Asiaticoside alleviates lipopolysaccharide-induced acute lung injury by blocking Sema4D/CD72 and inhibiting mitochondrial dysfunction in RAW264.7 cell and mice.

Acute lung injury (ALI) is a common disease with complex pathogenesis. However, the treatment is mainly symptomatic with limited clinical options. Asiaticoside (AS), a Chinese herbal extract, has protective effects against LPS-induced ALI in mice and inhibits nitric oxide and prostaglandin E2 synthesis; however, the specific mechanism of AS in the prevention and treatment of LPS-induced ALI needs further study. Sema4D/CD72 pathway, mitochondrial dysfunction, and miRNA-21 are closely associated with inflammation. Therefore, the present study aimed to explore whether AS exerts its therapeutic effect on ALI by influencing Sema4D/CD72 pathway and mitochondrial dysfunction, restoring the balance of inflammatory factors, and influencing miRNA-21 expression. Cell and animal experiments were performed to investigate the effect of AS on ALI. Lipopolysaccharide (LPS) was used to establish the ALI model. CCK8 and flow cytometry were used to detect the cell viability and apoptosis rate. HE staining and wet-to-dry weight ratio (W/D) of lung tissue were determined. The expressions of Sema4D, CD72, NF-κB p65, Bax, Bcl2, and caspase 3 in RAW264.7 cells and lung tissues were detected by western blot, and the levels of IL-10 and IL-1ß induced by LPS in supernatant of RAW264.7 cells and BALF were measured by ELISA. And the expression of miRNA-21 in cells and lung tissues was detected by fluorescence quantitative PCR. The result shows that AS treatment suppressed LPS-induced cell damage and lung injury in mice. AS treatment could alleviate the pathological changes such as inflammatory infiltration and histopathological changes in the lungs caused by LPS, and reduce the ratio of W/D. AS significantly alleviated the decrease of mitochondrial membrane potential induced by LPS, inhibited the increase of ROS production, and reduced the expression of mitochondrial fission proteins Drp1 and Fis1. The high-dose AS group significantly downregulated the expression of Sema4D, CD72, phosphorylated NF-κB p65, and apoptosis-related proteins, decreased the pro-inflammatory factor IL-1ß, and enhanced the level of anti-inflammatory factor IL-10. In addition, AS promoted miRNA-21 expression. These effects inhibited apoptosis and restored the balance between anti- and pro-inflammatory factors. This represents the inaugural report elucidating the mechanism by which AS inhibits the Sema4D/CD72 signaling pathway. These findings offer novel insights into the potential application of AS in both preventing and treating ALI.

Eumelanin-like Poly(levodopa) Nanoscavengers for Inflammation Disease Therapy.

In the current years, polydopamine nanoparticles (PDA NPs) have been extensively investigated as an eumelanin mimic. However, unlike natural eumelanin, PDA NPs contain no 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-derived units and may be limited in certain intrinsic properties; superior eumelanin-like nanomaterials are still actively being sought. Levodopa (l-DOPA) is a natural eumelanin precursor and expected to convert into DHICA and further remain within the final product through covalent or physical interactions. Herein, poly(levodopa) nanoparticles [P(l-DOPA) NPs] were synthesized with the assistance of zinc oxide as a supplement to synthetic eumelanin. This study found that P(l-DOPA) NPs had ∼90% DHICA-derived subunits on their surface and exhibited superior antioxidant activity compared to PDA NPs due to their looser polymeric microstructure. Benefitting from a stronger ROS scavenging ability, P(l-DOPA) NPs outperformed PDA NPs in treating cellular oxidative stress and acute inflammation. This research opens up new possibilities for the development and application of novel melanin-like materials.

Dihydroquercetin improves experimental acute liver failure by targeting ferroptosis and mitochondria-mediated apoptosis through the SIRT1/p53 axis.

BACKGROUND: Ferroptosis and mitochondria-mediated apoptosis are both involved in the pathogenesis of acute liver failure (ALF). Ferroptosis-produced reactive oxygen species (ROS) trigger the chain oxidation of polyunsaturated phospholipids and promote mitochondrial apoptosis. Dihydroquercetin (DHQ) also plays an important protective role against liver injury. PURPOSE: Here, we aimed to investigate the protective effects of DHQ on ALF. We also explored the underlying mechanism. METHODS: We established a Lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced ALF mouse model and tumor necrosis factor-α (TNF-α)/D-Gal-induced ALF LO2 cell model. 2',7'-Dichlorofluorescein diacetate (DCFH-DA) and Dihydroethidium (DHE) were used to detect total ROS levels. Lipid ROS was assessed using C11-BODIPY flow cytometry. Lipid peroxidative products levels were detected using MDA ELISA assay and 4-hydroxynonenal (4-HNE) immunohistochemistry. QRT-PCR and western blots were used to test mRNA and protein expression levels, respectively. Cell viability was evaluated with CCK8 assay, and apoptosis was analyzed using flow cytometry. RESULTS: DHQ treatment improved LPS/D-Gal-induced ALF, as well as TNF-α/D-Gal-induced reductions in LO2 viability and increased sirtuin 1 (SIRT1) expression. DHQ pretreatment also reduced the accumulation of ROS, reduced lipid peroxidation, elevated mitochondrial membrane potentials (ΔΨm), and decreased liver cell apoptosis both in vivo and in vitro. Additionally, the knockdown of SIRT1 and p53 activator (Tenovin-6) treatment reversed DHQ's inhibitory effects on ferroptosis and mitochondria-mediated apoptosis in vitro. DHQ enhanced p53 deacetylation by both up-regulating SIRT1 expression and directly bonding to SIRT1. We also found that Tenovin-6's stimulatory effects on ferroptosis and mitochondria-mediated apoptosis in the DHQ-treated LO2 ALF cell model were partially attenuated by overexpression of solute carrier family 7member 11 (SLC7A11), as well as by apoptotic protease activating factor 1 (Apaf-1) knockdown. CONCLUSION: Our results suggest that DHQ alleviated ALF by inhibiting both ferroptosis and mitochondria-mediated apoptosis by regulating the SIRT1/p53 axis. Thus, DHQ may serve as a novel therapy for ALF.

Sevoflurane causes cognitive impairment by inducing iron deficiency and inhibiting the proliferation of neural precursor cells in infant mice.

AIMS: Numerous studies on animals have shown that exposure to general anesthetics in infant stage may cause neurocognitive impairment. However, the exact mechanism is not clear. The dysfunction of iron metabolism can cause neurodevelopmental disorders. Therefore, we investigated the effect of iron metabolism disorder induced by sevoflurane (Sev) on cognitive function and the proliferation of neural precursor cells (NPCs) and neural stem cells (NSCs) in infant mice. METHODS: C57BL/6 mice of postnatal day 14 and neural stem cells NE4C were treated with 2% Sev for 6 h. We used the Morris water maze (MWM) to test the cognitive function of infant mice. The proliferation of NPCs was measured using bromodeoxyuridine (BrdU) label and their markers Ki67 and Pax6 in infant brain tissues 12 h after anesthesia. Meanwhile, we used immunohistochemical stain, immunofluorescence assay, western blot, and flow cytometer to evaluate the myelinogenesis, iron levels, and cell proliferation in cortex and hippocampus or in NE4C cells. RESULTS: The results showed that Sev significantly caused cognitive deficiency in infant mice. Further, we found that Sev inhibited oligodendrocytes proliferation and myelinogenesis by decreasing MBP and CC-1 expression and iron levels. Meanwhile, Sev also induced the iron deficiency in neurons and NSCs by downregulating FtH and FtL expression and upregulating the TfR1 expression in the cortex and hippocampus, which dramatically suppressed the proliferation of NSCs and NPCs as indicated by decreasing the colocalization of Pax6+ and BrdU+ cells, and caused the decrease in the number of neurons. Interestingly, iron supplementation before anesthesia significantly improved iron deficiency in cortex and hippocampus and cognitive deficiency induced by Sev in infant mice. Iron therapy inhibited the decrease of MBP expression, iron levels in neurons and oligodendrocytes, and DNA synthesis of Pax6+ cells in hippocampus induced by Sev. Meanwhile, the number of neurons was partially recovered in hippocampus. CONCLUSION: The results from the present study demonstrated that Sev-induced iron deficiency might be a new mechanism of cognitive impairment caused by inhaled anesthetics in infant mice. Iron supplementation before anesthesia is an effective strategy to prevent cognitive impairment caused by Sev in infants.

Online-merge-offline (OMO)-based music therapy for asthmatic children during the COVID-19 pandemic in China.

The purpose of this study is to evaluate online-merge-offline (OMO)-based music therapy (MT) as a complementary option for asthma management in pediatric patients. A total of 86 children diagnosed with mild asthma were enrolled and treated with the same drug therapy. They were assigned into three groups: Music I group (standard medical care plus a single individualized MT session along with singing training and breathing exercise), Music II group (similar as Music I as well as further wind instrument playing), and Control group (standard medical care). Primary endpoints included pulmonary function tests FEV1, FVC, FEV1/FVC, MMEF 75/25, and PEF, c-ACT, PAQLQ, and PACQLQ. After 6 months of continuous intervention of MT, significant differences in FEV1, FVC, MMEF75/25, PEF, c-ACT score, PAQLQ, PACQLQ (p < 0.001), and FEV1/FVC (p < 0.05) were observed among Music I, Music II, and Control groups. Besides, FEV1, FVC, FEV1/FVC, MMEF75/25, and PEF showed positive trends in Music I and Music II groups compared to those in Control group (p < 0.05). The c-ACT score of children was significantly increased in Music I (p < 0.001) and II (p < 0.001) groups in contrast with Control group. Children in Music I and II groups had better quality of life than those in Control group (PAQLQ, p < 0.001), and the parents in Music I and II groups also showed better quality of life than those in Control group (PACQLQ, p < 0.001).     Conclusion: As a child-friendly, low-risk, and convenient intervention, the OMO-based MT has a positive impact on pediatric asthma management during the COVID-19 pandemic. What is Known: • A few findings proved the positive effect of MT on pediatric asthma. What is New: • Our study further proving the validation and effectiveness of MT with OMO-based model on pediatric asthma, wind instrument playing has a greater impact on pediatric asthma control via small airways and might be recommended to mix to singing and breathing to improve effectiveness of MT for asthmatic children.

Music Therapy in Pediatric Asthma: A Short Review.

Music therapy (MT) is a common modality that performs a complementary and integrative role along with standard treatments for many pediatric diseases. This article briefly reviewed the effects of MT on children aged 5-11 years old and adolescents with asthma from previous studies, specified its functional target towards asthma symptoms, and sorted out the design and investigation of selected research. Medline/PubMed, Embase, SportDis-cus, Cochrane Library, Teacher Reference Centre, Web of Science, Academic Search Complete, PsycARTICLES, and Scopus were queried for experimental and observational studies published between 1990 and 2021. Then, researchers showed that MT lessened patients' asthma symptoms, improved medication compliance, pulmonary function, and quality of life, and helped children and their parents manage anxiety and depression. This article may serve as a reference for clinical research for pediatric asthma therapies and lay the foundation for future research on MT and its clinical practice.

The application of traditional Chinese medicine nursing combined with the health education standard path in acute myeloid leukaemia.

Objective: The standard path of health education is a standardised health education method formulated according to the characteristics of the disease in question. This study aimed to explore the effect of traditional Chinese medicine (TCM) nursing combined with the health education standard path in terms of acute myeloid leukaemia (AML). Methods: Sixty patients with AML at Shijiazhuang Ping'an Hospital were recruited and divided into the control group (n = 30) and the intervention group (n = 30). Both groups received the same chemotherapy treatment, while the control group received routine nursing and the intervention group received a combined TCM-health education standard path intervention. The scores for the self-rating anxiety scale (SAS), Spitzer quality of life index (QLI), self-rating depression scale (SDS), awareness of TCM health education standard path content and nursing satisfaction were then compared. Results: The SAS and SDS scores of the patients decreased following the intervention, while the QLI score increased, with the intervention group significantly improved compared to the control group (P < 0.05). The awareness of TCM health education standard path content was significantly higher in the intervention group than in the control group (P < 0.05), and the nursing satisfaction was also higher in the former than in the latter (P < 0.05). Furthermore, the hospitalisation cost and length of stay were lower in the intervention group than in the control group (P < 0.05). There were no statistical differences in the median survival time between the intervention group and the control group (P > 0.05). Conclusion: The application of TCM combined with the health education standard path has an effect in terms of reducing patients' anxiety and depression, improving their awareness of health education content and enhancing their nursing satisfaction.

Sevoflurane inhibited reproductive function in male mice by reducing oxidative phosphorylation through inducing iron deficiency.

Sevoflurane (Sev) is one of the commonly used inhalation anesthetic chemicals in clinics. It has great impact on spermatogenesis and fertilization in male animals. The underlying mechanism remains largely unexplored. Based on our previous research, we hypothesized that Sev induced iron metabolism disturbance in the testis and epididymis and inhibited the spermatogenesis. In this study, two-month-old C57BL/6 male mice were treated with 3% Sev for 6 h, and their fertility (including sperm concentration, sperm mobility, and the number of offspring) was evaluated. Mice testis, epididymis, and sperm were harvested and subjected to Western blot analysis and immunofluorescence analysis. Iron levels were reflected by the gene expression of iron metabolism-related proteins (including ferritin, TfR1, and FpN1) and ICP-MS and Perl's iron staining. Electron transport and oxidative phosphorylation levels were measured by Oxygraph-2k and ATP contents. The activity of ribonucleotide reductase was evaluated by assay kit. DNA synthesis status in testis and/or epididymis was marked with BrdU. Cell proliferation was evaluated by double immunofluorescence staining of specific protein marker expression. Our results revealed that the mice exposed to Sev showed damaged testicular and epididymis structure and significantly reduced the sperm concentration, sperm motility, and fertility. Sev decreases the iron levels through down-regulating the expression of H-ferritin, L-ferritin, and FpN1, and up-regulating the expression of TfR1 in the testis and epididymis. Iron levels also significantly reduced in germ cells which decrease the number of germ cells, including sperm, Sertoli cells, and primary spermatocyte. Iron deficiency not only decreases electron transport, oxidative phosphorylation level, and ATP production but also suppresses the activity of ribonucleotide reductase and the expression of Ki67, DDX4, GATA1, and SCP3, indicating that Sev affects the spermatogenesis and development. Meanwhile, Sev impaired the blood-testis barrier by decreasing the ZO1 expression in the testis and epididymis. The damage effect induced by Sev can be significantly ameliorated by iron supplementation. In conclusion, our study illustrates a new mechanism by which Sev inhibits spermatogenesis and fertility through an oxidative phosphorylation pathway due to iron deficiency of epididymis and testis or sperm. Furthermore, the damaging effects could be ameliorated by iron supplementation.

Overexpression of LaGRAS enhances phosphorus acquisition via increased root growth of phosphorus-deficient white lupin.

The GRAS transcription factors play an indispensable role in plant growth and responses to environmental stresses. The GRAS gene family has extensively been explored in various plant species; however, the comprehensive investigation of GRAS genes in white lupin remains insufficient. In this study, bioinformatics analysis of white lupin genome revealed 51 LaGRAS genes distributed into 10 distinct phylogenetic clades. Gene structure analyses revealed that LaGRAS proteins were considerably conserved among the same subfamilies. Notably, 25 segmental duplications and a single tandem duplication showed that segmental duplication was the major driving force for the expansion of GRAS genes in white lupin. Moreover, LaGRAS genes exhibited preferential expression in young cluster root and mature cluster roots and may play key roles in nutrient acquisition, particularly phosphorus (P). To validate this, RT-qPCR analysis of white lupin plants grown under +P (normal P) and -P (P deficiency) conditions elucidated significant differences in the transcript level of GRAS genes. Among them, LaGRAS38 and LaGRAS39 were identified as potential candidates with induced expression in MCR under -P. Additionally, white lupin transgenic hairy root overexpressing OE-LaGRAS38 and OE-LaGRAS39 showed increased root growth, and P concentration in root and leaf compared to those with empty vector control, suggesting their role in P acquisition. We believe this comprehensive analysis of GRAS members in white lupin is a first step in exploring their role in the regulation of root growth, tissue development, and ultimately improving P use efficiency in legume crops under natural environments.

Engineering Streptomyces albulus to enhance ε-poly-L-lysine production by introducing a polyphosphate kinase-mediated ATP regeneration system.

BACKGROUND: ε-Poly-L-lysine (ε-PL) is a natural and safe food preservative that is mainly produced by filamentous and aerobic bacteria Streptomyces albulus. During ε-PL biosynthesis, a large amount of ATP is used for the polymerization of L-lysine. A shortage of intracellular ATP is one of the major factors limiting the increase in ε-PL production. In previous studies, researchers have mainly tried to increase the oxygen supply to enhance intracellular ATP levels to improve ε-PL production, which can be achieved through the use of two-stage dissolved oxygen control, oxygen carriers, heterologous expression of hemoglobin, and supplementation with auxiliary energy substrates. However, the enhancement of the intracellular ATP supply by constructing an ATP regeneration system has not yet been considered. RESULTS: In this study, a polyphosphate kinase (PPK)-mediated ATP regeneration system was developed and introduced into S. albulus to successfully improve ε-PL production. First, polyP:AMP phosphotransferase (PAP) from Acinetobacter johnsonii was selected for catalyzing the conversion of AMP into ADP through an in vivo test. Moreover, three PPKs from different microbes were compared by in vitro and in vivo studies with respect to catalytic activity and polyphosphate (polyP) preference, and PPK2Bcg from Corynebacterium glutamicum was used for catalyzing the conversion of ADP into ATP. As a result, a recombinant strain PL05 carrying coexpressed pap and ppk2Bcg for catalyzing the conversion of AMP into ATP was constructed. ε-PL production of 2.34 g/L was achieved in shake-flask fermentation, which was an increase of 21.24% compared with S. albulus WG608; intracellular ATP was also increased by 71.56%. In addition, we attempted to develop a dynamic ATP regulation route, but the result was not as expected. Finally, the conditions of polyP6 addition were optimized in batch and fed-batch fermentations, and the maximum ε-PL production of strain PL05 in a 5-L fermenter was 59.25 g/L by fed-batch fermentation, which is the highest ε-PL production reported in genetically engineered strains. CONCLUSIONS: In this study, we proposed and developed a PPK-mediated ATP regeneration system in S. albulus for the first time and significantly enhanced ε-PL production. The study provides an efficient approach to improve the production of not only ε-PL but also other ATP-driven metabolites.

Twelve-component pharmacokinetic study of rat plasma after oral administration of You-Gui-Wan in osteoporosis rats with kidney-yin deficiency and kidney-yang deficiency.

You-Gui-Wan is a widely used traditional Chinese medicine preparation for the treatment of osteoporosis with kidney-yang deficiency, and is composed of both yang-invigorating and kidney-tonifying herbs, and yin-nourishing and kidney essence-replenishing herbs. Considering that the pharmacokinetics of drugs might differ in different pathological conditions, it is necessary to study the pharmacokinetic characteristics of You-Gui-Wan under different osteoporotic conditions. In this study, the pharmacokinetic behaviors of You-Gui-Wan in osteoporosis rats with kidney-yin and kidney-yang deficiency were compared. The results showed that the absorption, metabolism, and disposition of You-Gui-Wan varied widely in animals with different types of osteoporosis. The active components belonging to the yang-invigorating herbs, such as aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypacoitine, benzoylmesaconine, chlorogenic acid and pinoresinol diglucoside, had a higher uptake and slower elimination in osteoporosis rats with kidney-yang deficiency, which corresponds to the opinion that You-Gui-Wan is used to treat kidney-yang deficiency syndrome, and indicates the scientific nature of Bian-Zheng-Lun-Zhi.

Comparative Pharmacokinetic Study of 5 Active Ingredients after Oral Administration of Zuogui Pill in Osteoporotic Rats with Different Syndrome Types.

Zuogui Pill is a kidney-yin-tonifying formula in traditional Chinese medicine that is widely used to manage osteoporosis with kidney-yin-deficiency in China. Herein, an efficient and accurate high-performance liquid chromatography-tandem mass spectrometry method was developed to determine the concentrations of 5 bioactive compounds in rat plasma following oral administration of Zuogui Pill. Because drug absorption and distribution differ under physiological and pathological conditions, the established method was used to quantify blood components and dynamic change in osteoporotic rats with different syndrome types. Moreover, integrated pharmacokinetic study was conducted to describe the overall pharmacokinetic characteristics of traditional Chinese medicine. The results showed that the absorption, distribution, and metabolism of Zuogui Pill varied widely under different states. The bioavailability of most active components showed significant advantages in osteoporotic rats with kidney-yin-deficiency, which corresponds to the opinion that Zuogui Pill has the effect of nourishing kidney-yin. It is hoped that this finding could interpret the pharmacodynamic substances and mechanism of Zuogui Pill in the treatment of osteoporosis with kidney-yin-deficiency.

[Effects of Sediment Dredging on the Reduction in Sediment Internal Loading of Lake Taihu and the Self-recovery Ability of Benthic Organism].

Sediment dredging has a great effect on the control of lake internal loading and is one of the important methods for lake internal loading management. In this study, the dredged area of Taihu Lake was used as the main object. An estimation of the reduction in whole lake internal loading of Taihu Lake in decade years was carried out. At the same time, we evaluated the effect of sediment dredging on the control of internal loading in the northern area of Taihu Lake (Zhushan Bay and Meiliang Bay). The results indicated that a total of 42 million cubes of sediment was dredged from Taihu Lake, and the total nitrogen, total phosphorus, and organic matter in the dredged sediment was estimated to be approximately 6.26×104 tons, 1.83×104 tons, and 11.7×105 tons, respectively. This was roughly equal to the 20 years of external loading pollution accumulated in Taihu Lake. From a long-term perspective, sediment dredging could effectively increase the water quality of Meiliang Bay within five years and that where the external loading has been controlled effectively. However, the water quality of Meiliang Bay subsequently rebounded, but dredging still reduced the nitrogen and phosphorus content in surface sediment. On the contrary, dredging could not effectively control the internal loading of Zhushan Bay, which still had a large input of external loading. The amount of sediment internal loading recovered to the original level of the pre-dredging period. In a six-year-long period of continuous monitoring of the benthic organism community of Zhushan Bay, the results indicated that sediment dredging could cause negative effects on sediment dredging initially, but the density and biomass of the benthic organisms in the dredged area had later been recovered to the un-dredged level. There was no difference between the dredged and un-dredged areas with regard to the diversity indices of benthic organisms. The results of this study indicated that sediment dredging can effectively control the lake internal loading. However, the maintenance period of dredging effects was related closely to the input intensity of the external loading. In addition, sediment dredging did not have a large influence on the benthic organism community and could recover to the original level depending on self-recovery.

Solid SiO2-Sealed Mesoporous Silica for Synergistically Combined Use of Inorganic and Organic Filters to Achieve Safe and Effective Skin Protection from All-Band UV Radiation.

To effectively shield the full band of ultraviolet (UV) radiation and provide desirable protection, the combination of inorganic and organic filters was often used to protect human skin from the serious harm of UV exposure. However, the incompatibility of different filters and their mutual negative effect limit the production of multifilter sunscreen. In addition, the hazard of reactive oxygen species (ROS) produced by inorganic filters after UV exposure and the skin permeability of organic filters remain unresolved problems. In this study, titanium dioxide (TiO2) and diethylamino hydroxybenzoyl hexyl benzoate (DHHB), two kinds of common filters with complementary UV shielding range, were first encapsulated into large mesoporous silica nanoparticles (MSN, ∼300 nm) to obtain MSN-TiO2 and MSN-DHHB. Also, a SiO2 coating was then made to seal and stabilize the MSN-TiO2 and MSN-DHHB. The structure, UV screen function, and safety of the SiO2-coated filters, MSN-TiO2@SiO2 and MSN-DHHB@SiO2, were evaluated. The good mechanical stability exhibited by the solid SiO2 layer prevented the release and skin penetration of the sealed DHHB and the photocatalysis of TiO2. Furthermore, the combination of MSN-TiO2@SiO2 and MSN-DHHB@SiO2 in sunscreen cream showed excellent UV shielding performance on covering the whole UV radiation range without mutual interference. Therefore, coating SiO2 over MSN is a feasible strategy for entrapping various filters to improve their photostability, preventing skin penetration and ROS generation, and enhancing their compatibility with different sunscreen formulations.

Comparative pharmacokinetic study of nine bioactive components in osteoarthritis rat plasma using ultra-performance liquid chromatography-tandem mass spectrometry after single and combined oral administration of Epimedii Folium and Chuanxiong Rhizoma extracts.

The herb pair Epimedii Folium-Chuanxiong Rhizoma (EF-CR), derived from the classical traditional Chinese medicine 'Xian Ling Pi San', has a distinctive compatibility therapeutic profile and is clinically safe and effective. This study aimed to investigate and compare the pharmacokinetic characteristics of nine analytes in osteoarthritis (OA) rat plasma after the oral administration of EF, CR or a combination of these two herbs. We developed an ultra-performance liquid chromatography method coupled with quadrupole linear ion-trap mass spectrometry to simultaneously quantify and assess the pharmacokinetics of icariin, epimedin A, epimedin B, epimedin C, icariside I, icariside II, ferulic acid, ligustilide and senkyunolide A of the EF-CR pair in the plasma of osteoarthritic rats. The pharmacokinetic parameters showed that the absorption of multiple components was significantly enhanced and residence time was prolonged in the EF-CR group (P < 0.05) compared to the single-herb group. These parameters revealed that the combination of EF and CR exhibited synergistic effects of the nine bioactive components, suggesting the potential application of the EF-CR combination for the treatment of OA.

Key Targets and Molecular Mechanisms of Active Volatile Components of Rabdosia rubescens in Gastric Cancer Cells.

OBJECTIVE: To examine the effect and mechanism of volatile components of Rabdosia rubescens on gastric cancer. METHODS: Gas chromatography-mass spectrometry was used to detect and identify the volatile components of R. rubescens. The network pharmacology method was used to analyze the targets of volatile components of R. rubescens in gastric cancer and to reveal their molecular mechanisms. The effects of volatile components of R. rubescens on gastric cancer cells were verified by biological experiments. RESULTS: Thirteen volatile components of R. rubescens were selected as pharmacologically active components. The 13 active components had 83 targets in gastric cancer, and a Traditional Chinese Medicine-component-targets gastric cancer network was successfully constructed. Five core targets were obtained: TNF, IL1B, MMP9, PTGS2 and CECL8. The volatile components inhibited the proliferation of gastric cancer cells in a concentration-dependent manner and promoted the apoptosis of gastric cancer cells. The volatile components reduced the levels of TNF, IL1B, MPP9, and PTGS2 in a concentration-dependent manner. CONCLUSION: Our study demonstrates the effects of volatile components in R. rubescens on gastric cancer and provides preliminary findings on their mechanisms of action.

Root acid phosphatases and rhizobacteria synergistically enhance white lupin and rice phosphorus acquisition.

The rhizosheath is a belowground area that acts as a communication hub at the root-soil interface to promote water and nutrient acquisition. Certain crops, such as white lupin (Lupinus albus), acquire large amounts of phosphorus (P), owing partially to exudation of acid phosphatases (APases). Plant growth-promoting rhizobacteria also increase soil P availability. However, potential synergistic effects of root APases and rhizosheath-associated microbiota on P acquisition require further research. In this study, we investigated the roles of root purple APases (PAPs) and plant growth-promoting rhizobacteria in rhizosheath formation and P acquisition under conditions of soil drying (SD) and P treatment (+P: soil with P fertilizer; -P: soil without fertilizer). We expressed purple acid phosphatase12 (LaPAP12) in white lupin and rice (Oryza sativa) plants and analyzed the rhizosheath-associated microbiome. Increased or heterologous LaPAP12 expression promoted APase activity and rhizosheath formation, resulting in increased P acquisition mainly under SD-P conditions. It also increased the abundance of members of the genus Bacillus in the rhizosheath-associated microbial communities of white lupin and rice. We isolated a phosphate-solubilizing, auxin-producing Bacillus megaterium strain from the rhizosheath of white lupin and used this to inoculate white lupin and rice plants. Inoculation promoted rhizosheath formation and P acquisition, especially in plants with increased LaPAP12 expression and under SD-P conditions, suggesting a functional role of the bacteria in alleviating P deficit stress via rhizosheath formation. Together, our results suggest a synergistic enhancing effect of LaPAP12 and plant growth-promoting rhizobacteria on rhizosheath formation and P acquisition under SD-P conditions.

Global Identification of White Lupin lncRNAs Reveals Their Role in Cluster Roots under Phosphorus Deficiency.

Phosphorus (P) deficiency heterogeneously affected plant nutritional status and physiological performance, ultimately leading to a severe yield reduction. A few putative long non-coding RNAs (lncRNAs) responding to P-starvation in the model crops Arabidopsis thaliana and Oryza sativa have been characterized. White lupin (Lupinus albus) is of prime importance, and is a legume with increasing agronomic value as a protein crop as it exhibits extreme tolerance to nutrient deficiency, particularly P deficiency. Despite its adapted nature to P deficiency, nothing is known about low P-induced lncRNAs in white lupin roots. To address this issue, we identified 39,840 mRNA and 2028 lncRNAs in the eight developmental stages of white lupin root (S0-S7 and lateral root, LR) grown under P deficiency. From these 2028 lncRNAs, 1564 were intergenic and 464 natural antisense intergenic transcript (NAT) lncRNAs. We further predicted six potential targets of miRNAs with twelve lncRNAs, which may regulate P-deficiency-related processes. Moreover, the weighted gene co-expression network analysis (WGCNA) revealed seven modules that were correlated with the expression pattern of lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed 606 GO terms and 27 different pathways including signal transduction, energy synthesis, detoxification, and Pi transport. In addition, we screened 13 putative lncRNAs that showed a distinct expression pattern in each root, indicating their role in the P deficiency regulatory network. Therefore, white lupin may be a reference legume to characterize P-deficiency-responsive novel lncRNAs, which would highlight the role of lncRNAs in the regulation of plant responses to P deficiency.

Study on the Diagnostic Value of Contrast-Enhanced Ultrasound and Magnetic Resonance Imaging in Prostate Cancer.

Objective: The aim is to study the different roles of single and joint application of magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in prostate malignant tumors. Methods: 72 patients with prostate masses who underwent CEUS and MRI examination in our hospital from October 2021 and March 2022 were enrolled in this research. The differentially diagnostic roles of CEUS, MRI, and CEUS combined MRI for prostate cancer was assessed on basis of pathological findings as the reference standard. The specificity and sensitivity of the joint application for prostate malignant tumors with various prostate-specific antigen (PSA) levels were also evaluated. Results: The sensitivity of CEUS, MRI, and the joint application for prostate cancer were 72.1%, 74.4%, and 90.7%, respectively. Compared with single application, the sensitivity of CEUS combined with MRI was significantly higher. The specificity of MRI, CEUS, and the combination of the two for prostate cancer were 82.8%, 79.3%, and 89.7%, respectively, and the statistical differences for specificity were not found. The area under ROC curve (AUC) of CEUS combined with MRI in prostate malignant tumor diagnosis was obviously more than that of CEUS and MRI (P < 0.05). CEUS combined with MRI has relative high sensitivity in these patients with different levels of PSA. Conclusions: Contrast-enhanced ultrasound combined with MRI can significantly improve the sensitivity and specificity of prostate cancer diagnosis so that patients can be better diagnosed in advance.

Comparative Analysis of the Efficacy of Transurethral Bipolar Plasma Needle Electrode and Ring Electrode in the Treatment of Non-Muscle-Invasive Bladder Cancer.

Bladder cancer is the most prevalent tumor of the urinary tract, ranking seventh in males and seventeenth in women. The gold standard for the definitive diagnosis and initial treatment of non-muscle-invasive bladder cancer is transurethral resection (TUR) of the bladder tumor. The ability to accurately detect disease, typically in the presence of hematuria as well as to detect early recurrent tumors in patients with a history of NMIBC, is critical to the successful treatment of non-muscle-invasive bladder cancer (NMIBC). Unfortunately, the current biomarker landscape for NMIBC is still evolving. Cystoscopy remains the gold standard, but it can still miss 10% of tumors. As a result, physicians frequently employ additional diagnostic tools to aid in the diagnosis of bladder cancer. The efficacy of transurethral bipolar plasma needle electrodes and ring electrodes in the treatment of non-muscle-invasive bladder cancer was compared and analyzed in this study. During our study, 100 patients with non-muscle-invasive bladder cancer admitted to our hospital between June 2019 and June 2020 were randomly assigned to a control group and an observation group, with 50 cases in each group. The observation group was given a bipolar plasma needle electrode, while the control group was given a bipolar plasma ring. Patients continued to receive bladder irrigation chemotherapy as well as traditional Chinese medicine (TCM) treatment as part of our treatment plan, while the control group received only bladder irrigation chemotherapy. Clinical factors such as operational blood loss, catheter indention time, length of hospital stay, and others were compared between the two groups. When the risk grades in the two groups were compared, the observation group had fewer medium- and high-risk grades than the control group, but the control group had more low-risk grades, with statistical significance (P < 0.05).