[Off-line comprehensive two-dimensional countercurrent chromatography-liquid chromatography separation of Curcuma volatile oil].

The chemical constituents of volatile oils used in traditional Chinese medicine are highly complex. Thus, achieving the complete separation of volatile oils by one-dimensional chromatography is difficult owing to the low peak capacity of the technique. Although comprehensive two-dimensional gas chromatography provides an efficient means for separating volatile oils, it cannot be used to screen bioactive components because of its limitations. Therefore, developing a new method to separate volatile oils based on liquid chromatography is of great significance in efforts to obtain new approaches to screen bioactive components in volatile oil. The objectives of the present study are to establish an efficient method for separating the chemical constituents of Curcuma volatile oil using off-line comprehensive two-dimensional countercurrent chromatography-liquid chromatography (CCC-LC) and to investigate the two-dimensional peak capacity, orthogonality, and spatial coverage of this method. Both CCC and LC conditions were optimized. A biphasic n-hexane-methanol-water solvent system was selected via the colorimetric method, and the lower phase was used as the mobile phase in gradient-elution mode: 0-55 min, n-hexane-methanol-water (5∶2∶3 v/v/v); 55-170 min, n-hexane-methanol-water (5∶3∶2, v/v/v); 170-290 min, n-hexane-methanol-water (5∶4∶1, v/v/v). After gradient elution, elution-extrusion elution mode was applied within 290-375 min. Good resolution was achieved by the CCC separation process. The HPLC separation process was carried out with gradient elution using a mobile phase composed of acetonitrile (A)-water (B): 0-10 min, 50%A-65%A; 10-14 min, 65%A; 14-21 min, 65%A-85%A; 21-25 min, 85%A-95%A; 25-30 min, 95%A-55%A; 30-40 min, 55%A. Curcuma volatile oil was separated under the above optimized two-dimensional separation conditions, and the data obtained were drawn into a two-dimensional contour map using Matlab software. The calculated total peak capacity exceeded 954, which was 10 times more than that of one-dimensional chromatography. High orthogonality (r=0.17) and spatial coverage factor (68.1%) were also obtained. Our research provides a new methodology for separating volatile oils used in traditional Chinese medicine as well as an approach for evaluating the quality of traditional Chinese medicinal herbs using two-dimensional chromatographic fingerprints.

Revealing the metabolomics and biometrics underlying phytotoxicity mechanisms for polystyrene nanoplastics and dibutyl phthalate in dandelion (Taraxacum officinale).

Micro/nanoplastics (M/NPs) and phthalates (PAEs) are emerging pollutants. Polystyrene (PS) MPs and dibutyl phthalate (DBP) are typical MPs and PAEs in the environment. However, how dandelion plants respond to the combined contamination of MPs and PAEs remains unclear. In this study, we evaluated the individual and combined effects of PS NPs (10 mg L-1) and DBP (50 mg L-1) on dandelion (Taraxacum officinale) seedlings. The results showed that compared to control and individual-treated plants, coexposure to PS NPs and DBP significantly affected plant growth, induced oxidative stress, and altered enzymatic and nonenzymatic antioxidant levels of dandelion. Similarly, photosynthetic attributes and chlorophyll fluorescence kinetic parameters were significantly affected by coexposure. Scanning electron microscopy (SEM) results showed that PS particles had accumulated in the root cortex of the dandelion. Metabolic analysis of dandelion showed that single and combined exposures caused the plant's metabolic pathways to be profoundly reprogrammed. As a consequence, the synthesis and energy metabolism of carbohydrates, amino acids, and organic acids were affected because galactose metabolism, the citric acid cycle, and alanine, aspartic acid and glutamic acid metabolism pathways were significantly altered. These results provide a new perspective on the phytotoxicity and environmental risk assessment of MPs and PAEs in individual or coexposures.

ZmRPN1 confers quantitative variation in pollen number and boosts hybrid seed production in maize.

The number of pollen grains is a critical determinant of reproductive success in seed plants and varies among species and individuals. However, in contrast with many mutant-screening studies relevant to anther and pollen development, the natural genetic basis for variations in pollen number remains largely unexplored. To address this issue, we carried out a genome-wide association study in maize, ultimately revealing that a large presence/absence variation in the promoter region of ZmRPN1 alters its expression level and thereby contributes to pollen number variation. Molecular analyses showed that ZmRPN1 interacts with ZmMSP1, which is known as a germline cell number regulator, and facilitates ZmMSP1 localization to the plasma membrane. Importantly, ZmRPN1 dysfunction resulted in a substantial increase in pollen number, consequently boosting seed production by increasing female-male planting ratio. Together, our findings uncover a key gene controlling pollen number, and therefore, modulation of ZmRPN1 expression could be efficiently used to develop elite pollinators for modern hybrid maize breeding.

Bioinformatics Analysis of the Prognostic Significance of VPS16 in Hepatocellular Carcinoma and Its Role in Drug Screening.

Background: Vacuolar protein sorting 16 (VPS16) overexpression was recently considered related to cancer growth and drug resistance; however, little is known about whether VPS16 plays a vital role in liver hepatocellular carcinoma (LIHC). Methods: The TIMER2 online database was used to analyze the expression of VPS16 in pancancer, and the Xena Browser was used to explore the correlation between VPS16 expression level and survival time. R language was used to test the survival data of 374 LIHC cases in the TCGA database. DESeq2 was used for differentially expressed gene (DEG) analysis. The HPA database was used to verify the expression level of VPS16 in LIHC. The clusterProfiler package was used to analyze functions and related signaling pathways via GO/KEGG enrichment analysis. Drug sensitivity analysis and molecular docking technology were used to screen the most sensitive drugs targeting VPS16 molecules. Results: Pancancer analysis showed that VPS16 was highly expressed in various tumors, especially in LIHC. With the increase in the T stage and grade of LIHC, the expression level of VPS16 was also increased. The expression of VPS16 was negatively correlated with the overall survival of LIHC patients. The stage can be used as an independent prognostic factor. A total of 63 sensitive drugs were found, and 19 drugs were displaying strong molecular binding energy with VPS16. Conclusion: VPS16 may be a potential biomarker for the diagnosis and prognosis of LIHC. Drugs targeting VPS16 may be used in the treatment of LIHC in the future.

Four cases of fatal acute arsenic poisoning: histopathology, toxicology, and new trends.

Arsenic is a valuable component in tumor treatment and traditional Chinese medicine and has seen widespread use in processing, manufacturing, and agriculture. Although rare, arsenic poisoning can occur in forensic practice. Elusive pathological changes, as well as obscure clinical signs, may cause arsenic poisoning to go unrecognized. Here, we report four cases of fatal acute arsenic poisoning, with careful observation of pathological changes and collection of postmortem specimens for arsenic concentration analysis. Additionally, we reviewed six cases of fatal arsenic poisoning in the past 20 years. In the present study, microvesicular steatosis in the peripheral areas of the hepatic lobules and acute splenitis were observed, which are rare findings in acute arsenic poisoning. This study summarizes the histopathological features of arsenic poisoning and presents data on arsenic distribution. Arsenic concentrations in the liver and kidneys can increase the reliability of identifying arsenic poisoning. Furthermore, in traditional Chinese medicine-related deaths, arsenic poisoning needs more attention.

Biochar-Assisted Catalytic Pyrolysis of Oily Sludge to Attain Harmless Disposal and Residue Utilization for Soil Reclamation.

Pyrolysis of oily sludge (OS) is a feasible technology to match the principle of reduction and recycling; however, it is difficult to confirm the feasible environmental destination and meet the corresponding requirements. Therefore, an integrated strategy of biochar-assisted catalytic pyrolysis (BCP) of OS and residue utilization for soil reclamation is investigated in this study. During the catalytic pyrolysis process, biochar as a catalyst intensifies the removal of recalcitrant petroleum hydrocarbons at the expense of liquid product yield. Concurrently, biochar as an adsorbent can inhibit the release of micromolecular gaseous pollutants (e.g. HCN, H2S, and HCl) and stabilize heavy metals. Due to the assistance of biochar, pyrolysis reactions of OS are more likely to occur and require a lower temperature to achieve the same situation. During the soil reclamation process, the obtained residue as a soil amendment can not only provide a carbon source and mineral nutrients but can also improve the abundance and diversity of microbial communities. Thus, it facilitates the plant germination and the secondary removal of petroleum hydrocarbons. The integrated strategy of BCP of OS and residue utilization for soil reclamation is a promising management strategy, which is expected to realize the coordinated and benign disposal of more than one waste.

High nitrogen inhibits biomass and saponins accumulation in a medicinal plant Panax notoginseng.

Nitrogen (N) is an important macronutrient and is comprehensively involved in the synthesis of secondary metabolites. However, the interaction between N supply and crop yield and the accumulation of effective constituents in an N-sensitive medicinal plant Panax notoginseng (Burkill) F. H. Chen is not completely known. Morphological traits, N use and allocation, photosynthetic capacity and saponins accumulation were evaluated in two- and three-year-old P. notoginseng grown under different N regimes. The number and length of fibrous root, total root length and root volume were reduced with the increase of N supply. The accumulation of leaf and stem biomass (above-ground) were enhanced with increasing N supply, and LN-grown plants had the lowest root biomass. Above-ground biomass was closely correlated with N content, and the relationship between root biomass and N content was negatives in P. notoginseng (r = -0.92). N use efficiency-related parameters, NUE (N use efficiency, etc.), NC (N content in carboxylation system component) and P n (the net photosynthetic rate) were reduced in HN-grown P. notoginseng. SLN (specific leaf N), Chl (chlorophyll), NL (N content in light capture component) increased with an increase in N application. Interestingly, root biomass was positively correlated with NUE, yield and P n. Above-ground biomass was close negatively correlated with photosynthetic N use efficiency (PNUE). Saponins content was positively correlated with NUE and P n. Additionally, HN improved the root yield of per plant compared with LN, but reduced the accumulation of saponins, and the lowest yield of saponins per unit area (35.71 kg·hm-2) was recorded in HN-grown plants. HN-grown medicinal plants could inhibit the accumulation of root biomass by reducing N use and photosynthetic capacity, and HN-induced decrease in the accumulation of saponins (C-containing metabolites) might be closely related to the decline in N efficiency and photosynthetic capacity. Overall, N excess reduces the yield of root and C-containing secondary metabolites (active ingredient) in N-sensitive medicinal species such as P. notoginseng.

Clinical Efficacy of Minocycline Hydrochloride for the Treatment of Peri-Implant Disease: A Systematic Review With Meta-Analysis of Randomized Controlled Trials.

This systematic review aimed to assess the clinical efficacy of the local application of minocycline hydrochloride for treating peri-implantitis. Four databases-PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure-were searched from their inception through December 2020. English and Chinese randomized controlled trials (RCTs) that compared minocycline hydrochloride with control regimes, including negative control, iodine solution or glycerin, and chlorhexidine, for patients with peri-implant diseases were retrieved. Three outcomes-plaque index (PLI), probing depth (PD), and sulcus bleeding index (SBI)-were assessed using meta-analysis based on the random-effects model. Fifteen RCTs were included in the present meta-analysis, and results suggested that minocycline hydrochloride significantly affected PLI, PD, or SBI reduction regardless of the type of comparator regime. However, subgroup analyses suggested that minocycline hydrochloride was not superior to chlorhexidine in terms of reduction of PLI (1 week: MD = -0.18, 95% CI = -0.55 to 0.20, P = .36; 4 weeks: MD = -0.08, 95% CI = -0.23 to 0.07, P = .28; 8 weeks: MD = -0.01, 95% CI = -0.18 to 0.16, P = .91) and PD (1 week: MD = 0.07, 95% CI = -0.27 to 0.41, P = .68; 4 weeks: MD = -0.10, 95% CI = -0.43 to 0.24, P = .58; 8 weeks: MD = -0.30, 95% CI = -0.68 to 0.08, P = .12), and minocycline hydrochloride was also not better than chlorhexidine regarding reduction of SBI at 1 week after treatment (MD = -0.10; 95% CI = -0.21 to 0.01; P = .08). This study concludes that minocycline hydrochloride as adjuvant therapy of nonsurgical treatment enhances the clinical results when compared to control regimes. However, the difference between minocycline hydrochloride and chlorhexidine should be further investigated by designing additional high-quality studies with large sample sizes.

Dynamic change, influencing factors, and clinical impact of cellular components in human breast milk.

BACKGROUND: Numerous cellular components have been well demonstrated in human breast milk. However, little is known about their dynamic change, influencing factors, and potential clinical impacts on infants. METHODS: Sixty and forty-five healthy mother-infant pairs were enrolled in the colostrum group and mature milk group, respectively. Participants' demographic and clinical information were collected by questionnaires, and the infants were followed up until 6 months after birth through telephone interview. Colostrum and mature milk were collected, and the percentage of various cell components were determined by flow cytometric analysis. RESULTS: The results showed that, the total cell numbers, and the percentages of some stem cells, including CD34+, CD117+, CD133+, CD90+, CD105+, and CD146+ cells, were different in colostrum and mature milk. Besides, participants' characteristics had influence on the cellular components. Finally, high-CD34+ cells in colostrum, as well as the high-CD133+ cells and low-CD105+ cells in mature milk were associated with a significantly increased risk of infantile eczema within their first 3 months after birth. CONCLUSIONS: Our data showed a dynamic change of cellular components, identified some of their influencing factors and their potential clinical impacts on infantile eczema, which helps to better understand the cellular components in human breast milk. IMPACT: Some stem cell markers were dynamically changed in human colostrum and mature milk. Different cellular components were shown to be influenced by different participants' characteristics. High percentage of CD34+ cells in colostrum, as well as high percentage of CD133+ cells and low percentage of CD105+ cells in mature milk, were associated with a significantly increased risk of infantile eczema within their first 3 months after birth. To our knowledge, this is the first study on the clinical impacts of stem cells on infantile diseases, which helps to give a better understanding of human breast milk.

Screening of Antiviral Components of Yinhuapinggan Granule and Protective Effects of Yinhuapinggan Granule on MDCK Cells with Influenza A/H1N1 Virus.

BACKGROUND: Traditional Chinese medicine Yinhuapinggan granule (YHPG) has been used for treating upper respiratory tract infection like influenza, cough, and viral pneumonia. However, its active ingredients that really exert the main efficacy have not been well elucidated. This study is aimed at screening its antiviral components and investigating the potential therapeutic mechanisms of YHPG against the influenza A/PR8/34 (H1N1) virus in Madin Darby canine kidney (MDCK). METHODS: MDCK cells were infected with the influenza virus and then treated with ribavirin, YHPG, and main active ingredients in YHPG. Based on the maximum nontoxic concentration (TC0), half-maximal toxic concentration (TC50), half-maximal inhibitory concentration (IC50), and therapeutic index (TI), interferon-ß (IFN-ß) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the gene expression of TLR7, MyD88, tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Jun amino terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and p65 nuclear transcription factor-kappa B (p65 NF-κB) was quantified using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The results indicated that the components of YHPG, such as ephedrine hydrochloride, pseudoephedrine hydrochloride, chlorogenic acid, and emodin, had significant antiviral effects. High and medium doses of YHPG effectively reduced the cytopathic effect (CPE) and significantly decreased IFN-ß and IL-6 levels in the supernatant. Simultaneously, the transcript levels of TLR7, MyD88, TRAF6, JNK, p38 MAPK, and p65 NF-κB decreased in infected MDCK cells. Moreover, a certain dose-dependent relationship among different groups of YHPG was observed. CONCLUSIONS: These results indicated that YHPG and the components of YHPG had a significant inhibitory function on the proliferation of the H1N1 virus. The mechanism might be associated with suppressing the activation of the TLR7/MyD88 signaling pathway, a decrease in the mRNA expression of key target genes, and inhibition of IFN-ß and IL-6 secretion.

[Effect of acupuncture at Huatuo Jiaji (EX-B2) combined with core muscle training on motor function of lower limbs in patients with hemiplegia after stroke].

OBJECTIVE: To observe the effect of acupuncture at Huatuo Jiaji (EX-B2) combined with core muscle training on motor function of lower limbs, balance function and core muscle in patients with hemiplegia after stroke. METHODS: A total of ninety-six patients with hemiplegia after stroke were randomly and equally divided into acupuncture, training and combination groups (n=32 cases in each). Patients of the acupuncture group were given acupuncture at the 5th, 7th, 9th and 11th chest vertebrae, and the 1st to 5th lumbar vertebrae of EX-B2. Patients in the training group received core muscle training. In the combination group, both acupuncture treatment and core muscle training were given to the patients. The treatment was conducted once daily, 5 times a week for 4 weeks. The Fugl-Meyer lower limb motor function score (FMA), Berg balance function scale (BBS), Barthel index (BI) and surface electromyography (sEMG) of the erector spinae and rectus abdominis were evaluated before and after treatment and during the follow-up period. RESULTS: Compared with the scores before the treatment, the FMA, BBS and BI scores were obviously increased after the treatment and during the follow-up period in the three groups respectively (P<0.05). After treatment and during the follow-up period, the root mean square (RMS) of erector spinae and rectus abdominis in the sitting position flexed 45° and extended 30° on the healthy and affected side were higher than those of the same side before treatment in the three groups (P<0.05). The therapeutic effect of combination of acupuncture at EX-B2 and core muscle training was obviously superior to that of single acupuncture or single training (P<0.05). Before the treatment, the RMS of erector spinae and rectus abdominis in the sitting position flexed 45° and extended 30° on the affected side were lower than those of the healthy side in the three groups (P<0.05), while there was no significant difference between the RMS of the erector spinae and rectus abdominis of the affected side and the healthy side in the comprehensive group after treatment and during the follow-up period (P＞0.05). CONCLUSION: Acupuncture at EX-B2 combined with core muscle training can significantly improve the balance function and lower limb motor function of patients with hemiplegia after stroke.

The genome of medicinal leech (Whitmania pigra) and comparative genomic study for exploration of bioactive ingredients.

BACKGROUND: Leeches are classic annelids that have a huge diversity and are closely related to people, especially medicinal leeches. Medicinal leeches have been widely utilized in medicine based on the pharmacological activities of their bioactive ingredients. Comparative genomic study of these leeches enables us to understand the difference among medicinal leeches and other leeches and facilitates the discovery of bioactive ingredients. RESULTS: In this study, we reported the genome of Whitmania pigra and compared it with Hirudo medicinalis and Helobdella robusta. The assembled genome size of W. pigra is 177 Mbp, close to the estimated genome size. Approximately about 23% of the genome was repetitive. A total of 26,743 protein-coding genes were subsequently predicted. W. pigra have 12346 (46%) and 10295 (38%) orthologous genes with H. medicinalis and H. robusta, respectively. About 20 and 24% genes in W. pigra showed syntenic arrangement with H. medicinalis and H. robusta, respectively, revealed by gene synteny analysis. Furthermore, W. pigra, H. medicinalis and H. robusta expanded different gene families enriched in different biological processes. By inspecting genome distribution and gene structure of hirudin, we identified a new hirudin gene g17108 (hirudin_2) with different cysteine patterns. Finally, we systematically explored and compared the active substances in the genomes of three leech species. The results showed that W. pigra and H. medicinalis exceed H. robusta in both kinds and gene number of active molecules. CONCLUSIONS: This study reported the genome of W. pigra and compared it with other two leeches, which provides an important genome resource and new insight into the exploration and development of bioactive molecules of medicinal leeches.

In Silico Identification of Anti-SARS-CoV-2 Medicinal Plants Using Cheminformatics and Machine Learning.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, is spreading rapidly and has caused hundreds of millions of infections and millions of deaths worldwide. Due to the lack of specific vaccines and effective treatments for COVID-19, there is an urgent need to identify effective drugs. Traditional Chinese medicine (TCM) is a valuable resource for identifying novel anti-SARS-CoV-2 drugs based on the important contribution of TCM and its potential benefits in COVID-19 treatment. Herein, we aimed to discover novel anti-SARS-CoV-2 compounds and medicinal plants from TCM by establishing a prediction method of anti-SARS-CoV-2 activity using machine learning methods. We first constructed a benchmark dataset from anti-SARS-CoV-2 bioactivity data collected from the ChEMBL database. Then, we established random forest (RF) and support vector machine (SVM) models that both achieved satisfactory predictive performance with AUC values of 0.90. By using this method, a total of 1011 active anti-SARS-CoV-2 compounds were predicted from the TCMSP database. Among these compounds, six compounds with highly potent activity were confirmed in the anti-SARS-CoV-2 experiments. The molecular fingerprint similarity analysis revealed that only 24 of the 1011 compounds have high similarity to the FDA-approved antiviral drugs, indicating that most of the compounds were structurally novel. Based on the predicted anti-SARS-CoV-2 compounds, we identified 74 anti-SARS-CoV-2 medicinal plants through enrichment analysis. The 74 plants are widely distributed in 68 genera and 43 families, 14 of which belong to antipyretic detoxicate plants. In summary, this study provided several medicinal plants with potential anti-SARS-CoV-2 activity, which offer an attractive starting point and a broader scope to mine for potentially novel anti-SARS-CoV-2 drugs.

[Comparison of endogenetic microbial community diversity between wild Cordyceps sinensis,artificial C. sinensis and habitat soil].

To obtain the difference of the fungal and bacterial community diversity between wild Cordyceps sinensis, artificial C. sinensis and their habitat soil, Illmina Hiseq high-throughput sequencing technology was applied. The results show that Proteobacteria was the dominant bacterial phylum in C. sinensis, Actinobacteria was the dominant bacterial phylum in soil microhabitat, Ophiocordyceps sinensis was the predominant dominant fungus of C. sinensis. The α diversity analysis showed that the fungal diversity of stroma was lower than other parts, and the fungal diversity of wild C. sinensis was lower than that of artificial C. sinensis. The ß diversity analysis showed that the fungal and bacterial community diversity of soil microhabitat samples was significantly different from that of C. sinensis. The fungal community diversity was less different between wild and artificial C. sinensis, especially in sclerotia. LEfSe analysis showed a lot of species diversity between wild and artificial C. sinensis. Those different species between wild C. sinensis, artificial C. sinensis and their habitat soil provide ideas for further research on breed and components of C. sinensis.

Acupuncture Combined With Emotional Therapy of Chinese Medicine Treatment for Improving Depressive Symptoms in Elderly Patients With Alcohol Dependence During the COVID-19 Epidemic.

Objective: We aimed to analyze the characteristics and psychological mechanism of depressive symptoms in elderly patients with alcohol dependence under the COVID-19 epidemic and to observe the effect of acupuncture combined with emotional therapy of Chinese medicine treatment on depressive symptoms in elderly patients with alcohol dependence. Methods: Sixty patients were randomly divided into two groups. One group was treated by a set of emotional therapy of Chinese medicine treatment for 12 weeks (control group). One group was treated by a set of acupuncture combined with emotional therapy of Chinese medicine treatment for 12 weeks (treatment group). We compared the curative effect between the control group and the treatment group, the mean alcohol consumption, the SF-36 scores before and after treatment, and the scores of Hamilton Depression Scale before and after treatment of 3, 6, and 9 weeks. Results: Based on the cognitive behavior model, the characteristics and psychological mechanism of depression in elderly patients with alcohol dependence under the COVID-19 epidemic situation were summarized. The total effective rate of the control group was 60%, and that of the treatment group was 100% (p < 0.05). The alcohol consumption of the patients in each group decreased significantly after treatment (p < 0.05), and there was no significant difference in alcohol consumption between the treatment group and the control group (p > 0.05). After 12 weeks of treatment, there were significant differences in PF, RF, physical pain, general health status, energy, and mental health between the treatment group and the control group (p < 0.05). Before and after treatment, there were significant differences in PF, RF, physical pain, general health, energy, emotional function, and mental health (p < 0.05) of the treatment group. The PF, energy, and mental health of the control group were significantly different before and after treatment (p < 0.05). There was no significant difference between the treatment group and the control group in the scores of Hamilton Depression Scale before treatment. There was significant difference between the treatment group and the control group in the scores of Hamilton Depression Scale at 3, 6, and 9 weeks after treatment. Conclusion: Attention, cognition, emotion, behavior, and physical response reinforce each other, creating a vicious cycle that reinforces and sustains the depressive symptoms of elderly alcohol dependence under the COVID-19 epidemic, and acupuncture combined with emotional therapy of Chinese medicine treatment for improving the depressive symptoms of elderly alcohol dependence during the epidemic period of COVID-19 has a brilliant therapeutic effect.

Integrating chemical profiling and network pharmacology analysis based on anti-inflammatory effects for quality control of Scutellaria barbata.

INTRODUCTION: With the wide application of Scutellaria barbata D. Don for hepatitis and mastitis, its quality control issues have also received increasing attention. Based on the multi-component and multi-target characteristics of traditional Chinese medicine, there is an urgent need to establish a quality evaluation system. OBJECTIVES: This study intends to integrate the "quality-activity-quantification" strategy and establish an activity-related quality control method to ensure the safety and effectiveness of S. barbata. MATERIAL AND METHODS: Ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) was used to characterize the chemical components of S. barbata, and network pharmacological analysis was carried out on the identified components. The index components were determined on the basis of comprehensive activity prediction results and content information. At the same time, the contents of 16 batches of S. barbata from different origins were determined. RESULTS: A total of 94 compounds were identified according to mass spectrometric data, 12 of which were isolated and structure-confirmed by nuclear magnetic resonance technology. Network pharmacological analysis was applied to predict their key targets and the major pathways mediating their anti-inflammatory effects. On the basis of comprehensive activity prediction and content information, five components were chosen as crucial quality indicators of S. barbata, including scutellarin, scutellarein, luteolin, apigenin, and hispidulin. CONCLUSION: In this study, 16 different S. barbata batches were compared, and five quality indicators were determined on the basis of qualitative and activity results. The present study provides useful information for evaluating the quality of S. barbata in different areas, and also provides a new basis for the development of quality evaluation methods.

Usnic acid suppresses cervical cancer cell proliferation by inhibiting PD-L1 expression and enhancing T-lymphocyte tumor-killing activity.

The programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is abnormally expressed in cervical cancer cells. Moreover, PD-1/PD-L1 blockade reduces the apoptosis and exhaustion of T cells and inhibits the development of malignant tumors. Usnic acid is a dibenzofuran compound originating from Usnea diffracta Vain and has anti-inflammatory, antifungal, and anticancer activities. However, the molecular mechanism of its antitumor effects has not been fully elucidated. In this work, we first observed that usnic acid decreased the expression of PD-L1 in HeLa cells and enhanced the cytotoxicity of co-cultured T cells toward tumor cells. Usnic acid inhibited PD-L1 protein synthesis by reducing STAT3 and RAS pathways cooperatively. It was subsequently shown that usnic acid induced MiT/TFE nuclear translocation through the suppression of mTOR signaling pathways, and promoted the biogenesis of lysosomes and the translocation of PD-L1 to the lysosomes for proteolysis. Furthermore, usnic acid inhibited cell proliferation, angiogenesis, migration, and invasion, respectively, by downregulating PD-L1, thereby inhibiting tumor growth. Taken together, our results show that usnic acid is an effective inhibitor of PD-L1 and our study provide novel insights into the mechanism of its anticancer targeted therapy.

An integrative strategy for discovery of functional compound combination from Traditional Chinese Medicine: Danhong Injection as a model.

Traditional Chinese Medicine formulas, which are usually considered exerting their holistic clinical benefits via multi-component, multi-target manner, are unique resources for the discovery of multi-component drug combinations. In order to screen and optimize the functional compound combination (FCC) from TCM, we established a novel four-step 'GCIC' strategy, including 'Global profiling', 'Chemical structural classification', 'Intra-group screening' and 'Component-knockout optimization'. Following this strategy, an FCC consisted of four components from Danhong Injection (DHI) was identified, containing ferulic acid, cryptotanshinone, quercetin and anhydrosafflor yellow B. The holistic neuroprotective effects of the FCC were further investigated, indicating that the combination can both activate the antioxidative and anti-inflammatory responses in PC12 cells to protect them from oxidative stress. Major signaling pathways as Nrf2/ARE and Nrf2/AMPK/GSK3ß were involved in the protective process of FCC. The 'GCIC' strategy established in this study might provide an alternation to traditional strategies in discovering the bioactive components from herbal medicines, especially compounded TCM formulas.

Greener extraction process and enhanced in vivo bioavailability of bioactive components from Carthamus tinctorius L. by natural deep eutectic solvents.

Natural deep eutectic solvents (NaDESs) are promising green alternatives to conventional solvents widely applied in the extraction of natural products due to their physical and chemical superiorities. In present study, 22 NaDESs consisted from food grade ingredients were screened in ultrasonic assisted extraction (UAE) of bioactive compounds from safflower. The oral bioavailabilities of hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (ASYB) in the extracts were then investigated in SD rats with the help of HPLC-MS technique. The results revealed that l-proline-acetamide (l-Pro-Am) was an effective solvent with the yields of HSYA and ASYB at 32.83 and 8.80 mg/g. Pharmacokinetic studies revealed that the blood level of HSYA and ASYB were significantly higher after oral administration of l-Pro-Am extract than that of aqueous extract. Especially, the relative bioavailabilities (to aqueous extract) of HSYA and ASYB were calculated 183.5% and 429.8%.

Advanced High-Performance Potassium-Chalcogen (S, Se, Te) Batteries.

Current great progress on potassium-chalcogen (S, Se, Te) batteries within much potential to become promising energy storage systems opens a new avenue for the rapid development of potassium batteries as a complementary option to lithium ion batteries. The discussion mainly concentrates on recent research advances of potassium-chalcogen (S, Se, Te) batteries and their corresponding cathode materials in this review. Initially, the development of cathode materials for four types of batteries is introduced, including: potassium-sulfur (K-S), potassium-selenium (K-Se), potassium-selenium sulfide (K-Sex Sy ), and potassium-tellurium (K-Te) batteries. Next, critical challenges for chalcogen-based electrodes in devices operation are summarized. In addition, some pragmatic strategies are proposed as well to relieve the low electronic conductivity, large volumetric expansion, shuttle effect, and potassium dendrite growth. At last, the perspectives on designing advanced cathode materials for potassium-chalcogen batteries are provided with the goal of developing high-performance potassium storage devices.