Flavonoid-rich sesame leaf extract-mediated synthesis of nanozymes: Extraction optimization, chemical composition identification and bioactivity evaluation.

Sesame leaves contain rich phenolic acids and flavonoids. However, their potential in nanozyme synthesis has not been investigated yet. Herein, we report the preparation of flavonoid-rich sesame leaf extract (SLE), composition identification, and its use in the construction of iron (Fe)-based nanozymes (Fe-SLE CPNs). SLE was obtained with an extraction yield of ∼14.5% with a total flavonoid content (TFC) of ∼850.85 mg RE/g. There were 83 flavonoid compounds in SLE, primarily including scutellarin, apigenin-7-glucuronid, narcissin, and hyperoside. Fe-SLE CPNs exhibited nanodot morphology with a hydrodynamic size of 79.34 nm and good stability in various physiological solutions, pH levels, and temperatures. The Fe-SLE CPNs were more efficient in the scavenging ability of reactive oxygen species (ROS) than SLE alone. Furthermore, a stronger anti-inflammatory effect of the Fe-SLE CPNs was shown by modulating the MyD88-NF-κB-MAPK signaling pathways. These findings imply that SLE-based nanozymes hold great potential for diverse applications.

Cannabis legalization and hospitalizations in Alberta: Interrupted time series analysis by age and sex.

OBJECTIVES: Recent research has focused on the effects of legalization on cannabis-related emergency department visits, but the considerable healthcare costs of cannabis-related hospitalizations merit attention. We will examine the association between recreational cannabis legalization and cannabis-related hospitalizations. METHODS: A cohort of 3,493,864 adults from Alberta was examined (October 2015-May 2021) over three periods: pre-legalization, post-legalization of flowers and herbs (phase one), and post-legalization of edibles, extracts, and topicals (phase two). Interrupted time series analyses were used to detect changes. RESULTS: The study found an increase in hospitalization rates among younger adults (18-24) before legalization, yet no increased risk was associated with cannabis legalization, for either younger (18-24) or older adults (25+). CONCLUSIONS: Clinicians should be aware of the increased risk in younger groups and may benefit from early identification and intervention strategies, including screening and brief interventions in primary care settings.

Alleviation of cotton growth suppression caused by salinity through biochar is strongly linked to the microbial metabolic potential in saline-alkali soil.

Biochar is a typical soil organic amendment; however, there is limited understanding of its impact on the metabolic characteristics of microorganisms in saline-alkaline soil microenvironment, as well as the advantages and disadvantages of plant-microorganism interactions. To elucidate the mechanisms underlying the impact of saline-alkali stress on cotton, a 6-month pot experiment was conducted, involving the sowing of cotton seedlings in saline-alkali soil. Three different biochar application levels were established: 0 % (C0), 1 % (C1), and 2 % (C2). Results indicated that biochar addition improved the biomass of cotton plants, especially under C2 treatment; the dry weight of cotton bolls were 8.15 times that of C0. Biochar application led to a rise in the accumulation of photosynthetic pigments by 8.30-51.89 % and carbohydrates by 7.4-10.7 times, respectively. Moreover, peroxidase (POD) activity, the content of glutathione (GSH), and ascorbic acid (ASA) were elevated by 23.97 %, 118.39 %, and 48.30 % under C2 treatment, respectively. Biochar caused a reduction in Na+ uptake by 8.21-39.47 %, relative electrical conductivity (REC) of plants, and improved K+/Na+ and Ca2+/Na+ ratio indicating that biochar alleviated salinity-caused growth reduction. Additionally, the application of biochar enhanced the absorption intensity of polysaccharide fingerprints in cotton leaves and roots. Two-factor co-occurrence analysis indicated that the key differential metabolites connected to several metabolic pathways were L-phenylalanine, piperidine, L-tryptophan, and allysine. Interestingly, biochar altered the metabolic characteristics of saline-alkali soil, especially related to the biosynthesis and metabolism of amino acids and purine metabolism. In conclusion, this study demonstrates that biochar may be advantageous in saline soil microenvironment; it has a favorable impact on how plants and soil microbial metabolism interact.

Inhibitory effects and mechanisms of phenolic compounds in rapeseed oil on advanced glycation end product formation in chemical and cellular models in vitro.

Sinapic acid (SA), canolol (CAO) and canolol dimer (CAO dimer) are the main phenolic compounds in rapeseed oil. However, their possible efficacy against glycation remains unclear. This study aims to explore the impacts of these substances on the formation of advanced glycation end products (AGEs) based on chemical and cellular models in vitro. Based on fluorescence spectroscopy results, three chemical models of BSA-fructose, BSA-methylglyoxal (MGO), and arginine (Arg)-MGO showed that SA/CAO/CAO dimer could effectively reduce AGE formation but with different abilities. After SA/CAO/CAO dimer incubation, effective protection against BSA protein glycation was observed and three different MGO adducts were formed. In MGO-induced HUVEC cell models, only CAO and CAO dimer significantly inhibited oxidative stress and cell apoptosis, accompanied by the regulation of the Nrf2-HO-1 pathway. During the inhibition, 20 and 12 lipid mediators were reversed in the CAO and CAO dimer groups compared to the MGO group.

Alterations in the composition and metabolite profiles of the saline-alkali soil microbial community through biochar application.

Saline-alkali soil poses significant chanllenges to sustainable development of agriculture. Although biochar is commonly used as a soil organic amendment, its microbial remediation mechanism on saline-alkali soil requires further confirmation. To address this, we conducted a pot experiment using cotton seedlings to explore the potential remediation mechanism of rice straw biochar (BC) at three different levels on saline-alkaline soil. The results showed that adding of 2% biochar greatly improved the quality of saline-alkaline soil by reducing pH levels, electrical conductivity (EC), and water-soluble ions. Moreover, biochar increased the soil organic matter (SOM), nutrient availability and extracellular enzyme activity. Interestingly, it also reduced soil salinity and salt content in various cotton plant tissues. Additionally, biochar had a notable impact on the composition of the microbial community, causing changes in soil metabolic pathways. Notably, the addition of biochar promoted the growth and metabolism of dominant salt-tolerant bacteria, such as Proteobacteria, Bacteroidota, Acidobacteriota, and Actinobacteriota. By enhancing the positive correlation between microorganisms and metabolites, biochar alleviated the inhibitory effect of salt ions on microorganisms. In conclusion, the incorporation of biochar significantly improves the soil microenvironment, reduces soil salinity, and shows promise in ameliorating saline-alkaline soil conditions.

Plant exosome-like nanovesicles derived from sesame leaves as carriers for luteolin delivery: Molecular docking, stability and bioactivity.

The growing recognition of luteolin (Lu) as a vital functional component is attributed to its notable bioactive properties. However, the effective use of Lu is hindered by its inherent limitations related to water solubility, stability, and bioavailability. Here, we aim to develop sesame leaves-derived exosome-like nanovesicles (Exo) for Lu delivery (Exo@Lu) as vehicles. The encapsulation mechanism, solubility, stability, and bioactivity of Exo@Lu were thoroughly evaluated. Exo enriched abundant lipids, proteins, and phenolic compounds with an encapsulation efficiency of âˆ¼ 91.9 % and a loading capacity of âˆ¼ 20.5 % for Lu. The primary binding forces responsible for the encapsulation were hydrogen bonds and van der Waals forces. After encapsulation, the water solubility and stability of Lu were significantly improved under various conditions, including thermal, light, storage, ionic strength, and pH. Exo@Lu maintained structural integrity during simulated digestion, enhancing bioaccessibility and efficacy in mitigating oxidative stress and inflammatory response compared to Exo and free Lu.

Chemical profile of phenolic extracts from rapeseed meal and inhibitory effects on α-glucosidase: UPLC-MS/MS analysis, multispectral approaches, molecular simulation and ADMET analysis.

Rapeseed meal (RSM) is the by-product of rapeseed processing that enriches phenolic compounds. However, the comprehensive characterization of its phenolic substances in terms of composition and potential activities remains incomplete, leading to limited utilization in the food industry. In this study, the phenolic profile from RSM (referred to as RMP) was identified, and their inhibitory effects on α-glucosidase were investigated. UPLC-MS/MS analysis showed that a total of 466 phenolic compounds were detected in RMP. The primary components were sinapic acid (SA), caffeic acid (CA), salicylic acid (SAA), and astragalin (AS). Multispectral approaches demonstrated significant inhibitory capacity of RMP against α-glucosidase with a half inhibition value (IC50) of 0.32 mg/mL, with a stronger inhibition compared to CA/SAA/AS (IC50: 4.0, 5.9, and 0.9 mg/mL) in addition to the previously reported SA, suggesting a synergistic effect. Both RMP and CA/SAA/AS altered the secondary structure of α-glucosidase to quench its intrinsic fluorescence. Molecular simulation results revealed that hydrogen bonds and van der Waals forces primarily contributed to the interaction between CA/SAA/AS and α-glucosidase, as well as verified the stability of the binding process over the entire simulation duration. The ADMET analysis showed that CYP2D6 was not inhibited by CA/SAA/AS, which had no AMES toxicity, hepatotoxicity, and skin sensitization. This finding suggests the potential of RMP against α-glucosidase for the treatment of diabetes.

Effect of co-application of straw and various nitrogen fertilizers on N2O emission in acid soil.

In order to explore the alteration of N transformation and N2O emissions in acid soil with the co-application of straw and different types of nitrogen (N) fertilizers, an incubation experiment was carried out for 40 days. There are totally five treatments in the study: (a) without straw and N fertilizer (N0), (b) straw alone application (SN0), (c) straw with NH4Cl (SN1), (d) straw with NaNO3 (SN2), and (e) straw with NH4NO3 (SN3). N2O emissions, soil physicochemical properties, and abundance/activity of ammonia-oxidizing archaea (AOA) were measured. The results showed that the combined application of straw and N enhanced N2O emissions, particularly, SN2 and SN3 treatments. Moreover, the soil pH was lower in co-application treatments and the average decreasing rate was 9.69%. Specially, the pH was lowest in the SN1 treatment. The results of correlation analysis indicated a markedly negative relationship between pH and N2O, as well as a negative relationship between pH and net mineralization rate. These findings suggest that pH alteration can affect the N transformation process in soil and thus influence N2O emissions. In addition, the dominant AOA at the genus level in the SN2 treatment was Nitrosopumilus, and Candidatus nitrosocosmicus in the SN3 treatment. The reshaped AOA structure can serve as additional evidence of the changes in the N transformation process. In conclusion, as the return of straw, the cumulation of N2O from arable acid soil depends on the form of N fertilizer. It is also important to consider how N fertilizer is applied to reduce the possibility of N being lost in the soil as gas.

Development and validation of immunogenic cell death-applied prediction model for esophageal carcinoma.

Evidence suggests that immunogenic cell death (ICD) releases cancer antigens that promote cytotoxic T-cell responses, potentially improving immunotherapy. However, the relationship between ICDs and esophageal cancer (EC) remains unclear. This study aimed to determine the role of ICDs in EC and to construct an ICD-based prognostic panel. RNA-seq data of EC and the corresponding clinical information were downloaded from the UCSC-Xena platform to explore the association between ICD gene expression and EC prognosis. The GSE53625 dataset was used to validate the proposed model. Differentially expressed genes (DEGs) between different molecular subtypes were identified to construct a new ICD-related prognosis panel and generate molecular subtypes using ConsensusClusterPlus. We created a prognostic profile based on the ICD and a nomogram based on the risk score. Compared with normal samples, ICD gene expression of malignant samples were significantly increased. 161 patients with EC were successfully divided into three subtypes (SubA, SubB, and SubC). Patients with EC in the SubC group had the best survival and lowest ICD score, whereas patients in the SubB group had the worst prognosis. DEGs between subtypes were evaluated, and risk panels were established using LASSO-Cox regression analysis. The prognosis of low-risk patients was significantly better than that of high-risk patients in both cohorts. The area under the curve of the receiver operating characteristic curve indicated that the risk group had a good prognostic value. Our study identified the molecular subtypes of EC and ICD-based prognostic signatures. Our three-gene risk panel could serve as a biomarker for effectively assessing the prognostic risk of patients with EC.

Iron-modified biochar reduces nitrogen loss and improves nitrogen retention in Luvisols by adsorption and microbial regulation.

Nitrogen (N) loss poses a great threat to global environmental sustainability. The application of modified biochar is a novel strategy to improve soil nitrogen retention and alleviate the negative effects caused by N fertilizers. Therefore, in this study iron modified biochar was used as a soil amendment to investigate the potential mechanisms of N retention in Luvisols. The experiment comprised five treatments i.e., CK (control), 0.5 % BC, 1 % BC, 0.5 % FBC and 1 % FBC. Our results showed that the intensity of functional groups and surface structure of FBC was improved. The 1 % FBC treatment showed a significant increment in soil NO3--N, dissolved organic nitrogen (DON), and total nitrogen (TN) content by 374.7 %, 51.9 %, and 14.4 %, respectively, compared with CK. The accumulation of N in cotton shoots and roots was increased by 28.6 % and 6.6 % with 1 % FBC addition. The application of FBC also stimulated the activities of soil enzymes related to C and N cycling i.e., ß-glucosidase (ßG), ß-Cellobiohydrolase (CBH), and Leucine aminopeptidase (LAP). In the soil treated with FBC, a significant improvement in the structure and functions of the soil bacterial community was found. FBC addition altered the taxa involved in the N cycle by affecting soil chemical properties, especially for Achromobacte, Gemmatimonas, and Cyanobacteriales. In addition to direct adsorption, the regulation of FBC on organisms related to N-cycling also played an important role in soil nitrogen retention.

Hyaluronic acid-functionalized redox-responsive organosilica nanoparticles for targeted resveratrol delivery to attenuate acrylamide-induced toxicity.

The purpose of this study is to construct a redox-responsive and targeted nanoparticle to effectively deliver resveratrol (Res) for alleviating acrylamide (ACR) toxicity. Here, Res-loaded tetrasulfide-containing organosilica nanoparticles (DSMSNs) functionalized with hyaluronic acid on the surface (DSMSNs@Res@HA) were prepared. The DSMSNs@Res@HA nanoparticles were spherical with an encapsulation efficiency of 46.68 ± 1.64 % and a hydrated particle size of about 237.73 nm. As expected, DSMSNs@Res@HA were capable of significantly protecting PC12 cells against ACR-induced damage in oxidative stress, mitochondrial membrane potential decrease, and cell apoptosis compared with free Res and DSMSNs@Res at the equivalent dose. Moreover, DSMSNs@Res@HA could be biodegraded and released Res in response to GSH stimulus. In vivo experiments suggested that DSMSNs@Res@HA significantly reduced histological damage in the brain, liver, and kidney of rats compared with free Res and DSMSNs@Res. After oral administration of DSMSNs@Res@HA, the intestinal flora of ACR-treated rats could be effectively regulated by improving the species uniformity and abundance as well as recovering the species diversity. According to these findings, DSMSNs@Res@HA is worth further investigation as a potential therapeutic nanomedicine to alleviate ACR toxicity and restore gut microbiota diversity.

Inhibitory mechanism of phenolic compounds in rapeseed oil on α-amylase and α-glucosidase: Spectroscopy, molecular docking, and molecular dynamic simulation.

Developing naturally active components to control α-amylase/α-glucosidase activity is highly desired for preventing and managing type 2 diabetes. Rapeseed oil is rich in active phenolic compounds and seed oil is a major source of liposoluble inhibitors to these enzymes. However, it remains unclear about the interaction of phenolic compounds in rapeseed oil with α-amylase/α-glucosidase. This study found that the important phenolic compounds from rapeseed oil (Sinapic acid, SA; canolol, CAO; canolol dimer, CAO dimer) possessed effective inhibition performance against α-amylase and α-glucosidase. CAO showed the lowest and highest inhibitory effect, respectively. In the kinetics studies, the inhibition mechanism of SA/CAO/CAO dimer against α-glucosidase was non-competitive, exhibiting a different way from α-amylase. Fluorescence quenching spectra implied that the static processes were responsible for the spontaneous binding between the compounds and enzymes. Fourier-transform infrared spectroscopy (FT-IR) displayed these compounds-induced conformation alterations of α-amylase/α-glucosidase. Molecular docking revealed that SA/CAO/CAO dimer decreased the catalytic efficiency of α-amylase/α-glucosidase through hydrogen bonds, hydrophobic force, or π-π interaction. Molecular dynamics matched well with the experimental and docking results regarding the inhibitory behaviors and interactions toward α-amylase/α-glucosidase. These results demonstrated the potential benefits of phenolic compounds from rapeseed oil in antidiabetic-related activities.

[Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion].

OBJECTIVES: To investigate the expression of cyclophilin A (CyPA) in oral squamous cell carcinoma (OSCC) and explore the effect of downregulating the expression of CyPA gene on the proliferation and invasion of SCC-25 cells. METHODS: A total of 77 cases of patients with OSCC were selected. The expression levels of CyPA proteins in OSCC and adjacent normal tissues were evaluated. SCC-25 cells were cultured and divided into the CyPA interference sequence group, negative control group, and blank group. The expression levels of CyPA mRNA and protein in cells were detected by using real-time fluorescent quantitative polymerase chain reaction and Western blot, respectively. Cell proliferation was detected by using methyl thiazolyl tetrazolium and plate colony formation assays. Cell invasion was detected by using Transwell assay. RESULTS: The positive expression rate of CyPA protein in OSCC tissues was 76.62%, which was higher than that in adjacent tissues (P<0.05). The positive expression rate of CyPA protein in TNM stage T3+T4, clinical stage Ⅲ+Ⅳ, moderately or poorly differentiated lymph node metastasis was increased (P<0.05). Compared with the negative control and blank groups, the CyPA interference sequence group had decreased relative expression levels of CyPA mRNA and protein (P<0.05); optical density va-lues of cells at 24, 48, 72, and 96 h (P<0.05); and number of cell colonies and invasive cells (P<0.05). CONCLUSIONS: The CyPA protein is highly expressed in OSCC tissues, and the downregulation of CyPA gene expression in SCC-25 cells can reduce cell proliferation and inhibit cell invasion.

Large Scale, Multicenter, Prospective Study of Apatinib in Advanced Gastric Cancer: A Real-World Study from China.

BACKGROUND: In China, gastric cancer (GC) ranks second in incidence and mortality. Over 80% of patients with GC were diagnosed at an advanced stage with poor clinical outcome. Chemotherapy was the mainstream treatment with limited benefit. Apatinib, an inhibitor of targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for third-line treatment of advanced gastric cancer. However, the data of apatinib treatment in the real-world setting are limited. In this real-world study, we aimed to understand the current treatment pattern of apatinib, investigate the effectiveness and safety of apatinib in real-world settings, and explore the potential factors associated with the clinical outcomes. METHODS: This was a prospective, multicenter observational study in a real-world setting. Patients aged ≥18 years with histologic diagnosis of advanced GC were eligible for enrollment. The eligible patients received either apatinib monotherapy or apatinib plus chemotherapy by physician's discretion. Apatinib treatment could be used as first-line, second-line, or third-line and above therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), ORR, DCR, and safety profile. RESULTS: A total of 737 patients with advanced gastric cancer treated with apatinib were included in the FAS population. A total of 54.9% patients used apatinib monotherapy and 45.1% patients used apatinib combination therapy. A total of 44.1% patients received apatinib in first-line treatment, 28.2% in second-line, and 27.7% in third-line and above. In first-line treatment, the objective response rate (ORR) was 9.09% and 16.42% in apatinib monotherapy and combination therapy groups, and disease control rate (DCR) was 78.41% and 89.29%, respectively. Patients who received combination therapy achieved significantly longer median progression-free survival (mPFS; 6.18 vs 3.52 months, p<0.01) and median overall survival (mOS; 8.72 vs 5.92 months, p<0.01) compared with monotherapy. In second-line and third-line therapy, combination therapy showed a better trend in tumor response and survival outcomes compared with monotherapy. For all patients, apatinib combined with paclitaxel were associated with longer mPFS compared with other combinations (8.88 vs 6.62 months). Multivariate analysis showed that combination with paclitaxel (p=0.02) and experience of apatinib-related specific AEs (p<0.01) were independent predictors for PFS and OS. The safety profile was tolerable and no unexpected adverse events were reported. CONCLUSION: In a real-world setting, apatinib showed a favorable effectiveness and safety profile in patients with advanced gastric cancer. Apatinib combination therapy, especially combined with paclitaxel, might lead to better survival benefit in first-line treatment. Combination with paclitaxel and the occurrence of apatinib-specific AEs were independent factors associated with better survival outcomes. TRIAL REGISTRATION: NCT03333967.

Dietary canolol induces apoptosis in human cervical carcinoma HeLa cells through ROS-MAPK mediated mitochondrial signaling pathway: In vitro and in vivo.

Canolol (4-vinylsyringol), extracted form crude canola oil, is the promising drug toward cancer prevention and treatment. The current studies focus on the role of COX-2 signaling pathway in canolol-induced apoptosis in cancer cells. It is still unknown whether mitochondria and MAPK signaling pathways are involved. To elucidate the roles of above signaling pathways in canolol-induced apoptosis in cancer cells, human cervical carcinoma cell line HeLa and HeLa xenograft tumor model are adopted. Canolol induced apoptosis of HeLa cells and inhibited tumor growth with low systemic adverse effect, accompanying with excess generation of intracellular ROS and lysosome rupture. The results in vitro and in vivo confirmed that MAPK signaling pathways mediated mitochondrial signaling pathway activation were involved in canolol-induced apoptosis. In conclusion, these data showed that canolol induced apoptosis in HeLa cells through ROS-MAPK mediated mitochondrial signaling pathway, providing a view of the potential application of canolol as an anticancer agent.

A cationic conjugated polymer and graphene oxide: Application to amplified fluorescence detection of sinapine.

An amplified fluorescence strategy is described for the detection of sinapine (SP) by using a cationic conjugated polymer (PFP) and graphene oxide (GO). It is observed that the fluorescein (FAM)-labeled single-stranded DNA (FAM-DNA) is absorbed on the surface of GO if SP is absent. This causes that fluorescence resonance energy transfer (FRET) from PFP to FAM is inefficient when adding PFP into FAM-DNA/GO complex. If SP is added to FAM-DNA/GO complex, FAM-DNA is desorbed from GO surface due to the competitive binding of SP and FAM-DNA toward GO. In this case, FAM-DNA is close to PFP in the presence of PFP through strong electrostatic interaction, leading to the occurrence of efficient FRET. Based on the above phenomenon, we demonstrate a method to amplify fluorescence signal of traditional GO-based SP assay by introducing PFP. In comparison to the use of single GO, the combination of PFP with GO-based strategy displays high turn-on ratio and enhanced sensitivity with a limit of detection as low as 7.3 ng mL-1 for SP detection. Satisfactory results in practical samples are also obtained by the recovery experiments, demonstrating the potential application of cationic conjugated polymer in plant-derived small molecule.

Dietary polyphenol canolol from rapeseed oil attenuates oxidative stress-induced cell damage through the modulation of the p38 signaling pathway.

Canolol (CAO) is a main phenolic compound with remarkable antioxidative properties that is generated in rapeseed oil during microwave pressing. The objective of this study was to identify the protective effect of CAO in hydrogen peroxide (H2O2)-triggered oxidative stress and reveal the role of the p38 MAPK pathway during the protective process. CAO treatment showed an observable cytoprotective effect. Results showed that CAO significantly improved H2O2-stimulated cell death, and diminished ROS production and malondialdehyde (MDA) level. Moreover, CAO increased glutathione (GSH) content and promoted the activities of superoxide dismutase (SOD) and catalase (CAT). As a result, apoptosis was ameliorated and depletion of the mitochondrial membrane potential was restored. Western blotting analysis demonstrated CAO downregulated the expression of caspase-3 and decreased the ratio of Bax/Bcl-2. Notably, the phosphorylation of p38 MAPK was inhibited by CAO in H2O2-induced apoptosis, which was confirmed by its inhibitor (SB203580). Taken together, our study demonstrated the pivotal role of the p38 MAPK pathway in the cytoprotective effect of CAO on oxidative stress-induced cell damage, suggesting CAO is a promising antioxidant in food and health-related fields.

A tellurylsulfide bond-containing redox-responsive superparamagnetic nanogel with acid-responsiveness for efficient anticancer therapy.

A tellurylsulfide bond-containing biopolymer nanogel was first fabricated to achieve smart drug release. The reductive nanogel exhibited highly sensitive reduction-responsiveness, fast internalization, and efficient anticancer therapy. This approach displays a new potential of tellurylsulfide bond-containing nanocarriers for drug delivery.

Selenylsulfide Bond-Launched Reduction-Responsive Superparamagnetic Nanogel Combined of Acid-Responsiveness for Achievement of Efficient Therapy with Low Side Effect.

With the objective to achieve in-between reduction-responsive drug release, selenylsulfide bond was first explored as a reduction cleavable linkage, compared with the most commonly employed disulfide and diselenide bonds. The reductive nanogel, with a combination of superparamagnetic and acid responsiveness, was fabricated. The expected release profiles were testified. Cytotoxicity assays illustrated the remarkable inhibition to the growth of HeLa cells, in contrast, high tolerance to L02 cells. In vivo investigation exhibited the obvious shrinkage in tumor but a healthy appearance. Hematoxylin-eosin staining and histological examination revealed the lower toxicity. The complex nanogels would have appeared highly promising in cancer therapy.

Carbon monoxide in an extremely metal-poor galaxy.

Extremely metal-poor galaxies with metallicity below 10% of the solar value in the local universe are the best analogues to investigating the interstellar medium at a quasi-primitive environment in the early universe. In spite of the ongoing formation of stars in these galaxies, the presence of molecular gas (which is known to provide the material reservoir for star formation in galaxies such as our Milky Way) remains unclear. Here we report the detection of carbon monoxide (CO), the primary tracer of molecular gas, in a galaxy with 7% solar metallicity, with additional detections in two galaxies at higher metallicities. Such detections offer direct evidence for the existence of molecular gas in these galaxies that contain few metals. Using archived infrared data, it is shown that the molecular gas mass per CO luminosity at extremely low metallicity is approximately one-thousand times the Milky Way value.