). The results demonstrated that organic manure treatments, particularly T01, significantly increased the forage yield and the diversity of core bacterial taxa. Core taxa from the Actinomycetota, Alphaproteobacteria, and Gammaproteobacteria classes were crucial in enhancing the soil nutrient content, directly correlating with forage yield. Fertilization significantly influenced functions relating to carbon and nitrogen cycling, with core taxa playing central roles. The diversity of core microbiota and soil nutrient levels were key determinants of forage yield variations across treatments. These findings underscore the critical role of core bacterial taxa in agroecosystem productivity and advocate for their consideration in fertilization strategies to optimize forage yield, supporting the shift towards sustainable agricultural practices. [ABSTRACT FROM AUTHOR]

With global climate change leading to increasing intensity and frequency of droughts, as well as the growing problem of soil salinization, these factors significantly affect crop growth, yield, and resilience to adversity. Oats are a cereal widely grown in temperate regions and are rich in nutritive value; however, the scientific literature on the response of oat to drought and salt stress has not yet been analyzed in detail. This study comprehensively analyzed the response of oat to drought stress and salt stress using data from the Web of Science core database and bibliometric methods with R (version4.3.1), VOSviewer (version 1.6.19), and Citespace (version6.3.1.0) software. The number of publications shows an increasing trend in drought stress and salt stress in oat over the past 30 years. In the field of drought-stress research, China, the United States, and Canada lead in terms of literature publication, with the most academic achievements being from China Agricultural University and Canadian Agricultural Food University. The journal with the highest number of published papers is Field Crops Research. Oat research primarily focuses on growth, yield, physiological and biochemical responses, and strategies for improving drought resistance. Screening of drought-tolerant genotypes and transformation of drought-tolerant genes may be key directions for future oat drought research. In the field of salt-stress research, contributions from China, the United States, and India stand out, with the Chinese Academy of Agricultural Sciences and Inner Mongolia Agricultural University producing the most significant research results. The largest number of published articles has been found in the Physiologia Plantarum journal. Current oat salt-stress research primarily covers growth, physiological and biochemical responses, and salt-tolerance mechanisms. It is expected that future oat salt research will focus more on physiological and biochemical responses, as well as gene-editing techniques. Despite achievements under single-stress conditions, combined drought and salt-stress effects on oat remain understudied, necessitating future research on their interaction at various biological levels. The purpose of this study is to provide potential theoretical directions for oat research on drought and salt stress. [ABSTRACT FROM AUTHOR]

Burrowing animals are a critical driver of terrestrial ecosystem functioning, but we know little about their effects on soil microbiomes. Here, we evaluated the effect of burrowing animals on microbial assembly processes and co-occurrence patterns using soil microbiota from a group of habitats disturbed by Plateau pikas (Ochtona curzoniae). Pika disturbance had different impacts on bacterial and fungal communities. Fungal diversity generally increased with patch area, whereas bacterial diversity decreased. These strikingly different species–area relationships were closely associated with their community assembly mechanisms. The loss of bacterial diversity on larger patches was largely driven by deterministic processes, mainly due to the decline of nutrient supply (e.g., organic C, inorganic N). In contrast, fungal distribution was driven primarily by stochastic processes that dispersal limitation contributed to their higher fungal diversity on lager patches. A bacterial co-occurrence network exhibited a positive relationship of nodes and linkage numbers with patch area, and the fungal network presented a positive modularity–area relationship, suggesting that bacteria tended to form a closer association community under pika disturbance, while fungi tended to construct a higher modularity network. Our results suggest that pikas affects the microbial assembly process and co-occurrence patterns in alpine environments, thereby enhancing the current understanding of microbial biogeography under natural disturbances. [ABSTRACT FROM AUTHOR]

Drought and poor soil quality are the main characteristics of extreme environments in arctic–alpine areas. Understanding how herbaceous plants in alpine grasslands maintain the normal supply and utilisation of nutrients under different rainfall conditions is key to maintaining population stability. In the present study, the native plants Poa crymophila and Stipa purpurea of the Qinghai–Tibet Plateau were used to conduct a controlled experiment involving water and fertiliser to analyse their physiological responses in terms of nutrient uptake and utilisation. The results showed that decreased soil moisture increased proline and non-structural carbohydrates in P. crymophila, mainly accumulating in the leaves and stems. Nitrogen (N) addition promoted proline accumulation, whereas nonstructural carbohydrate content decreased. However, the proline and non-structural carbohydrate contents of S. purpurea were less affected by water and fertiliser. Additionally, drought restricted rhizospheric and non-rhizospheric alkaline-hydrolysed N release, increased rapidly available phosphorus (RAP) content in rhizospheric soil, limited root growth, and reduced surface area, root length, and root volume. Both aboveground and underground N fertiliser utilisation rates decreased. Under well-hydrated conditions (WH), high N levels increased rhizospheric alkaline-hydrolysed N and urease activity while inhibiting RAP and activity of alkaline phosphatase contents, thereby limiting root growth and reducing N fertiliser utilisation. The results indicate that both plant species have relatively low overall nutrient requirements that are limited mainly by water availability. The addition of low amounts of fertiliser is beneficial for nutrient release and utilisation, improving their adaptability to arctic–alpine environments and their suitability and superiority in the community. This study has significant implications for nutrient management and ecological restoration measures in arctic–alpine grasslands. [ABSTRACT FROM AUTHOR]

Ochratoxins are the secondary metabolites of Penicillium and Aspergillus, among which ochratoxin A (OTA) is the most toxic molecule. OTA is widely found in food and agricultural products. Due to its severe nephrotoxicity, immunotoxicity, neurotoxicity, and teratogenic mutagenesis, it is essential to develop effective, economical, and environmentally friendly methods for OTA decontamination and detoxification. This review mainly summarizes the application of technology in OTA prevention, removal, and detoxification from physical, chemical, and biological aspects, depending on the properties of OTA, and describes the advantages and disadvantages of each method from an objective perspective. Overall, biological methods have the greatest potential to degrade OTA. This review provides some ideas for searching for new strains and degrading enzymes. [ABSTRACT FROM AUTHOR]

Drought and nutrient deficiency pose great challenges to the successful establishment of native plants on the Qinghai-Tibet Plateau. The dominant factors and strategies that affect the adaptation of alpine herbs to dry and nutrient-deficient environments remain unclear. Three water gradients were established using two-factor controlled experiments: low water (WL), medium water (WM), and high water (WH). The field water-holding capacities were 35%, 55%, and 75%, respectively. Nitrogen fertilizer (N) was applied at four levels: control (CK), low (FL), medium (FM), and high (FH) at 0, 110, 330, and 540 mg/kg, respectively. The results revealed that N was the main limiting factor, rather than phosphorous (P), in Festuca coelestis under drought stress. Under water shortage conditions, F. coelestis accumulated more proline and non-structural carbohydrates, especially in the aboveground parts of the leaves and stems; however, the root diameter and aboveground nitrogen use efficiency were reduced. Appropriate N addition could mitigate the adverse effects by increasing the release of N, P, and enzyme activity in the bulk soil and rhizosphere to balance their ratio, and was mainly transferred to the aboveground parts, which optimized the supply uptake relationship. The effects of water and fertilizer on the physiological adaptability and nutrient utilization of F. coelestis were verified using structural equation modeling. Based on their different sensitivities to water and nitrogen, the WHFM treatment was more suitable for F. coelestis establishment. Our results demonstrated that the disproportionate nutrient supply ability and preferential supply aboveground compared to below ground were the main factors influencing F. coelestis seedling establishment under drought conditions. This study provides evidence for a better understanding of herbaceous plants living in high mountain regions and offers important information for reducing the risk of ecological restoration failure in similar alpine regions. [ABSTRACT FROM AUTHOR]

Neutral/negatively charged nanoparticles are beneficial to reduce plasma protein adsorption and prolong their blood circulation time, while positively charged nanoparticles easily transverse the blood vessel endothelium into a tumor and easily penetrate the depth of the tumor via transcytosis. Γ-Glutamyl transpeptidase (GGT) is overexpressed on the external surface of endothelial cells of tumor blood vessels and metabolically active tumor cells. Nanocarriers modified by molecules containing γ-glutamyl moieties (such as glutathione, G-SH) can maintain a neutral/negative charge in the blood, as well as can be easily hydrolyzed by the GGT enzymes to expose the cationic surface at the tumor site, thus achieving good tumor accumulation via charge reversal. In this study, DSPE-PEG2000-GSH (DPG) was synthesized and used as a stabilizer to generate paclitaxel (PTX) nanosuspensions for the treatment of Hela cervical cancer (GGT-positive). The obtained drug-delivery system (PTX-DPG nanoparticles) was 164.6 ± 3.1 nm in diameter with a zeta potential of −9.85 ± 1.03 mV and a high drug-loaded content of 41.45 ± 0.7%. PTX-DPG NPs maintained their negative surface charge in a low concentration of GGT enzyme (0.05 U/mL), whereas they showed a significant charge-reversal property in the high-concentration solution of GGT enzyme (10 U/mL). After intravenous administration, PTX-DPG NPs mainly accumulated more in the tumor than in the liver, achieved good tumor-targetability, and significantly improved anti-tumor efficacy (68.48% vs. 24.07%, tumor inhibition rate, p < 0.05 in contrast to free PTX). This kind of GGT-triggered charge-reversal nanoparticle is promising to be a novel anti-tumor agent for the effective treatment of such GGT-positive cancers as cervical cancer. [ABSTRACT FROM AUTHOR]

Mitochondria are involved in various stages of cancer cell diffusion and metastasis. Therefore, targeting tumor mitochondria with antineoplastic medicines to cause mitochondria to initiate apoptosis may be an effective strategy for cancer therapy. Here, in order to enhance the anti-tumor efficacy of the antineoplastic agent hydroxycamptothecin (HCPT), the mitochondrial targeting ligand 4-(carboxybutyl) triphenylphosphine bromide (TPP) was attached to HCPT by an ester linkage. The resultant TPP-HCPT (TH) conjugate could self-assemble into nano-aggregates, with a mean particle size of 203.2 nm and a polydispersity index (PDI) value of 0.312. The TH conjugate could also co-assembly with mPEG3000-PLGA5000 into nanoparticles (TH-NPs), with a mean diameter of 86.41 nm, a PDI value of 0.256 and a zeta potential of −0.125 mV. In contrast to HCPT injections, TH aggregates displayed enhanced cellular uptake, mitochondria-targetability and cytotoxicity against 4T1 cells, while TH-NPs showed even better improvement than TH aggregates. In the in vivo study, TH aggregates displayed higher anti-tumor efficacy in 4T1 tumor-bearing mice than HCPT injections (tumor inhibition rate, 55.71% vs. 69.17%), and TH-NPs displayed more superior anti-tumor effects (tumor inhibition rate, 80.02%). In conclusion, our research demonstrated that the TPP-HCPT conjugate and its nano-formulations, including TH aggregates and TH-NPs, may be a promising mitochondria-targeting anticancer medicine for cancer therapy. As far as we know, this is the first report in which TPP and HCPT have been conjugated directly for this aim. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of nanoscale drug delivery systems is related to particle size, zeta potential, morphology, and other physicochemical properties. The structure and composition of nanocarriers may affect their physicochemical properties. To systematically evaluate these characteristics, three analogues, namely polyethylene glycol (PEG), PEG-conjugated octadecylamine (PEG-C18), and tri(ethylene glycol) (TEG), were explored as nanocarriers to entrap celastrol (CSL) via the injection-combined dialysis method. CSL nanoparticles were successfully prepared as orange milky solutions, which revealed a similar particle size of approximately 120 nm, with narrow distribution and a negative zeta potential of −20 mV. All these CSL nanoparticles exhibited good storage stability and media stability but presented different drug-loading capacities (DLCs), release profiles, cytotoxicity, and hemolytic activity. For DLCs, PEG-C18/CSL exhibited better CSL entrapment capacity. Regarding the release profiles, TEG/CSL showed the lowest release rate, PEG-C18/CSL presented a moderate release rate, and PEG/CSL exhibited a relatively fast release rate. Based on the different release rates, PEG-C18/CSL and TEG/CSL showed higher degrees of cytotoxicity than PEG/CSL. Furthermore, TEG/CSL showed the lowest membrane toxicity, and its hemolytic rate was below 20%. These results suggest that the structural effects of nanocarriers can affect the interactions between nanocarriers and drugs, resulting in different release profiles and antitumor activity. [ABSTRACT FROM AUTHOR]

Oligoethylene glycol dendron (G2) has been used in drug delivery due to its unique dendritic structure and excellent properties. In order to investigate the effects of lipophilic chains on drug delivery, the amphiphilic hybrid compound G2-C18 is synthesized, and celastrol (CSL) is selected to prepare "core-shell" structured CSL-G2-C18 nanoparticles (NPs) via the antisolvent precipitation method. Meanwhile, CSL-G2 NPs are prepared as the control. The two NPs show similar particle sizes and polydispersity indexes, while their morphologies exhibit dramatic differences. CSL-G2 NPs are solid spherical particles, while G2-C18 NPs are vesicles. The two NPs present ideal stability and similar release tendencies. The in vitro toxicity results show that the cell inhibition effect of CSL-loaded NPs is significantly enhanced when compared with free CSL, and the antitumor effect of CSL-G2-C18 NPs is stronger than that of CSL-G2 NPs. The IC50 value of CSL-G2 NPs and CSL-G2-C18 NPs is enhanced about 2.8-fold and 5-fold when compared with free CSL, respectively. The above results show that lipophilic chain-linking dendritic hybrid nanocarriers promote antitumor activity by affecting the morphology of NPs, which may aid in the selection of carrier designs. [ABSTRACT FROM AUTHOR]

In order to improve the efficacy of doxorubicin in the treatment of breast cancer, we constructed a drug delivery system combined with local administration of Lycium barbarum polysaccharides (LBP) and photothermal-material polypyrrole nanoparticles (PPY NPs). In vitro cytotoxicity experiments showed that the inhibitory effect of DOX + LBP + PPY NPs on 4T1 cells under NIR (near infrared) laser was eight times that of DOX at the same concentration (64% vs. 8%). In vivo antitumor experiments showed that the tumor inhibition rate of LBP + DOX + PPY NPs + NIR reached 87.86%. The results of the H&E staining and biochemical assays showed that the systemic toxicity of LBP + DOX + PPY NPs + NIR group was reduced, and liver damage was significantly lower in the combined topical administration group (ALT 54 ± 14.44 vs. 28 ± 3.56; AST 158 ± 16.39 vs. 111 ± 20.85) (p < 0.05). The results of the Elisa assay showed that LBP + DOX + PPY NPs + NIR can enhance efficacy and reduce toxicity (IL-10, IFN-γ, TNF-α, IgA, ROS). In conclusion, LBP + DOX + PPY NPs combined with photothermal therapy can improve the therapeutic effect of DOX on breast cancer and reduce its toxic side effects. [ABSTRACT FROM AUTHOR]

Owing to its pH-sensitive property and chelating Cu2+ effect, poly(methacrylate citric acid) (PCA) can be utilized as a dual functional nanocarrier to construct a nanodelivery system. Negatively charged carboxyl groups can interact with positively charged antineoplastic drugs through electrostatic interaction to form stable drug nanoparticles (NPs). Through drug experimental screening, doxorubicin (DOX) was selected as the model drug, PCA/DOX NPs with a diameter of 84 nm were prepared, and the drug-loading content was 68.3%. PCA/DOX NPs maintained good stability and a sustained release profile. Cell experiments presented that PCA/DOX NPs could inhibit effectively the growth of 4T1 cells; the IC50 value was decreased by approximately 15-fold after incubation for 72 h. The cytotoxicity toward H9C2 was decreased significantly. Moreover, based on its ability to efficiently adsorb copper ions, PCA showed good vascular growth inhibition effect in vitro. Furthermore, animal experiments showed that PCA/DOX NPs presented stronger anticancer effects than DOX; the tumor inhibition rate was increased by 1.5-fold. Myocardial toxicity experiments also confirmed that PCA reduced the cardiotoxicity of DOX. In summary, PCA/DOX NPs show good antitumor efficacy and low toxicity, and have good potential for clinical application. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD), a nonpsychoactive major component derived from Cannabis sativa, widely used in neurodegenerative diseases, has now been proven to have growth inhibitory effects on many tumor cell lines, including breast tumors. Meanwhile CBD can effectively alleviate cancer-associated pain, anxiety, and depression, especially tumor cachexia, thus it is very promising as an anti-tumor drug with unique advantages. 20(S)-Protopanaxadiol (PPD) derived from the best-known tonic Chinese herbal medicine Ginseng was designed to be co-loaded with CBD into liposomes to examine their synergistic tumor-inhibitory effect. The CBD-PPD co-loading liposomes (CP-liposomes) presented a mean particle size of 138.8 nm. Further glycosyl-modified CP-liposomes (GMCP-liposomes) were prepared by the incorporation of n-Dodecyl β-D-maltoside (Mal) into the liposomal bilayer with glucose residue anchored on the surface to act as a ligand targeting the GLUT1 receptor highly expressed on tumor cells. In vivo studies on murine breast tumor (4T1 cells)-bearing BALB/c mice demonstrated good dose dependent anti-tumor efficacy of CP-liposomes. A high tumor inhibition rate (TIR) of 82.2% was achieved with good tolerance. However, glycosylation modification failed to significantly enhance TIR of CP-liposomes. In summary, combined therapy with PPD proved to be a promising strategy for CBD to be developed into a novel antitumor drug, with characteristics of effectiveness, good tolerance, and the potential to overcome tumor cachexia. [ABSTRACT FROM AUTHOR]

Naringenin (NRG) is a natural compound with several biological activities; however, its bioavailability is limited owing to poor aqueous solubility. In this study, NRG nanoparticles (NPs) were prepared using the wet media milling method. To obtain NRG NPs with a small particle size and high drug-loading content, the preparation conditions, including stirring time, temperature, stirring speed, and milling media amount, were optimized. The NRG (30 mg) and D-α-tocopherol polyethylene glycol succinate (10 mg) were wet-milled in deionized water (2 mL) with 10 g of zirconia beads via stirring at 50 °C for 2 h at a stirring speed of 300 rpm. As a result, the NRG NPs, with sheet-like morphology and a diameter of approximately 182.2 nm, were successfully prepared. The NRG NPs were stable in the gastrointestinal system and were released effectively after entering the blood circulation. In vivo experiments indicated that the NRG NPs have good antitussive effects. The cough inhibition rate after the administration of the NRG NPs was 66.7%, cough frequency was three times lower, and the potential period was 1.8 times longer than that in the blank model group. In addition, the enzyme biomarkers and histological analysis results revealed that the NRG NPs can effectively regulate the inflammatory and oxidative stress response. In conclusion, the NRG NPs exhibited good oral bioavailability and promoted antitussive and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Graphene oxide, as a new two-dimensional material, has a large specific surface area, high thermal stability, excellent mechanical stability and exhibits hydrophilic properties. By combining the carboxyl groups on the surface of graphene oxide with hydrophilic groups, surfactant-like polymers can be obtained. In this paper, based on the molecular dynamics method combined with the first nature principle, we first determine the magnitude of the binding energy of three different coupling agents—alkylamines, silane coupling agents, and haloalkanes—and analytically obtain the characteristics of the soft reaction. The high stability of alkylamines and graphene oxide modified by cetylamine, oil, and water models was also established. Then, three different chain lengths of simulated oil, modified graphene oxide–water solution, and oil-modified graphene oxide–water systems were established, and finally, the self-aggregation phenomenon and molecular morphology changes in modified graphene oxide at the oil–water interface were observed by an all-atom molecular dynamics model. The density profile, interfacial formation energy, diffusion coefficient and oil–water interfacial tension of modified graphene oxide molecules (NGOs) at three different temperatures of 300 K, 330 K, and 360 K were analyzed, as well as the relationship between the reduced interfacial tension and enhanced oil recovery (EOR). [ABSTRACT FROM AUTHOR]

Annona squamosa seed oil (ASSO), which is a waste product in the extraction of annonaceous acetogenins (ACGs), displays good antitumor activity against a variety of tumor cells. However, ASSO is insoluble and has low bioavailability. In order to improve the solubility and application value of ASSO, the seed oil nanoparticles (ASSO-NPs) were successfully prepared only using TPGS as a stabilizer. ASSO-NPs obtained were spherical with a uniform size (less than 200 nm). ASSO-NPs showed the good storage stability at 25 ± 2 °C and were suitable for both oral administration and intravenous injection. The antitumor study in vitro and in vivo demonstrated more enhanced antitumor efficacy of ASSO-NPs than free ASSO. The ASSO-NPs group (15 mg/kg) had the highest tumor inhibition rate (TIR) of 69.8%, greater than the ASSO solution (52.7%, 135 mg/kg, p < 0.05) in 4T1 tumor-bearing mice. The in vivo biodistribution data displayed that the fluorescence intensity of ASSO/DiR-NPs in tumor was similar to that in liver in the presence of the reticuloendothelial system. Besides, the relative tumor-targeting index (RTTI) of (ACGs + ASSO)-NPs was 1.47-fold that of ACGs delivered alone, and there is great potential in ASSO-NPs as tumor-targeted delivery vehicles. In this study, ASSO-NPs were firstly prepared by a very simple method with fewer excipients, which improved the solubility and antitumor activity of the ASSO, displaying a good prospect in the in vivo delivery of natural bioactive compounds. [ABSTRACT FROM AUTHOR]

Poly(amino acids) have advanced characteristics, including unique secondary structure, enzyme degradability, good biocompatibility, and stimuli responsibility, and are suitable as drug delivery nanocarriers for tumor therapy. The isoform structure of poly(amino acids) plays an important role in their antitumor efficacy and should be researched in detail. In this study, two kinds of pH-sensitive isoforms, including α-poly(glutamic acid) (α-PGA) and γ-PGA, were selected and used as nanocarriers to prepare a nanodrug delivery system. According to the preparation results, α-PGA can be used as an ideal drug carrier. Selecting doxorubicin (DOX) as the model drug, an α-PGA/DOX nanoparticle (α-PGA/DOX NPs) with a particle size of 110.4 nm was prepared, and the drug-loading content was 66.2%. α-PGA/DOX NPs presented obvious sustained and pH-dependent release characteristics. The IC50 value of α-PGA/DOX NPs was 1.06 ± 0.77 μg mL−1, decreasing by approximately 8.5 fold in vitro against 4T1 cells after incubation for 48 h. Moreover, α-PGA/DOX NPs enhanced antitumor efficacy in vivo, the tumor inhibition rate was 67.4%, increasing 1.5 fold over DOX injection. α-PGA/DOX NPs also reduced the systemic toxicity and cardiotoxicity of DOX. In sum, α-PGA is a biosafe nanodrug delivery carrier with potential clinical application prospects. [ABSTRACT FROM AUTHOR]

Naringenin (NRG) is a natural flavonoid compound abundantly present in citrus fruits and has the potential to treat respiratory disorders. However, the clinical therapeutic effect of NRG is limited by its low bioavailability due to poor solubility. To enhance the solubility, naringenin nanosuspensions (NRG-NSps) were prepared by applying tocopherol polyethylene glycol succinate (TPGS) as the nanocarrier via the media-milling method. The particle size, morphology, and drug-loading content of NRG-NSps were examined, and the stability was evaluated by detecting particle size changes in different physiological media. NRG-NSps exhibited a flaky appearance with a mean diameter of 216.9 nm, and the drug-loading content was 66.7%. NRG-NSps exhibited good storage stability and media stability. NRG-NSps presented a sustainable release profile, and the cumulative drug-release rate approached approximately 95% within 7 d. NRG-NSps improved the antitussive effect significantly compared with the original NRG, the cough frequency was decreased from 22 to 15 times, and the cough incubation period was prolonged from 85.3 to 121.6 s. Besides, NRG-NSps also enhanced expectorant effects significantly, and phenol red secretion was increased from 1.02 to 1.45 μg/mL. These results indicate that NRG-NSps could enhance the bioavailability of NRG significantly and possess a potential clinical application. [ABSTRACT FROM AUTHOR]

Clarifying the effects of climate warming on seed germination is critical for predicting plant community assembly and species renewal, especially in alpine grassland ecosystems where warming is occurring faster than in other biomes globally. We collected matured seeds of 19 common species from a typical alpine meadow steppe community in Central Tibet. Seeds were germinated in three incubators with manipulated day-night temperatures to impose three treatments: (1) theoretically optimal values of 25/15 °C, (2) temperatures observed in the field (control), and (3) a warming of 3 °C above the observed temperatures. We calculated seed germination percentage (SGP) and mean germination time (MGT) per species at different treatments. Our results showed that SGPs of Stipa capillacea, Kobresia macrantha, Potentilla saundersiana, Saussurea tibetica, Pedicularis kansuensis, and Androsace graminifolia were higher under the warming treatment than under control. Among them, the MGTs of S. capillacea, K. macrantha, and And. graminifolia were significantly shortened, while the MGT of Pe. kansuensis was significantly lengthened by warming of 3 °C. Significant decreases in MGT induced by warming were only observed for Festuca coelestis and Anaphalis xylorhiza. Additionally, the treatment with theoretically optimal temperatures restrained germination of Stipa purpurea, S. capillacea, F. coelestis, and Sa. tibetica seeds but promoted germination of K. macrantha, Astragalus strictus, P. saundersiana, Potentilla bifurca, Pe. kansuensis, Swertia tetraptera, Pleurospermum hedinii, and And. Graminifolia seeds, when compared with the control and warming treatments. Therefore, the response of seed germination to warming differs among alpine species, implying that future warming could result in significant changes in community assembly of alpine grasslands on the Tibetan Plateau. [ABSTRACT FROM AUTHOR]

The allocation of net primary production (NPP) between above- and belowground components is a key step of ecosystem material cycling and energy flows, which determines many critical parameters, e.g., the fraction of below ground NPP (BNPP) to NPP (fBNPP) and root turnover rates (RTR), in vegetation models. However, direct NPP estimation and partition are scarcely based on field measurements of biomass dynamics in the alpine grasslands on the Northern Tibetan Plateau (NTP). Consequently, these parameters are unverifiable and controversial. Here, we measured above- and belowground biomass dynamics (monthly from May to September each year from 2013 to 2015) to estimate NPP dynamics and allocations in four typical alpine grassland ecosystems, i.e., an alpine meadow, alpine meadow steppe, alpine steppe and alpine desert steppe. We found that NPP and its components, above and below ground NPP (ANPP and BNPP), increased significantly from west to east on the NTP, and ANPP was mainly affected by temperature while BNPP and NPP were mainly affected by precipitation. The bulk of BNPP was generally concentrated in the top 10 cm soil layers in all four alpine grasslands (76.1% ± 9.1%, mean ± SD). Our results showed that fBNPP was significantly different among these four alpine grasslands, with its means in alpine meadow (0.93), alpine desert steppe (0.92) being larger than that in the alpine meadow steppe (0.76) and alpine steppe (0.77). Both temperature and precipitation had significant and positive effects on the fBNPP, while their interaction effects were significantly opposite. RTR decreased with increasing precipitation, but increased with increasing temperature across this ecoregion. Our study illustrated that alpine grasslands on the NTP, especially in the alpine meadow and alpine desert steppe, partitioned an unexpected and greater NPP to below ground than most historical reports across global grasslands, indicating a more critical role of the root carbon pool in carbon cycling in alpine grasslands on the NTP. [ABSTRACT FROM AUTHOR]

Oligoethylene glycol dendron (G2) has been used in drug delivery due to its unique dendritic structure and excellent properties. In order to investigate the effects of lipophilic chains on drug delivery, the amphiphilic hybrid compound G2-C18 is synthesized, and celastrol (CSL) is selected to prepare "core-shell" structured CSL-G2-C18 nanoparticles (NPs) via the antisolvent precipitation method. Meanwhile, CSL-G2 NPs are prepared as the control. The two NPs show similar particle sizes and polydispersity indexes, while their morphologies exhibit dramatic differences. CSL-G2 NPs are solid spherical particles, while G2-C18 NPs are vesicles. The two NPs present ideal stability and similar release tendencies. The in vitro toxicity results show that the cell inhibition effect of CSL-loaded NPs is significantly enhanced when compared with free CSL, and the antitumor effect of CSL-G2-C18 NPs is stronger than that of CSL-G2 NPs. The IC 50 value of CSL-G2 NPs and CSL-G2-C18 NPs is enhanced about 2.8-fold and 5-fold when compared with free CSL, respectively. The above results show that lipophilic chain-linking dendritic hybrid nanocarriers promote antitumor activity by affecting the morphology of NPs, which may aid in the selection of carrier designs.

Polypeptide materials have clear secondary structure and biodegradability, which can be further modified and functionalized, so that they can be employed as therapeutic agents in clinical applications. PEGylation of polylysine (PEG-PLL) is a kind of safe and effective nanocarrier that is utilized for gene and drug delivery. However, PEG-PLL needs to be produced through chemical synthesis, which is expensive and difficult to obtain. We hope to simplify the nanocarrier and use hydrophilic natural polylysine (PLL) to develop a high-efficacy delivery system. To evaluate the possibility of PLL as nanocarriers, methotrexate (MTX) is selected as a model drug and PEG-PLL is utilized as control nanocarriers. The experimental results showed that PLL is an ideal polypeptide to prepare MTX-loaded PLL nanoparticles (PLL/MTX NPs). Compared with PEG-PLL as nanocarriers, PLL/MTX NPs showed higher drug-loading content (58.9%) and smaller particle sizes (113.7 nm). Moreover, the shape of PLL/MTX NPs was a unique helical nanorod. The PLL/MTX NPs had good storage stability, media stability, and sustained release effect. Animal research demonstrated that PLL/MTX NPs could improve the anti-tumor activity of MTX, the antitumor efficacy is enhanced 1.9-fold and 1.2-fold compared with MTX injection and PEG-PLL/MTX NPs, respectively. To sum up, natural polymer PLL is an ideal nano drug delivery carrier which has potential clinical applications.