Preparation and characterization of biochar from four different solid wastes and its ampicillin adsorption performance.

The integration of biochar (BC) production from organic waste with ampicillin (AMP), an emerging pollutant, adsorption is a novel and promising treatment approach. In this study, peanut shells, coffee grounds, digestates, and oyster shells were used for BC production. Among these, the use of anaerobic digestate from food waste fermentation to produce extracts for antibiotic adsorption is relatively unexplored. The pyrolysis temperature was determined using thermogravimetric analysis (TGA) and the materials were characterized with BET, SEM, FTIR, and XRD. The TGA results indicate that PSB, CRB, and DSB underwent pyrolysis involving cellulose, hemicellulose, and lignin, whereas OSB underwent crystal formation. Characterization revealed that DSB has more functional groups, a superior mesoporous structure, appropriate O/C ratio, and trace amounts of calcite crystals, which are favorable for AMP adsorption. Adsorption experiments demonstrate that all four materials adhere to the Freundlich and Langmuir isotherm and Elovich kinetic models, indicating predominant physical adsorption, with some chemical adsorption also present. Thermodynamic studies demonstrate that BC is spontaneous during adsorption and is a heat-absorbing reaction. DSB exhibits the strongest AMP adsorption. A 53.81 mg g-1 adsorbance was obtained at a dosage of 150 mg, pH = 2, and 60 °C. This study introduces innovative approaches for managing waste types and provides data to support the selection of suitable solid wastes for the preparation of BC with excellent adsorption properties. Furthermore, it lays the groundwork for future studies aimed at enhancing the AMP treatment efficacy.

Unveiling the Pharmacological Mechanisms of Davidiin's Anti-Diabetic Efficacy in Streptozotocin-Treated Rats: A Comprehensive Analysis of Serum Metabolome.

Background: Polygonum capitatum Buch.-Ham. ex D. Don (P. capitatum), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties. Materials and Methods: Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS. Results: Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins. Conclusion: Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin's action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.

Systematic DOE Approach for Dry Granulation Study at Early Clinical Stage of Novel Drugs: An Industrial Case.

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

Korean red ginseng formula attenuates non-alcoholic fatty liver disease in oleic acid-induced HepG2 cells and high-fat diet-induced rats.

Objective: Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease. We have developed a Korean Red Ginseng Formula (KRGF) containing extracts of Korean Red Ginseng (KRG), Crataegus Fructus, and Cassiae Semen. In this study, our aims were to investigate the therapeutic potential and underpinning mechanisms of KRGF in NAFLD complicated by hyperlipidemia. Methods: In the in vitro assays, HepG2 cells were treated with KRGF for 24 h in the presence or absence of oleic acid (OA). To assess the in vivo protective effect of KRGF against NAFLD, rats fed a high-fat diet (HFD) were given intragastric administration for 30 days. Results: KRGF exerted protective effects against NAFLD by reducing lipid accumulation and steatosis in OA-stimulated HepG2 cells and HFD-fed rats. In HFD-fed rats, KRGF effectively decreased triglyceride levels in both blood and liver tissue and modulated the expression of key regulators of lipogenesis and fatty acid oxidation. KRGF downregulated the expression of lipogenesis factors, namely C/EBPα, FAS, SREBP-1c, and PPARγ, while upregulating the expression of PPARα and CPT-1, thus promoting fatty acid oxidation. Additionally, KRGF intensified the phosphorylation of AMPK and ACC, which are two enzymes that suppress fatty acid synthesis and promote fatty acid oxidation. KRGF effectively decreased total cholesterol (TC) levels in both blood and liver tissue, and it modulated the expression of major enzymes related to TC metabolism, namely apoB, ACAT2, CYP7A1, and HMGCR. Conclusion: In conclusion, KRGF mitigated NAFLD complicated by hyperlipidemia by modulating triglyceride and cholesterol metabolism, suggesting its potential for future development in the treatment of NAFLD.

Chaihu-Guizhi-Ganjiang Decoction is more efficacious in treating irritable bowel syndrome than Dicetel according to metabolomics analysis.

BACKGROUND: Chaihu-Guizhi-Ganjiang Decoction (CGGD) is a traditional Chinese medicine (TCM) prescription used to treat viral influenza. There is evidence that CGGD can be used to treat irritable bowel syndrome (IBS) but the potential mechanism of action and metabolites produced upon CGGD treatment remains elusive. METHODS: Patients with IBS were treated with pinaverium bromide (Dicetel™) and then CGGD after a washout period of 1 week. Both treatments lasted for 30 days. The efficacy and changes of metabolites in plasma after the two treatments were compared. Plasma samples were acquired before and after each treatment, and untargeted metabolics analysis was performed. RESULTS: Efficacy was measured according to the Rome IV criteria and TCM theory. Our results indicated that CGGD showed significantly better efficacy than Dicetel in the treatment of IBS utilizing each criterion. CGGD exerted greater effects on plasma metabolism than Dicetel. Dicetel treatment led to increased tryptophan metabolism (increased levels of 5-Hydroxyindoleacetaldehyde) and increased protein metabolism (increased levels of L-arginine). CGGD treatment significantly (p < 0.05) increased carnitine metabolism, with elevated levels of L-carnitine and acylcarnitine in plasma. Such changes in these metabolites could exert effects against IBS by improving gastrointestinal motility and suppressing pain, depression, and inflammation. CONCLUSIONS: CGGD appeared to be more efficacious than Dicetel for treating patients with IBS. The findings provide a sound support for the underlying biomolecular mechanism of CGGD in the prevention and treatment of IBS.

Corrigendum: Integrated chemical interpretation and network pharmacology analysis to reveal the anti-liver fibrosis effect of Penthorum chinense.

[This corrects the article DOI: 10.3389/fphar.2022.788388.].

Integrated Chemical Interpretation and Network Pharmacology Analysis to Reveal the Anti-Liver Fibrosis Effect of Penthorum chinense.

Liver fibrosis is a disease with complex pathological mechanisms. Penthorum chinense Pursh (P. chinense) is a traditional Chinese medicine (TCM) for liver injury treatment. However, the pharmacological mechanisms of P. chinense on liver fibrosis have not been investigated and clarified clearly. This study was designed to investigate the chemicals in P. chinense and explore its effect on liver fibrosis. First, we developed a highly efficient method, called DDA-assisted DIA, which can both broaden mass spectrometry (MS) coverage and MS2 quality. In DDA-assisted DIA, data-dependent acquisition (DDA) and data-independent acquisition (DIA) were merged to construct a molecular network, in which 1,094 mass features were retained in Penthorum chinense Pursh (P. chinense). Out of these, 169 compounds were identified based on both MS1 and MS2 analysis. After that, based on a network pharmacology study, 94 bioactive compounds and 440 targets of P. chinense associated with liver fibrosis were obtained, forming a tight compound-target network. Meanwhile, the network pharmacology experimental results showed that multiple pathways interacted with the HIF-1 pathway, which was first identified involved in P. chinense. It could be observed that some proteins, such as TNF-α, Timp1, and HO-1, were involved in the HIF-1 pathway. Furthermore, the pharmacological effects of P. chinense on these proteins were verified by CCl4-induced rat liver fibrosis, and P. chinense was found to improve liver functions through regulating TNF-α, Timp1, and HO-1 expressions. In summary, DDA-assisted DIA could provide more detailed compound information, which will help us to annotate the ingredients of TCM, and combination with computerized network pharmacology provided a theoretical basis for revealing the mechanism of P. chinense.

Bio-Guided Isolation of Two New Hypoglycemic Triterpenoid Saponins from Polygonum capitatum.

PURPOSE: Diabetes is a common disease caused by a combination of genetic and environmental factors, which was the top three diseases threatening human health. Therefore, it is necessary to seek more efficient hypoglycemic drugs. The main objective of this study was to investigate the potential hypoglycemic effects of compounds from Polygonum capitatum. MATERIALS AND METHODS: Our experiments were divided into three steps: (1) α-amylase test and oral starch tolerance test (OSTT) for screening the biological extract part of P. capitatum; (2) chemical isolation and identification using various separation techniques, and spectrum methods; and (3) evaluation of α-amylase inhibitory activity of isolates and in silico analysis for mechanism investigation. RESULTS: The n-butanol fractioned part of P. capitatum was confirmed to be the biological part according to α-amylase test. Then, two new triterpenoid saponins were isolated from the n-butanol part, which were also the first isolated triterpenoid saponins from P. capitatum. The activities of compounds 1 and 2 against α-amylase were 51.9±2.8% and 38.1±2.2%, respectively, which was consistent with the molecular docking analysis. In which, 1 and 2 showed the binding affinity energy for α-amylase was -9.4 kcal/mol and -7.8 kcal/mol, respectively. CONCLUSION: Two new triterpenoid saponins were firstly isolated from P. capitatum, and displays potency as a hypoglycemic agent through blocking α-amylase.

[Historical evolution of Salviae Miltiorrhizae Radix et Rhizoma processing methods].

China has a long history of Salviae Miltiorrhizae Radix et Rhizoma processing with multiple methods available. The pre-sent study collated and summarized the Salviae Miltiorrhizae Radix et Rhizoma processing methods recorded in 23 related herbal medicine books, all editions of Chinese Pharmacopoeia, the 1988 edition of National Regulations for Processing of Chinese Medicine, and 20 current local processing specifications and standards. The results demonstrated various processing methods of Salviae Miltiorrhizae Radix et Rhizoma, such as removing residual part of stem, plantlet, or soil, smashing, filing, cutting, decocting, washing with wine, soaking in wine, and stir-frying with wine or blood from pig heart, while raw and wine-processed products are mainly used in modern times. Due to the lack of unified standards, the phenomena of multiple methods adopted in one place and different methods in different places have led to uneven quality of Salviae Miltiorrhizae Radix et Rhizoma pieces, even affecting the safety and effectiveness of its clinical medication. This study is expected to provide a reference for the development of Salviae Miltiorrhizae Radix et Rhizoma processing and its rational medication.

Selection of appropriate post-harvest processing methods based on the metabolomics analysis of Salvia miltiorrhiza Bunge.

Post-harvest processing is a leading cause of metabolic changes and quality loss in food products. An untargeted metabolomics approach based on UHPLC-QTOF-MS was conducted to explain metabolic changes during post-harvest processing of Salvia miltiorrhiza. A rapid identification method was established for comprehensive characterization of 56 phenolic acids and 45 tanshinones. Enzymatic browning was found to be the primary factor impacting the metabolic profile. A decreasing in free phenolic acids along with increasing in bound polyphenols was observed correlated with the deepening of browning degree. The various substructures of bound polyphenols were explored to interpret the composition of browning-associated products. It has also been found that the steaming process and control of the moisture content during slicing can effectively reduce the influence of enzymatic browning. This metabolomics study will contribute to select the optimal post-harvest processing methods for S. miltiorrhiza and provide information for post-harvest processing of similar products.

Folic Acid and Poly(ethylene glycol) Decorated Paclitaxel Nanocrystals Exhibit Enhanced Stability and Breast Cancer-Targeting Capability.

In part because of their high drug loading, nanocrystals (NCs) have seen extensive use in drug delivery, particularly for insoluble or poorly soluble drugs. It remains a challenge, however, to prepare stable nanocrystals with tumor-targeting capability. Here, we designed a novel preparation of stable paclitaxel (PTX) nanocrystals with efficient active tumor-targeting properties. PTX NC was prepared using a bottom-up method and modified with both poly(ethylene glycol) (PEG) and folic acid (FA) derivatives using film hydration. The resulting PTX NC@lipid-PEG-FA had a rodlike shape, with hydrodynamic diameters and drug loading values of 201.90 ± 2.92 nm and 31.07 ± 3.41%, respectively. The size of the PTX NC@lipid-PEG-FA was unchanged after 168 h in the presence of plasma, whereas nonmodified paclitaxel nanocrystals (PTX NC) exceeded 600 nm within 12 h under the same conditions. Cellular uptake and cellular growth inhibition experiments in 4T1 breast cancer cells showed the superiority of PTX NC@lipid-PEG-FA over PTX NC or PEGylated paclitaxel nanocrystals without FA modification (PTX NC@lipid-PEG). A pharmacokinetic evaluation in rats revealed that PTX NC@lipid-PEG-FA significantly prolonged the circulation of PTX in the bloodstream, in comparison with PTX NC or Taxol. Tissue distribution and in vivo antitumor studies in 4T1 orthotopic breast cancer-bearing nude mice showed that PTX NC@lipid-PEG-FA significantly increased the intratumor accumulation of PTX and efficiently inhibited tumor growth, in comparison with PTX NC@lipid-PEG, PTX NC, or Taxol. In summary, PTX NC@lipid-PEG-FA showed good potential for breast cancer-targeted delivery for insoluble therapeutics.

Two neolignans from Penthorum Chinense and their antiproliferative activities.

Chemical investigation of Penthorum chinense resulted in the isolation of two neolignans (1 and 2) together with two known compounds (3 and 4). The structures of compounds 1 and 2 were determined by interpretation of spectroscopic data, and absolute configurations were made based on electronic circular dichroism (ECD). All compounds were evaluated for their antiproliferative activity on hepatic stellate T6 cells (HSC-T6 cells), and 1 and 2 showed moderate activity with IC50 values of 15.3 and 10.1 µM, respectively.

High-Pressure Band-Gap Engineering and Metallization in the Perovskite Derivative Cs3 Sb2 I9.

Among photovoltaic materials, the antimony-based, perovskite-like structure Cs3 Sb2 I9 stands out owing to its low toxicity and air stability. Here, changes in the optoelectronic properties and crystal structure of the lead-free perovskite derivative Cs3 Sb2 I9 are reported, caused by pressure-induced lattice compression. At 20.0 GPa, Cs3 Sb2 I9 with a wide band gap (2.34 eV) successfully broke through the Shockley-Queisser limit (1.34 eV), accompanied by clear piezochromism from orange-yellow to opaque black. Additionally, Cs3 Sb2 I9 experienced completely reversible amorphization at 20.0 GPa. These optical changes could be attributed to atomic-orbital overlap enhancement caused by contraction of the Sb-I bond length and diminution of the Sb-I bond angle. In addition, Cs3 Sb2 I9 underwent a transition from semiconductor to conductor upon compression and obtained metallic properties at 44.3 GPa, indicating new electronic properties. The obtained results may further broaden the research prospects of halide perovskite materials in the field of photovoltaics.

Temporal dynamics of bacterioplankton communities in response to excessive nitrate loading in oligotrophic coastal water.

Coastal ecosystems are receiving elevated loads of nitrogen (N) from anthropogenic sources. Understanding how excessive N loading affects bacterioplankton communities is critical to predict the biodiversity of marine ecosystems under conditions of eutrophic disturbance. In this study, oligotrophic coastal water microcosms were perturbed with nitrate in two loading modes: 1) one-off loading at the beginning of the incubation period; and 2) periodic loading every two days for 16days. Turnover in the bacterioplankton community was investigated by 16S rDNA gene amplicon sequencing. The alpha diversity of the bacterioplankton community showed great temporal variability and similar responses to the different treatments. Bacterioplankton community composition was influenced remarkably by time and N loading mode. The effects of N loading on bacterioplankton community structure showed obvious temporal variation, probably because of the great temporal variation in environmental parameters. This study provides insights into the effects of N pollution in anthropogenically perturbed marine environments.

[Expression of inhibin B betaB subunits in the testicular tissues of azoospermia patients with different pathological alterations].

OBJECTIVE: To investigate the expression of inhibin B betaB subunits in human testicular tissues. METHODS: Eighty-three cases of the azoospermia underwent testicular biopsy. In accordance with the pathological alterations of spermatogenesis, the samples were divided into four groups: Sertoli-cell-only syndrome (n = 21); hypospermatogenesis (n = 20), maturation arrest (n = 24) and almost normal spermatogenesis (n = 18). Immunohistochemical staining for inhibin B betaB subunits was conducted on the paraffin-embedded sections of different spermatogenesis to localize inhibin B betaB subunits in the seminiferous tubules. RESULTS: Immunohistochemically, positive products of inhibin B betaB subunits were found in both the seminiferous tubules and interstitial tissues of the testis as brown or yellow particles in the cytoplasm. Leydig cells and early intermediate spermatogenic cells showed a very strong positivity; Sertoli cells in the seminiferous tubules were mostly positive; peritubular myoid cells showed a weak positive staining; but no positive expression of inhibin B betaB subunits was found in late spermatids and mature sperm. CONCLUSION: Inhibin B may be produced by both Sertoli cells and early spermatogenic cells in the seminiferous tubules.

[Relationship between pathological alterations of spermatogenic impairment and serum inhibin B concentration in patients with azoospermia].

OBJECTIVE: To investigate the relationship between pathological alterations of spermatogenic impairment in seminiferous tubules and serum inhibin B concentration in patients with azoospermia and to verify the significance of INH B in evaluating spermatogenesis. METHODS: Eighty-three cases of azoospermia underwent testicular biopsy for the purpose of diagnosis. In accordance with the pathological alterations of spermatogenesis in seminiferous tubules, the samples were divided into four groups: Sertoli cell-only syndrome (n = 21); hypospermatogenesis (n = 20); maturation arrest (n = 24) and almost normal spermatogenesis (n = 18). Serum INHB and FSH, LH, T concentrations were tested before testicular biopsy for each patient respectively. RESULTS: The INHB levels were (20. 85 +/- 18.78) pg/ml, (67.25 +/- 40.98) pg/ml, (73.63 +/- 25.54) pg/ml and (149.48 +/- 27.92) pg/ml in the above four groups, respectively. There was no significant statistical difference in the level of serum INH B between maturation arrest and hypospermatogenesis groups (P > 0.05), and there was a very significant difference in almost normal spermatogenesis group and the other three groups, respectively (P < 0.001). There was no significant difference in the concentration of serum FSH when maturation arrest group compared with spermatogenesis group (P > 0.05), whereas between the other two groups and between each of them and maturation arrest or almost normal spermatogenesis there was a very significant difference in the level of serum FSH (P < 0.05); The concentrations of LH and T were not significantly different among the four groups (P > 0.05). CONCLUSION: Serum INHB concentration was decreased when spermatogenesis got impaired. It dropped the most markedly in Sertoli cell-only syndrome group. INH B reflects directly the spermatogenic function in seminiferous tubules of the testis. Therefore, it could be considered valuable for spermatogenesis and potential fertility in patients with azoospermia.

[Contrasting experiment of two types of MSW aerobic bioreactor landfill].

Bioreactor landfill is an emerging landfilling method, which represents the newest developing aspect of Municipal Solid Wastes (MSW) treatment. On basis of analyzing the merits and defects of present bioreactor landfilling methods, the paper improves these methods and combines organically aeration and leachate recirculation into a new reactor (called reactor A), which is contrasted with bare aerobic landfill (called reactor B). During the course of experiment, NH3, CH4, CO2, pH, temperature and electric conductivity in the two bioreactors were controlled and detected, meanwhile, COD, Fe3+, NH4(+) in the leachate were detected and analyzed. The paper researches on the wastes degradation and the COD, Fe3+ and NH4(+) removal of the two bioreactors, probes into the mechanics of wastes and leachate degradation. Finally the paper draws a conclusion that the effect of degrading wastes and leachate of bioreactor A is better than that of bioreactor B.