Effect of Plateau pika on Soil Microbial Assembly Process and Co-Occurrence Patterns in the Alpine Meadow Ecosystem.

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.

Research on drought stress in Medicago sativa L. from 1998 to 2023: a bibliometric analysis.

Alfalfa (Medicago sativa L.) is one of the most important forage crops in the world. Drought is recognized as a major challenge limiting alfalfa production and threatening food security. Although some literature reviews have been conducted in this area, bibliometric reviews based on large amounts of published data are still lacking. In this paper, a bibliometric analysis of alfalfa drought stress from 1998-2023 was conducted using the Web of Science Core Collection database in order to assess global trends in alfalfa drought stress research and to provide new directions for future research. The results showed that the annual publication output maintained an increase in most years, with China and the United States contributing significantly to the field. Most of the journals published are specialized journals in botany, environmental science, soil science and crop science, as well as related agribusiness journals. "plant growth" and "yield" were the most frequently used keywords, reflecting the important purpose of research in this field. And two main research directions were identified: research on drought response mechanism of alfalfa and exploration of drought-resistant technology. In addition, physiological, biochemical, and molecular responses of drought tolerance and high yield in alfalfa, transgenics, and microbial fertilizer research have been hot research topics in recent years and may continue in the future. The ultimate goal of this paper is to provide a foundational reference for future research on alfalfa's drought resistance and yield optimization mechanisms, thereby enhancing the crop's application in agricultural production.

Nanoparticle-Mediated Synergistic Chemoimmunotherapy for Cancer Treatment.

Until now, there has been a lack of effective strategies for cancer treatment. Immunotherapy has high potential in treating several cancers but its efficacy is limited as a monotherapy. Chemoimmunotherapy (CIT) holds promise to be widely used in cancer treatment. Therefore, identifying their involvement and potential synergy in CIT approaches is decisive. Nano-based drug delivery systems (NDDSs) are ideal delivery systems because they can simultaneously target immune cells and cancer cells, promoting drug accumulation, and reducing the toxicity of the drug. In this review, we first introduce five current immunotherapies, including immune checkpoint blocking (ICB), adoptive cell transfer therapy (ACT), cancer vaccines, oncolytic virus therapy (OVT) and cytokine therapy. Subsequently, the immunomodulatory effects of chemotherapy by inducing immunogenic cell death (ICD), promoting tumor killer cell infiltration, down-regulating immunosuppressive cells, and inhibiting immune checkpoints have been described. Finally, the NDDSs-mediated collaborative drug delivery systems have been introduced in detail, and the development of NDDSs-mediated CIT nanoparticles has been prospected.

The Remarkable Anti-Breast Cancer Efficacy and Anti-Metastasis by Multifunctional Nanoparticles Co-Loading Squamocin, R848 and IR 780.

Background: Breast cancer is a heterogeneous disease globally accounting for approximately 1 million new cases annually. Chemotherapy remains the main therapeutic option, but the antitumor efficacy needs to be improved. Methods: Two multifunctional nanoparticles were developed in this paper using oleic acid and mPEG2k-PCL2k as the drug carriers. Squamocin (Squ) was employed as a chemotherapeutic agent. Resiquimod (R848) or ginsenoside Rh2 was co-encapsulated in the nanoparticles to remold the immunosuppressive tumor microenvironment, and IR780 was coloaded as a photosensitizer to realize photothermal therapy. Results: The obtained Squ-R848-IR780 nanoparticles and Squ-Rh2-IR780 nanoparticles were uniformly spherical and approximately (162.200 ± 2.800) nm and (157.300 ± 1.1590) nm, respectively, in average diameter, with good encapsulation efficiency (above 85% for each drug), excellent stability in various physiological media and high photothermal conversion efficiency (24.10% and 22.58%, respectively). After intravenous administration, both nanoparticles quickly accumulated in the tumor and effectively enhanced the local temperature of the tumor to over 45 °C when irradiated by an 808 nm laser. At a low dose of 0.1 mg/kg, Squ nanoparticles treatment alone displayed a tumor inhibition rate of 55.28%, pulmonary metastasis inhibition rate of 59.47% and a mean survival time of 38 days, which were all higher than those of PTX injection (8 mg/kg) (43.64%, 25 days and 37.25%), indicating that Squ was a potent and effective antitumor agent. Both multifunctional nanoparticles, Squ-Rh2-IR780 nanoparticles and Squ-R848-IR780 nanoparticles, demonstrated even better therapeutic efficacy, with tumor inhibition rates of 90.02% and 97.28%, pulmonary metastasis inhibition rates of 95.42% and 98.09, and mean survival times of 46 days and 52 days, respectively. Conclusion: The multifunctional nanoparticles coloaded with squamocin, R848 and IR 780 achieved extraordinary therapeutic efficacy and excellent antimetastasis activity and are thus promising in the future treatment of breast tumors and probably other tumors.

Enhanced anti-glioma activity of annonaceous acetogenins based on a novel liposomal co-delivery system with ginsenoside Rh2.

Annonaceous acetogenins (ACGs) have potent anti-tumor activity, and the problems of their low solubility, hemolysis, and in vivo delivery have been solved by encapsulation into nanoparticles. However, the high toxicity still limits their application in clinic. In this paper, the co-delivery strategy was tried to enhance the in vivo anti-tumor efficacy and reduce the toxic effects of ACGs. Ginsenoside Rh2, a naturally derived biologically active compound, which was reported to have synergistic effect with paclitaxel, was selected to co-deliver with ACGs. And due to its similarity with cholesterol in chemical structure, the co-loading liposomes, (ACGs + Rh2)-Lipo, were successfully constructed using Rh2 instead of cholesterol as the membrane material. The obtained (ACGs + Rh2)-Lipo and ACGs-Lipo had similar mean particle size (about 80 nm), similar encapsulation efficiency (EE, about 97%) and good stability. The MTS assay indicated that (ACGs + Rh2)-Lipo had stronger toxicity in vitro. In the in vivo study, in contrast to ACGs-Lipo, (ACGs + Rh2)-Lipo demonstrated an improved tumor targetability (3.3-fold in relative tumor targeting index) and significantly enhanced the antitumor efficacy (tumor inhibition rate, 72.9 ± 5.4% vs. 60.5 ± 5.4%, p < .05). The body weight change, liver index, and spleen index of tumor-bearing mice showed that Rh2 can attenuate the side effects of ACGs themselves. In conclusion, (ACGs + Rh2)-Lipo not only alleviated the toxicity of ACGs to the organism, but also enhanced their anti-tumor activity, which is expected to break through their bottleneck.

Simple preparation and greatly improved oral bioavailability: The supersaturated drug delivery system of quercetin based on PVP K30.

Quercetin, as a representative flavonoid, is widely present in daily diet and has been developed as a dietary supplement due to its beneficial physiological activities. However, the application of quercetin is limited due to its poor water solubility and extensive metabolism. So far, the nano-drug delivery systems designed to improve its bioavailability generally have the shortcomings of low drug loading content and difficulty in industrial production. In order to tackle these problems, quercetin supersaturated drug delivery system (QSDDS) was successfully prepared using solvent method, for which PVP K30 was employed as a crystallization and precipitation inhibitor to maintain the supersaturated state of quercetin in aqueous system. The obtained QSDDS, with a relative high drug loading content of 13%, could quickly disperse in water and form colloidal system with the mean particle size of about 200 nm, meanwhile induce the generation of supersaturated quercetin solution more than 12 h. In vivo pharmacokinetic study proved that QSDDS achieved a high absolute bioavailability of 36.05%, 10 times as that of physical quercetin suspension, which was dose-dependent with higher bioavailability at higher dose. Considering the simple preparation method, QSDDS provided a feasible strategy and a simple way to improve oral absorption of insoluble flavonoids.

Effect of aridity on the ß-diversity of alpine soil potential diazotrophs: insights into community assembly and co-occurrence patterns.

Microbial diversity plays a vital role in the maintenance of ecosystem functions. However, the current understanding of mechanisms that shape microbial diversity along environmental gradients at broad spatial scales is relatively limited, especially for specific functional groups, such as potential diazotrophs. Here, we conducted an aridity-gradient transect survey from 60 sites across the Tibetan Plateau, the largest alpine ecosystem of the planet, to investigate the ecological processes (e.g., local species pools, community assembly processes, and co-occurrence patterns) that underlie the ß-diversity of alpine soil potential diazotrophic communities. We found that aridity strongly and negatively affected the abundance, richness, and ß-diversity of soil diazotrophs. Diazotrophs displayed a distance-decay pattern along the aridity gradient, with organisms living in lower aridity habitats having a stronger distance-decay pattern. Arid habitats had lower co-occurrence complexity, including the number of edges and vertices, the average degree, and the number of keystone taxa, as compared with humid habitats. Local species pools explained limited variations in potential diazotrophic ß-diversity. In contrast, co-occurrence patterns and stochastic processes (e.g., dispersal limitation and ecological drift) played a significant role in regulating potential diazotrophic ß-diversity. The relative importance of stochastic processes and co-occurrence patterns changed with increasing aridity, with stochastic processes weakening whereas that of co-occurrence patterns enhancing. The genera Geobacter and Paenibacillus were identified as keystone taxa of co-occurrence patterns that are associated with ß-diversity. In summary, aridity affects the co-occurrence patterns and community assembly by regulating soil and vegetation characteristics and ultimately shapes the ß-diversity of potential diazotrophs. These findings highlight the importance of co-occurrence patterns in structuring microbial diversity and advance the current understanding of mechanisms that drive belowground communities.IMPORTANCERecent studies have shown that community assembly processes and species pools are the main drivers of ß-diversity in grassland microbial communities. However, co-occurrence patterns can also drive ß-diversity formation by influencing the dispersal and migration of species, the importance of which has not been reported in previous studies. Assessing the impact of co-occurrence patterns on ß-diversity is important for understanding the mechanisms of diversity formation. Our study highlights the influence of microbial co-occurrence patterns on ß-diversity and combines the drivers of community ß-diversity with drought variation, revealing that drought indirectly affects ß-diversity by influencing diazotrophic co-occurrence patterns and community assembly.

Ochratoxin A: Overview of Prevention, Removal, and Detoxification Methods.

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.

A γ-Glutamyl Transpeptidase (GGT)-Triggered Charge Reversal Drug-Delivery System for Cervical Cancer Treatment: In Vitro and In Vivo Investigation.

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.

Festuca coelestis Increases Drought Tolerance and Nitrogen Use via Nutrient Supply-Demand Relationship on the Qinghai-Tibet Plateau.

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.

Ginsenoside Rb1 stabilized and paclitaxel / protopanaxadiol co-loaded nanoparticles for synergistic treatment of breast tumor.

Ginsenosides are the major and key components for ginseng to exert its wide and beneficial therapeutic efficacy in clinic. Meanwhile, many ginsenosides and their metabolites showed in vitro an in vivo anti-tumor activity, among which ginsenoside Rb1 has attracted much attention due to its good solubility and amphipathy. In this study, the self-assembly behavior of Rb1 was investigated and the Rb1 nano-assembly could further stabilize or encapsulated hydrophobic drugs such as protopanaxadiol (PPD) and paclitaxel (PTX) to form nanoparticles, based on which, a natural nanoscale drug delivery system, ginsenoside Rb1 stabilized and PTX/PPD co-loaded nanoparticles (GPP NPs) were prepared. The resultant GPP NPs exhibited a small particle size of 126.2 nm, a narrow size distribution (PDI=0.145), and a zeta potential of -27.3 mV. PTX loading content was 11.06% with an encapsulation efficiency of 93.86%. GPP NPs were spherical and stable in normal saline, 5% glucose, PBS, plasma, or on-shelf storage for 7 days. Both PTX and PPD existed in an amorphous state in GPP NPs and were released in a sustained pattern. GPP NPs showed 10-fold higher in vitro anti-tumor activity of than PTX injections. In the in vivo experiment, GPP NPs achieved a much higher tumor inhibition rate than PTX injections (64.95% vs 43.17%, P < 0.01) and certain tumor target ability. In conclusion, GPP NPs had significantly enhanced anti-tumor efficacy and improved tumor microenvironment, thus were promising to be developed into a novel anti-tumor agent for the treatment of breast tumor.

Thermal ablation of hepatic hemangioma: A multi-center experience with long-term outcomes.

BACKGROUND: Thermal ablation, currently used extensively for liver tumors, also has been applied. successfully to hepatic hemangioma; however, it is still considered experimental because previous studies have comprised small sample sizes with short follow-up periods. PURPOSE: We aimed to investigate the effectiveness, safety, and long-term outcomes of thermal ablation for hepatic hemangioma. MATERIALS AND METHODS: From October 2011 to February 2021, the data of 357 patients with 378 hepatic hemangiomas treated by thermal ablation at six hospitals were analyzed in this retrospective study. The technical success, safety, and long-term follow-up results were analyzed. RESULTS: A total of 252 patients (mean age, 49.2 ± 10.5 years) with 273 subcapsular hemangiomas underwent laparoscopic thermal ablation, whereas 105 patients with 105 hemangiomas located in the liver parenchyma underwent CT-guided percutaneous ablation. Of the 378 hepatic hemangiomas (5.0-21.2 cm), 369 lesions were subjected to one session of ablation, while 9 lesions were subjected to two sessions of ablation. Technical success was achieved in 100.0% of cases. Complete ablation was achieved in 361 of 378 hemangiomas (95.5%), while 17 hemangiomas (4.5%) were incompletely ablated, showing subtle enhancement at the peripheral rim. The major complication rate was 2.0% (7/357). The median follow-up period was 67 months (range, 12-124 months). Of the 224 patients with hemangioma-related symptoms, 216 demonstrated complete disappearance of symptoms (96.4%), while 8 were ameliorated (3.6%). Ablated lesion shrinkage was progressive, and 11.4% of hemangiomas almost completely disappeared over time (P < 0.01). CONCLUSION: With a reasonable ablation strategy and comprehensive treatment measurements, thermal ablation could be a safe, feasible, and effective treatment option for hepatic hemangioma.

Characteristics and drivers of plant C, N, and P stoichiometry in Northern Tibetan Plateau grassland.

Understanding vegetation C, N, and P stoichiometry helps us not only to evaluate biogeochemical cycles and ecosystem functions but also to predict the potential impact of environmental change on ecosystem processes. The foliar C, N, and P stoichiometry in Northern Tibetan grasslands, especially the controlling factors, has been highlighted in recent years. In this study, we have collected 340 plant samples and 162 soil samples from 54 plots in three grassland types, with the purpose of evaluating the foliar C, N, and P stoichiometry and underlying control factors in three grassland types along a 1,500-km east-to-west transect in the Northern Tibetan Plateau. Our results indicated that the averaged foliar C, N, and P concentrations were 425.9 ± 15.8, 403.4 ± 22.2, and 420.7 ± 30.7 g kg-1; 21.7 ± 2.9, 19.0 ± 2.3, and 21.7 ± 5.2 g kg-1; and 1.71 ± 0.29, 1.19 ± 0.16, and 1.59 ± 0.6 g kg-1 in the alpine meadow (AM), alpine steppe (AS), and desert steppe (DS) ecosystems, respectively. The foliar C and N ratios were comparable, with values of 19.8 ± 2.8, 20.6 ± 1.9, and 19.9 ± 5.8 in the AM, AS, and DS ecosystems, respectively. Both the C/P and N/P ratios are the lowest in the AM ecosystem, with values of 252.2 ± 32.6 and 12.8 ± 1.3, respectively, whereas the highest values of 347.3 ± 57.0 and 16.2 ± 3.2 were obtained in the AS ecosystem. In contrast, the soil C, N, C/P, and N/P values decreased from the AM to DS ecosystem. Across the whole transects, leaf C, N, and P stoichiometry showed no obvious trend, but soil C and N concentrations showed an increasing trend, and soil P concentrations showed a decreasing trend with the increasing longitude. Based on the general linear model analysis, the vegetation type was the dominant factor controlling the leaf C, N, and P stoichiometry, accounting for 42.8% for leaf C, 45.1% for leaf N, 35.2% for leaf P, 52.9% for leaf C/N, 39.6% for leaf C/P, and 48.0% for leaf N/P; the soil nutrients and climate have relatively low importance. In conclusion, our results supported that vegetation type, rather than climatic variation and soil nutrients, are the major determinants of north Tibet grassland leaf stoichiometry.

Effects of different conformations of polylysine on the anti-tumor efficacy of methotrexate nanoparticles.

Drug delivery systems require that carrier materials have good biocompatibility, degradability, and constructability. Poly(amino acids), a substance with a distinctive secondary structure, not only have the basic features of the carrier materials but also have several reactive functional groups in the side chain, which can be employed as drug carriers to deliver anticancer drugs. The conformation of isomers of drug carriers has some influence on the preparation, morphology, and efficacy of nanoparticles. In this study, two isomers of polylysine, including ε-polylysine (ε-PL) and α-polylysine (α-PL), were used as drug carriers to entrap methotrexate (MTX) and construct nano-drug delivery systems. ε-PL/MTX nanoparticles with the morphology of helical nanorods presented a small particle size (115.0 nm), and relative high drug loading content (57.8 %). The anticancer effect of ε-PL/MTX nanoparticles was 1.3-fold and 2.6-fold stronger than that of α-PL/MTX nanoparticles in vivo and in vitro, respectively. ε-PL is an ideal drug carrier with potential clinical application prospects.

Study on prevention and control measures of sandstone geothermal reinjection plugging.

In the process of geothermal tailwater reinjection of sandstone, the problem of plugging has been seriously restricting the continuous development of geothermal reinjection for many years, and the problems of plugging are complex and changeable. The plugging in the process of reinjection can be divided into physical plugging, chemical plugging, microbial plugging and gas plugging. Given these four types of blocking, according to the mechanism characteristics of the blocking caused by them, this paper puts forward corresponding blocking prevention measures and solves the current blocking problems by filtering, adding a scale inhibitor, intermittent reinjection, adding chlorine dioxide and regular lifting. In addition, the existing reinjection process and the equipment flow are relatively simple and cannot achieve the goal of efficient reinjection. Therefore, a complete set of reinjection processes is designed to ensure the efficient reinjection of sandstone geothermal tailwater.

Mitochondrial-Targeted Triphenylphosphonium-Hydroxycamptothecin Conjugate and Its Nano-Formulations for Breast Cancer Therapy: In Vitro and In Vivo Investigation.

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.

A Celastrol Drug Delivery System Based on PEG Derivatives: The Structural Effects of Nanocarriers.

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.

Combined Photothermal Therapy and Lycium barbarum Polysaccharide for Topical Administration to Improve the Efficacy of Doxorubicin in the Treatment of Breast Cancer.

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.

Hydrophilic Natural Polylysine as Drug Nanocarrier for Preparation of Helical Delivery System.

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.

Response of under-ground bud bank to degradation in an alpine meadows on the Qinghai-Tibet Plateau, China.

Exploring the diversity and formation mechanism of under-ground bud banks is essential for understanding the renewal of plant populations and community succession. However, there are few studies on the response of bud bank size and composition to different degradation gradients in alpine meadows. In view of this, we investigated the size and composition of bud bank under four degradation gradients (non-degraded:ND, lightly degraded:LD, moderately degraded:MD, and heavily degraded:HD) caused by overgrazing in a typical alpine meadow in Tibet, China, using a unit area excavation sampling method, and analyzed the correlation between above-ground plant community composition and bud bank density. Our results showed that: (i) in the ND alpine meadow, rhizome buds were dominant, in the LD, tiller buds were dominant, and in the MD, root-sprouting buds were dominant; (ii) total bud bank and cyperaceae bud density decreased with increasing degradation gradient, the density of leguminosae was insignificant in each degradation gradient, and the density of gramineae and forb were dominant in LD and MD meadows, respectively; (iii) total bud bank density was significantly and positively correlated with total above-ground biomass in the LD gradient, tiller bud density was significantly positively correlated with the species diversity index of above-ground vegetation under the ND gradient, rhizome bud density was significantly and positively correlated with total above-ground biomass in the LD gradient, and root-sprouting density was significantly negatively correlated with total above-ground biomass in ND meadows, but was significantly positively correlated with the species diversity index of the LD gradient. Therefore, our research shows that rhizome buds are more important in ND meadow habitats, tiller buds are more important in LD meadow habitats, and root-sprouting buds are more important in MD meadows. The response of bud banks to degradation gradient varies with different types of bud banks and different functional groups of plants, and the survival strategy of bud banks is of great value for community restoration and regeneration, which should be paid more attention to in subsequent alpine meadow research.