CsREV-CsTCP4-CsVND7 module shapes xylem patterns differentially between stem and leaf to enhance tea plant tolerance to drought.

Cultivating drought-tolerant tea varieties enhances both yield and quality of tea plants in northern China. However, the mechanisms underlying their drought tolerance remain largely unknown. Here we identified a key regulator called CsREV, which differentially regulates xylem patterns between leaves and stems, thereby conferring drought tolerance in tea plants. When drought occurs, upregulation of CsREV activates the CsVND7a-dependent xylem vessel differentiation. However, when drought persists, the vessel differentiation is hindered as CsVND7a is downregulated by CsTCP4a. This, combined with the CsREV-promoted secondary-cell-wall thickness of xylem vessel, leads to the enhanced curling of leaves, a characteristic closely associated with plant drought tolerance. Notably, this inhibitory effect of CsTCP4a on CsVND7a expression is absent in stems, allowing stem xylem vessels to continuously differentiate. Overall, the CsREV-CsTCP4-CsVND7 module is differentially utilized to shape the xylem patterns in leaves and stems, potentially balancing water transportation and utilization to improve tea plant drought tolerance.

Simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) by probe-type ultrasound-assisted natural deep eutectic solvents and their inhibition effects on low density lipoprotein oxidation.

The simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) was performed by integrating natural deep eutectic solvents (NADES) and ultrasound-assisted extraction (UAE). Among the eight kinds of NADES screened, choline chloride-1,2-propylene glycol was the most suitable extractant. The probe-type ultrasound-assisted NADES extraction system (pr-UAE-NADES) demonstrated higher extraction efficiency compared with plate-type ultrasound-assisted NADES extraction system (pl-UAE-NADES). Orthogonal experimental design and a modified multi-index synthetic weighted scoring method were adopted to optimize pr-UAE-NADES extraction process. The optimal extraction conditions that had a maximum synthetic weighted score of 29.46 were determined to be 25 °C for extraction temperature, 600 W for ultrasonic power, 20 min for extraction time, and 25% (w/w) for water content in NADES, leading to the maximum yields (7.39 ± 0.20 mg/g and 57.99 ± 0.91 mg/g, respectively) of crocin and geniposide. Thirty-three compounds including iridoids, carotenoids, phenolic acids, flavonoids, and triterpenes in the NADES extract were identified by LC-Q-TOF-MS2 coupled with a feature-based molecular networking workflow. The kinetics evaluation of the conjugated dienes generation on Cu2+-induced low density lipoprotein (LDL) oxidation via the four-parameter logistic regression model showed that crocin increased the lag time of LDL oxidation in a concentration-dependent manner (15 µg/mL, 30 µg/mL, 45 µg/mL) by 12.66%, 35.44%, and 73.42%, respectively. The quantitative determination for fluorescence properties alteration of the apolipoprotein B-100 exhibited that crocin effectively inhibited the fluorescence quenching of tryptophan residues and the modification of lysine residues caused by reactive aldehydes and malondialdehydes. The pr-UAE-NADES showed significant efficiency toward the simultaneous extraction of crocin and geniposide from gardenia fruits. And this study demonstrates the potential utility of gardenia fruits in developing anti-atherogenic functional food.

p-Type Two-Dimensional Semiconductors: From Materials Preparation to Electronic Applications.

Two-dimensional (2D) materials are regarded as promising candidates in many applications, including electronics and optoelectronics, because of their superior properties, including atomic-level thickness, tunable bandgaps, large specific surface area, and high carrier mobility. In order to bring 2D materials from the laboratory to industrialized applications, materials preparation is the first prerequisite. Compared to the n-type analogs, the family of p-type 2D semiconductors is relatively small, which limits the broad integration of 2D semiconductors in practical applications such as complementary logic circuits. So far, many efforts have been made in the preparation of p-type 2D semiconductors. In this review, we overview recent progresses achieved in the preparation of p-type 2D semiconductors and highlight some promising methods to realize their controllable preparation by following both the top-down and bottom-up strategies. Then, we summarize some significant application of p-type 2D semiconductors in electronic and optoelectronic devices and their superiorities. In end, we conclude the challenges existed in this field and propose the potential opportunities in aspects from the discovery of novel p-type 2D semiconductors, their controlled mass preparation, compatible engineering with silicon production line, high-κ dielectric materials, to integration and applications of p-type 2D semiconductors and their heterostructures in electronic and optoelectronic devices. Overall, we believe that this review will guide the design of preparation systems to fulfill the controllable growth of p-type 2D semiconductors with high quality and thus lay the foundations for their potential application in electronics and optoelectronics.

Magnesium transporter CsMGT10 of tea plants plays a key role in chlorosis leaf vein greening.

Magnesium (Mg2+), as the central atom of chlorophyll, is the most abundant divalent cation for plant growth and development in living cells. MRS2/MGT magnesium transporters play important roles in coping with magnesium stress, chloroplast development and photosynthesis. However, the molecular mechanism of MGT influencing tea plant leaf vein color remains unknown. Here, we demonstrate that CsMGT10 may be a potential transporter influencing leaf vein color. CsMGT10 belongs to Clade A member of MRS2/MGT family. CsMGT10 has the highest expression level in leaves of tea plants. And it is mainly expressed in aboveground parts, especially in vascular bundles. Moreover, CsMGT10 localizes to the chloroplast envelope of tea plants with a high affinity to Mg2+. And the GMN motif is required for its magnesium transport function. Ectopic expression of CsMGT10 in Arabidopsis leaf variegation mutant var5-1 can restore green color of chlorosis leaf veins, and the contents of chlorophyll and carotenoid change significantly, proving its essential role in leaf vein greening. Furthermore, the chlorophyll and carotenoid of tea leaves treated with CsMGT10 antisense oligonucleotides also decrease significantly. Our findings indicate that CsMGT10 mainly acts as Mg2+ transporter in chloroplast envelope of leaf veins, which may play a key role in leaf vein greening of tea plants.

Lipid-Based Nanocarriers Enabled Oral Delivery of Oleanolic Acid Derivative DKS26 for Diabetes Management.

Oleanolic acid derivative DKS26 has hypolipidemic, islet, and hepatoprotective effects. However, high lipophilicity and low water solubility led to DKS26 extremely low oral bioavailability. Herein, lipid-based nanocarriers, including lipid nanodiscs (sND/DKS26) and liposomes (sLip/DKS26), are prepared to improve DKS26 oral absorption. In comparison to free DKS26 (5.81%), the absolute oral bioavailabilities are significantly increased to 29.47% (sND/DKS26) and 37.25% (sLip/DKS26) without detectable toxicity or immunogenicity even after repeated administrations. Both sND/DKS26 and sLip/DKS26 significantly reduce the feeding glucose level and the AUC of OGTT in db/db diabetic mice. Aiding by the newly developed scFv-based nanocarrier separation methods, no intact nanocarriers are detected in blood circulation after oral administration, suggesting that both formulations are unable to penetrate the intestinal epithelium. They enhance DKS26 absorption mainly by improving intestinal cell uptake and rapid intracellular release of the payload. Since pre-existing anti-PEG is widely detected in humans, the present oral absorption pathway of both nanocarriers successfully avoids unfavorable immunological responses after interaction with anti-PEG antibodies. The application of lipid-based nanocarriers paves an efficient and safe avenue for the clinical translation and application of poorly soluble therapeutics derived from traditional Chinese medicine.

TMT quantitative proteomics and network pharmacology reveal the mechanism by which asiaticoside regulates the JAK2/STAT3 signaling pathway to inhibit peritoneal fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine, Centella asiatica (L.) Urb., has been extensively utilized in clinics to treat a variety of fibrotic disorders. Asiaticoside (ASI), as an important active ingredient, has attracted much attention in this field. However, the effect of ASI on peritoneal fibrosis (PF) is still unclear. Therefore, we evaluated the benefits of ASI for PF and mesothelial-mesenchymal transition (MMT) and revealed the underlying mechanisms. AIM OF STUDY: The objective of this investigation was to anticipate the potential molecular mechanism of ASI against peritoneal mesothelial cells (PMCs) MMT employing proteomics and network pharmacology, and to confirm it using in vivo and in vitro studies. MATERIALS AND METHODS: The mesentery of peritoneal fibrosis mice and normal mice were analyzed quantitatively for proteins that were differentially expressed using a technique tandem mass tag (TMT). Next, the core target genes of ASI against PF were screened through network pharmacology analysis, and PPI and C-P‒T networks were constructed by Cytoscape Version 3.7.2. According to the findings of a GO and KEGG enrichment analysis of differential proteins and core target genes, the signaling pathway with a high correlation degree was selected as the key signaling pathway of ASI inhibiting the PMCs MMT for further molecular docking analysis and experimental verification. RESULTS: TMT-based quantitative proteome analysis revealed the identification of 5727 proteins, of which 70 were downregulated and 178 were upregulated. Among them, the levels of STAT1, STAT2, and STAT3 in the mesentery of mice with peritoneal fibrosis were considerably lower than in the control group, indicating a role for the STAT family in the pathogenesis of peritoneal fibrosis. Then, a total of 98 ASI-PF-related targets were identified by network pharmacology analysis. JAK2 is one of the top 10 core target genes representing a potential therapeutic target. JAK/STAT signaling may represent a core pathway mediating PF effects by ASI. Molecular docking studies showed that ASI had the potential to interact favorably with target genes involved in the JAK/STAT signaling pathway, such as JAK2 and STAT3. The experimental results showed that ASI could significantly alleviate Chlorhexidine Gluconate (CG)-induced peritoneal histopathological changes and increase JAK2 and STAT3 phosphorylation levels. In TGF-ß1-stimulated HMrSV5 cells, E-cadherin expression levels were dramatically reduced whereas Vimentin, p-JAK2, α-SMA, and p-STAT3 expression levels were considerably increased. ASI inhibited the TGF-ß1-induced HMrSV5 cell MMT, decreased the activation of JAK2/STAT3 signaling, and increased the nuclear translocation of p-STAT3, which was consistent with the effect of the JAK2/STAT3 pathway inhibitor AG490. CONCLUSION: ASI can inhibit PMCs MMT and alleviate PF by regulating the JAK2/STAT3 signaling pathway.

Munronin V with 7/7/6 tricarbocyclic framework from Munronia henryi harms inhibits tau pathology by activating autophagy.

Munronin V (1), isolated from Munronia henryi Harms, is the first example, to the best of our knowledge, of an unprecedented 7/7/6 tricarbocyclic framework featuring an unusual A,B-seco-limonoid ring. The structures of munronin V were established from extensive spectroscopic and electronic circular dichroism (ECD) analyses. The novel A,B-seco with two seven-membered lactones was formed as a result of Baeyer-Villiger oxidation. Compound 1 activated autophagy and inhibited Tau pathology as revealed by flow cytometric analyses, confocal imaging analysis and western blotting, and this effect was mediated by transcription factor EB (TFEB). These findings suggested that 1 might have potential as a compound for combating Alzheimer's disease.

A novel and alternative therapy for persistent allergic rhinitis via intranasal acupuncture: a randomized controlled trial.

BACKGROUND: Acupuncture is used to treat allergic rhinitis (AR) in traditional Chinese medicine, and the ST2 and ST36 acupoints are generally selected in clinical practice. We report a new intranasal acupuncture method at the Neiyingxiang (EX-HN9) and Biqiu points for the treatment of persistent AR (PAR). Here, the efficacy and safety of this method were evaluated. METHODS: A total of 120 patients diagnosed with PAR were randomly allocated (2:1 ratio) to intranasal acupuncture or Western medicine groups, the basic principle of random grouping is SAS random grouping method. The applicator held a nasal endoscope and a 0.30 × 75 mm filiform needle in their left and right hands, respectively. When aiming at the Neiyingxiang or Biqiu point, the applicator quickly inserted the needle to a 20-mm depth as parallel as possible to the inferior turbinate or middle turbinate, without special reinforcing and reducing techniques (the needle remained for 20 min). The intranasal acupuncture groups received acupuncture treatment three times per week for 2 weeks. The Western medicine group was treated with budesonide nasal spray (two sprays/nostril, twice/day) and loratadine (one tablet/night) for 2 weeks. Visual analog scale (VAS) scores were the primary outcome. Quality of life, medication dosages and adverse events were secondary outcomes measured using the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). Confidence assessments were performed to evaluate data from the treatment and follow-up periods. RESULTS: The results were as follows: (1) VAS and RQLQ scores were significantly lower in the intranasal acupuncture group than in the Western medicine group on day 1 (i.e., first treatment) (P < 0.05; 95% CI - 13.1 to - 9.6 VAS points) (P < 0.05; 95% CI - 20.27 to - 12.28 RQLQ points). Overall symptoms (95% CI - 2.86 to - 1.86 points), nasal obstruction (95% CI - 6.33 to - 5.36 points), olfactory function (95% CI - 2.91 to - 1.75 points), sleep (95% CI - 5.05 to - 3.57 points), actual problems (95% CI - 2.03 to - 0.06 points), nasal symptoms (95% CI - 6.62 to - 4.5 points), and emotional problems (95% CI - 5.05 to - 3.5 points) were significantly improved. (2) VAS and RQLQ scores in the two groups were significantly improved at week 2; however, there were no significant group differences in the VAS (P > 0.05; 95% CI - 1.21 to - 1.38 points) and RQLQ (P > 0.05; 95% CI - 0.33 to - 3.46 points) scores. Olfactory function symptoms were significantly improved (95% CI - 1.58 to - 0.21 points). (3) During the follow-up period, there was a significant difference between the two groups (P < 0.05) with higher RQLQ and VAS scores in the intranasal acupuncture group than in the Western medicine group. VAS scores on rhinobyon symptoms, nasal itch, rhinorrhea and olfactory function and RQLQ scores for activities, non-nasal/eye symptoms, actual problems, nasal symptoms, and eye symptoms were significantly improved. (4) No adverse events were observed in either group during treatment. CONCLUSIONS: Intranasal acupuncture has good efficacy and safety in the treatment of PAR. Moreover, VAS and RQLQ scores were much lower in the intranasal acupuncture group than in the Western medicine group, and acupuncture had an immediate impact, especially for improving nasal congestion, olfactory function and sleep.

Effect of folic acid supplementation on the change of plasma S-adenosylhomocysteine level in Chinese hypertensive patients: a randomized, double-blind, controlled clinical trial.

The relationship between folic acid and S-adenosylhomocysteine (SAH) is controversial. This study aims to explore the effect of different doses of folic acid supplementation on SAH levels in hypertensive patients and the modification of methylene-tetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A randomized, double-blind, controlled clinical trial was conducted. Hypertensive patients aged 45-75 years without a history of stroke and cardiovascular disease were selected, who were randomly assigned to one of 8 dose groups. This trial has been registered with Trial Number: ChiCTR1800016135. In the total population, folic acid supplementation of 0.4-2.0 mg/day had no effect on SAH level (ß = 0.47, 95% CI: -0.86-1.79, p = 0.491), while folic acid supplementation of 2.4 mg/day significantly increased SAH level (ß = 1.93, 95% CI: 0.22-3.64, p = 0.027). Stratified analysis found that MTHFR C677T genotype CC supplemented with 2.4 mg/day folic acid had no effect on SAH level (ß = 0.30, 95% CI: -2.74-3.34, p = 0.847), while CT and TT genotype supplemented with 2.4 mg/day folic acid showed a significant increase in SAH level (CT: ß = 2.98, 95% CI: 0.34-5.62, p = 0.027; TT: ß = 3.00, 95% CI: -0.51-6.51, p = 0.095; CT combined with TT: ß = 2.99, 95% CI: 0.90-5.09, p = 0.005). In conclusion, supplementation of 2.4 mg/day folic acid can lead to increased SAH levels, especially in MTHFR C677T genotype CT and TT.

Re-interpretation of the mechanism of type 2 diabetes mellitus based on a framework of psychosomatic medicine: a real-world study.

OBJECTIVE: Using bipolar disorder (BD) as a control, we explored the possible developmental process of impaired glucose metabolism rhythm. METHODS: In total, 441 subjects (77, 162, 134, 54, and 14 in the pre-diabetes [pre-DM], DM, BD, BD + pre-DM, and BD + DM groups, respectively) and 160 controls were included. All subjects were assessed using the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes were measured. RESULTS: Cluster analysis showed that the BD, BD + DM, and DM groups were classified as the 'disease group, the BD + pre-DM group as the 'mixed period group', and the pre-DM group as the 'pre-disease group'. The conscientiousness factor scores of the NEO-FFI in the 'disease group' were higher than the norm but lower than the norm in the 'pre-disease group'. The scores of neurotic factors in the 'pre-disease' and 'mixed period' groups were both significantly higher than that in the 'disease group' (corrected p < 0.001). The incidences of the abnormal HPA axis decreased gradually from the 'pre-disease group' to the 'mixed period group' then to the 'disease group', while those of the HPT axis slightly increased at first and then significantly decreased. The overall prediction rate of the multiple logistic regression model was 92.7%. CONCLUSION: This study suggests that progression of pre-diabetes to DM is a continuous process from local abnormalities to rhythm disorder of glucose metabolism. This understanding can be applied to the whole course management and early intervention of DM and to the future development of optimised treatment based on rhythm regulation. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Identify and the optimization of treatment for non-infectious chronic diseases under the "stress-dysrhythmia" theory hypothesis (Registration date: 24/10/2018). The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).

Sex-specific association between coffee consumption and incident chronic kidney disease: a population-based analysis of 359,906 participants from the UK Biobank.

BACKGROUND: The risk for chronic kidney disease (CKD) is influenced by genetic predisposition, sex, and lifestyle. Previous research indicates that coffee is a potentially protective factor in CKD. The current study aims to investigate whether sex disparity exists in the coffee-CKD association, and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association. METHODS: A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study, which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model. Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data ( n = 255,343). Analyses stratified by genetic predisposition, comorbidities, and sex hormones were performed. Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results. RESULTS: Coffee was inversely associated with CKD in a dose-dependent manner. The effects of coffee did not differ across different strata of genetic risk for CKD, but were more evident among slower genetically predicted caffeine metabolizers. Significant sex disparity was observed ( P value for interaction = 0.013), in that coffee drinking was only associated with the risk reduction of CKD in females. Subgroup analysis revealed that testosterone and sex hormone-binding globulin (SHBG), but not estradiol, modified the coffee-CKD association. CONCLUSIONS: In addition to the overall inverse coffee-CKD association that was observed in the general population, we could also establish that a sex disparity existed, in that females were more likely to experience the benefit of the association. Testosterone and SHBG may partly account for the sex disparity.

Evaluation of the antimicrobial function of Ginkgo biloba exocarp extract against clinical bacteria and its effect on Staphylococcus haemolyticus by disrupting biofilms.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Ginkgo biloba L. (Ginkgo nuts) has been used for a long time as a critical Chinese medicine material to treat cough and asthma, as well as a disinfectant. Similar records were written in the Compendium of Materia Medica (Ben Cao Gang Mu, pinyin in Chinese) and Sheng Nong's herbal classic (Shen Nong Ben Cao Jing, pinyin in Chinese). Recent research has shown that Ginkgo biloba exocarp extract (GBEE) has the functions of unblocking blood vessels and improving brain function, as well as antitumour activity and antibacterial activity. GBEE was shown to inhibit methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation as a traditional Chinese herb in our previous report in this journal. AIM OF THE STUD: yThe antibiotic resistance of clinical bacteria has recently become increasingly serious. Thus, this study aimed to investigate the Ginkgo biloba exocarp extract (GBEE) antibacterial lineage, as well as its effect and mechanism on S. haemolyticus biofilms. This study will provide a new perspective on clinical multidrug resistant (MDR) treatment with ethnopharmacology herbs. METHODS: The microbroth dilution assay was carried out to measure the antibacterial effect of GBEE on 13 types of clinical bacteria. Bacterial growth curves with or without GBEE treatment were drawn at different time points. The potential targets of GBEE against S. haemolyticus were screened by transcriptome sequencing. The effects of GBEE on bacterial biofilm formation and mature biofilm disruption were determined by crystal violet staining and scanning electron microscopy. The metabolic activity of bacteria inside the biofilm was assessed by colony-forming unit (CFU) counting and (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2HY-tetrazolium bromide (MTT) assay. Quantitative polymerase chain reaction (qPCR) was used to measure the gene expression profile of GBEE on S. haemolyticus biofilm-related factors. RESULTS: The results showed that GBEE has bacteriostatic effects on 3 g-positive (G+) and 2 g-negative (G-) bacteria among 13 species of clinical bacteria. The antibacterial effect of GBEE supernatant liquid was stronger than the antibacterial effect of GBEE supernviaould-like liquid. GBEE supernatant liquid inhibited the growth of S. epidermidis, S. haemolyticus, and E. faecium at shallow concentrations with minimum inhibitory concentrations (MICs) of 2 µg/ml, 4 µg/ml and 8 µg/ml, respectively. Genes involved in quorum sensing, two-component systems, folate biosynthesis, and ATP-binding cassette (ABC) transporters were differentially expressed in GBEE-treated groups compared with controls. Crystal violet, scanning electron microscopy (SEM) and MTT assays showed that GBEE suppressed S. haemolyticus biofilm formation in a dose-dependent manner. Moreover, GBEE supernatant liquid downregulated cidA, cidB and atl, which are involved in cell lysis and extracellular DNA (eDNA) release, as well as downregulated the cbp, ebp and fbp participation in encoding cell-surface binding proteins. CONCLUSIONS: GBEE has an excellent antibacterial effect on gram-positive bacteria and also inhibits the growth of gram-negative bacteria, such as A. baumannii (carbapenem-resistant Acinetobacter baumannii) CRABA and S. maltophilia. GBEE inhibits the biofilm formation of S. haemolyticus by altering the regulation and biofilm material-related genes, including the release of eDNA and cell-surface binding proteins.

A NIR-II light-modulated injectable self-healing hydrogel for synergistic photothermal/chemodynamic/chemo-therapy of melanoma and wound healing promotion.

The development of an injectable multifunctional hydrogel with tumor therapy, antibacterial treatment and wound healing properties is essential for simultaneously eradicating melanoma and promoting wound healing of tumor-initiated skin defects. Herein, iron ion-doped polyaniline (PANI(Fe)) tethered with guar gum (GG) chains is employed for the first time as a building unit for constructing a superior hydrogel (GG@PANI(Fe)-borax) crosslinked by borate/didiol bonds. Due to the dynamic and reversible properties of boronate ester bonds, the GG@PANI(Fe)-borax hydrogels had convenient injectability, rapid self-healing ability, and reversible gel-sol transformations under thermal- or pH-stimuli. More importantly, they took advantage of the second near-infrared (NIR-II) responsive photothermal conversion capability, accompanied by the photothermal-enhanced high cytotoxic ˙OH generation in the H2O2-enriched tumor microenvironment induced by iron-doped PANI. The as-prepared hydrogels exhibited excellent photothermal effects and controllable NIR-triggered drug release, leading to distinctly synergistic photothermal/chemodynamic/chemo-therapy effects of melanoma both in vitro (98.2%) and in vivo (98.8%). In addition, the obtained hydrogels also exhibited good anti-bacterial activity (>97.1%) against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria because they were based on PANI(Fe) and borax, which exhibit antibacterial activity. Furthermore, these GG@PANI(Fe)-incorporated scaffolds could improve fibroblast cell proliferation and angiogenesis for accelerating wound repair in tumor-bearing and infected wound mice. Taken together, GG@PANI(Fe)-borax hydrogels may be used simultaneously for eradication of skin-tumor cells, inhibiting infection and accelerating wound healing. This work offers an effective and facile strategy to fabricate an "all-in-one" multifunctional hydrogel platform for synergetic multimodal integrated therapy of tumors.

Pharmacological Mechanism of Shen Huang Chong Ji for Treating Alzheimer's Disease Based on Network Pharmacology and Experimental Validation.

The traditional Chinese medicine (TCM) formula, Sheng Huang Chong Ji (SHCJ) is largely applied for treating Alzheimer's disease (AD), but not much is known regarding its active compounds, molecular targets, and mechanism of action. The current study aimed to predict the potential molecular mechanism of SHCJ against AD based on network pharmacology combined with in vitro validation. Using public databases, SHCJ's active compounds, their potential targets, and AD-related genes were screened, while Cytoscape Version 3.7.2 was used to build protein-protein interaction (PPI) and compound-disease-target (C-D-T) networks. Analysis of enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms was then carried out in R 4.0.2, including associated packages. Subsequently, molecular docking analysis was performed with AutoDock Vina 1.1.2, with intro experiments involving SH-SY5Y cells used to further investigate the mechanism of SHCJ against AD. Finally, a total of 56 active compounds of SHCJ and 192 SHCJ-AD-related targets were identified. Quercetin was identified as the top potential candidate agent. HSP90AA1, AKT1, and MAPK1 represent potential therapeutic targets. The PI3K-Akt signaling pathway potentially represents a core one mediating the effects of SHCJ against AD. Additionally, molecular docking analysis indicated that quercetin could combine well with AKT1 and multiple apoptosis-related target genes. During cell experiments, a significant increase in cell viability along with a decrease in Aß 25-35-induced apoptosis was observed after treatment with SHCJ. Furthermore, SHCJ significantly increased the phosphorylation of PI3K and Akt while reversing Aß 25-35-induced apoptosis-related protein expression downregulation.

Anti-TMV effects of seco-pregnane C21 steroidal glycosides isolated from the roots of Cynanchum paniculatum.

Tobacco mosaic virus (TMV) is known to infect a wide range of plants, resulting in reduced yield and productivity. Novel, effective, and plant-based pesticides are required to protect plants against TMV infection. To identify novel anti-TMV agents from natural sources, we systematically studied the roots of Cynanchum paniculatum and isolated six new seco-pregnane C21 steroidal glycosides, along with 14 known compounds. Their structures were elucidated by comprehensive spectroscopic data analysis. The anti-TMV activity of compounds were screened using the half-leaf method. Biological tests revealed that compounds 1, 2, 5, 9, 10, 15, and 16 displayed significant anti-TMV activities compared with the positive control ningnanmycin. In addition, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis confirmed the antiviral activity of these compounds, as evident from reduced TMV coat protein (TMV-CP) gene replication and TMV-CP protein expression. These compounds downregulated the expression of NtHsp70-1 and NtHsp70-261, indicating that these steroidal glycosides possibly inhibit the TMV infection by suppressing the expression of NtHsp70-1 and NtHsp70-061 expression.

Tanshinone Capsules Combined With Prednisone for Facial Seborrheic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Facial seborrheic dermatitis (FSD), also called facial seborrheic eczema, is a common disease affecting both male and female patients worldwide. Tanshinone is the main bioactive component extracted from the Traditional Chinese Medicine Salvia miltiorrhiza Bunge, which is widely used in treating skin inflammatory diseases. It is necessary to evaluate the clinical evidence for tanshinone capsule treatment of FSD. This study aimed to evaluate the safety and effectiveness of tanshinone capsules combined with prednisone in the treatment of facial seborrheic dermatitis and to provide evidence for clinical practice. Methods: Studies were searched in PubMed, the Cochrane Library, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, and WanFang Database before October 2021. We also searched for randomized controlled clinical trials (RCT) of tanshinone capsules combined with prednisone on facial seborrheic dermatitis. The meta-analysis was conducted according to the guidelines of the Cochrane Handbook. Two reviewers regulated the research selection, data extraction, and risk of bias assessment, respectively, and a third reviewer was used for consulting when necessary. Review Manager Software 5.3 was used for meta-analysis. Results: A total of 10 RCTs with 916 participants were included. Nine studies reported total effectiveness, five studies reported symptom score, seven studies reported adverse events, and four studies reported recurrence rate. The duration of treatment was 4 to 8 weeks. Combination therapy showed better clinical effects compared to the prednisone (OR: 5.82; 95% CI: 3.53, 9.59; p < 0.00001). Combination therapy could repair skin lesions (MD: -0.40; 95% CI: -0.51, -0.30; p < 0.00001), reduce skin erythema (MD: -0.58, 95% CI: -0.67, -0.49; p < 0.00001), relieve skin itch (MD: -0.70; 95% CI -0.77, -0.63; p < 0.00001), and desquamation score (MD: -0.64; 95% CI: -0.71, -0.56; p < 0.00001). Furthermore, combination therapy could reduce adverse events (OR: 0.46; 95% CI: 0.26, 0.84; p = 0.01) and control recurrence rate (OR: 0.22; 95% CI: 0.13, 0.36; p < 0.00001). Conclusions: Compared with prednisone, tanshinone capsules combined with prednisone may be effective in the treatment of facial seborrheic dermatitis. However, due to the high risk and ambiguity of bias in the included trials, the conclusion of this study must be interpreted carefully.

Synthesis and biological evaluation of cajanonic acid A derivatives as potential PPARγ antagonists.

Four series of cajanonic acid A (CAA) derivatives have been designed and synthesized. The newly prepared compounds have been screened for glucose consumption activity in HepG2 cell lines and PPARγ antagonistic activity in HEK293 cell lines. Compound 26g bearing a tetrahydroisoquinolinone scaffold showed the most potent PPARγ antagonistic and hypoglycemic activities. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 26g was a potent hypoglycemic agent. In addition, the possible binding modes for compound 26g in the PPARγ protein have been investigated in this study.

Non-targeted analysis of vulgarisins by using collisional dissociation mass spectrometry for the discovery of analogues from Prunella vulgaris.

Vulgarisins are members of diterpenoids with rare 5/6/4/5 ring skeleton from Prunella vulgaris Linn. (P. vulgaris). Their molecular scaffolds comprise different hydroxylation and degree of esterification. Vulgarisins have attracted many attentions in the fields of food and medicine for their potent bioactivities. Firstly, four reference compounds were analyzed by higher-energy collisional dissociation mass spectrometry (HCD MS/MS) and the fragmentation patterns for molecular scaffold were summarized. And then, a high-performance liquid chromatography/electrospray ionization/high-resolution mass spectrometry (HPLC-ESI-HR-MS) method was adopted to investigate the P. vulgaris extracts. Finally, the proposed analysis results were successfully applied to facilitate the discovery of the vulgarisins analogues from P. vulgaris. For the four reference compounds, the sodium adduct was the predominate ion in full scan. A specific fragmentation pathway of [M+Na]+ ions leads to produce diagnostic ions of vulgarisins at m/z 325 under HCD, which was formed through consecutive-side chains lost. Twenty-three diterpenoids, including 18 vulgarisins analogues, were identified or tentatively characterized in the botanical extracts of P. vulgaris based on their elemental constituents and characteristic fragment ion profiles. Two new vulgarisins analogues in the plant were isolated and their structures were illustrated based on extensive spectroscopic analysis using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. The HCD MS/MS method, including the profiles of the diagnostic ions induced by characteristic fragmentation, is an effective technique for the discovery of vulgarisins analogues in P. vulgaris. The expected fragmentation pattern knowledge will also facilitate the analysis of other natural products.

[Research progress on anti-tumor effect of Chinese dragon's blood].

As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.