[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

Magnetic Bimetallic Heterointerface Nanomissiles with Enhanced Microwave Absorption for Microwave Thermal/Dynamics Therapy of Breast Cancer.

Microwave thermotherapy (MWT) has shown great potential in cancer treatment due to its deep tissue penetration and minimally invasive nature. However, the poor microwave absorption (MA) properties of the microwave thermal sensitizer in the medical frequency band significantly limit the thermal effect of MWT and then weaken the therapeutic efficacy. In this paper, a Ni-based multilayer heterointerface nanomissile of MOFs-Ni-Ru@COFs (MNRC) with improved MA performance in the desired frequency band via introducing magnetic loss and dielectric loss is developed for MWT-based treatment. The loading of the Ni nanoparticle in MNRC mediates the magnetic loss, introducing the MA in the medical frequency band. The heterointerface formed in the MNRC by nanoengineering induces significant interfacial polarization, increasing the dielectric loss and then enhancing the generated MA performance. Moreover, MNRC with the strong MA performance in the desired frequency range not only enhances the MW thermal effect of MWT but also facilitates the electron and energy transfer, generating reactive oxygen species (ROS) at tumor sites to mediate microwave dynamic therapy (MDT). The strategy of strengthening the MA performance of the sensitizer in the medical frequency band to improve MWT-MDT provides a direction for expanding the clinical application of MWT in tumor treatment.

Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes.

The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications. Here, we report results generated using a recently streamlined pipeline approach for the evaluation of the effects of chemical compounds on lifespan and health. We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies-for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions.

Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway.

BACKGROUND: Jujuboside B (JuB) is the main bioactive saponin component of Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen, which has been reported to possess varied pharmacological functions. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of JuB on acetaminophen (APAP) overdose-induced hepatotoxicity have not been determined yet. METHODS: C57BL/6 J mice were pre-treated with JuB (20 or 40 mg/kg) for seven days before APAP (400 mg/kg) injection. After 24 h of APAP treatment, serum, and liver tissues were collected to evaluate the therapeutic effects. To investigate whether the Nrf2-STING signaling pathway is involved in the protective effects of JuB against APAP-induced hepatotoxicity, the mice received the DMXAA (the specific STING agonist) or ML385 (the specific Nrf2 inhibitor) during the administration of JuB, and Hematoxylin-eosin staining, Real-time PCR, immunohistochemical, and western blot were performed. RESULTS: JuB pretreatment reversed APAP-induced CYP2E1 accumulations and alleviated APAP-induced acute liver injury. Furthermore, JuB treatment significantly inhibited oxidative stress and the pro-inflammatory cytokines, as well as alleviated hepatocyte apoptosis induced by APAP. Besides, our result also demonstrated that JuB treatment upregulated the levels of total Nrf2, facilitated its nuclear translocation, upregulated the expression of HO-1 and NQO-1, and inhibited the APAP-induced STING pathway activation. Finally, we verified that the beneficial effects of JuB were weakened by DMXAA and ML385. CONCLUSION: Our study suggested that JuB could ameliorate APAP-induced hepatic damage and verified a previously unrecognized mechanism by which JuB prevented APAP-induced hepatotoxicity through adjusting the Nrf2-STING pathway.

[Effects of transcutaneous electrical acupoint stimulation at different times assisted general anesthesia on stress response of patients undergoing open posterior lumbar surgery].

OBJECTIVE: To observe the effects of transcutaneous electrical acupoint stimulation (TEAS) at different times on the stress response during anesthesia and operation in the patients undergoing open posterior lumbar surgery. METHODS: A total of 94 patients undergoing open posterior lumbar surgery were randomly assigned to preoperative TEAS group(32 cases), intraoperative TEAS group(31 cases) and sham-TEAS group(31 cases). The same anesthetic method was used in the patients of 3 groups. Four electrodes were attached to the bilateral Hegu (LI4) and Neiguan (PC6) and connected to the electronic acupuncture instrument when patients entered the operation room. In the preoperative TEAS group, the patients received TEAS (10 to 20 mA) for 30 min before the anesthetic induction. TEAS (15 mA) was provided immediately when the operation starts till the end of ope-ration for the patients of the intraoperative TEAS group. In the sham-TEAS group, the electronic acupuncture instrument was switched on during the whole procedure of operation, but no electric current was output. Separately, at the moment of entering the operation room (T0), before endotracheal intubation (T1), at the time of endotracheal intubation (T2), 10 min after skin resection (T3), at the end of surgery (T4), recovery from anesthesia (T5) and at the time of extubation (T6), the heart rate (HR) and mean arterial pressure (MAP) were recorded. Using ELISA, the concentrations of epinephrine (E), norepinephrine (NE), dopamine (DA), cortisol (Cor) in serum were assayed at T0, T3, and T4; and blood glucose was tested with blood sugar paper at the same time points. RESULTS: Compared with T0 of the same group, HR was increased at T2 and decreased at T3 of the patients in the sham-TEAS group and the intraoperative TEAS group (P<0.05). Compared with the sham-TEAS group at the same time points, HR was decreased at T2 and increased at T3 of the patients in the preoperative TEAS group (P<0.05), and it was decreased at T6 of patients in the intraoperation TEAS group (P<0.05). HR was reduced at T2 in the preoperative TEAS group when compared with the intraoperative TEAS group. Compared with T0 of the same group, MAP was elevated at T2 and reduced at T3 and T4 in the sham-TEAS group (P<0.05); it decreased at T3, T4 and T5 in the preoperative TEAS group (P<0.05); it rose at T2 and was reduced at T3, T4 and T5 in the intraoperative TEAS group (P<0.05). When compared with the sham-TEAS group at the same time points, MAP decreased at T2 in the preoperative TEAS group (P<0.05), and at T6 in the intraoperative TEAS group (P<0.05). MAP was reduced at T2 and elevated at T6 in the preoperative TEAS group in comparison with the intraoperative TEAS group (P<0.05) at the same time points. Compared with T0 of the same group, the contents of E was increased at T3 in the sham-TEAS group and the intraoperative TEAS group (P<0.05); it was increased in all of the three groups at T4 (P<0.05); the contents of NE, DA, Cor and the blood glucose were increased at T4 in the sham-TEAS group (P<0.05). Compared with the sham-TEAS group at the same time points, the contents of E, DA at T3 and T4 and Cor at T3 in serum of the preoperative TEAS group were decreased (P<0.05); and the contents of E, NE, DA and Cor at T4 in the intraoperative TEAS group were decreased (P<0.05). CONCLUSION: TEAS-assisted general anesthesia can better maintain the stability of HR and MAP during anesthesia and operation in patients undergoing open posterior lumbar surgery, and reduce surgical stress response.

Transfer Behaviors of 30 Pesticide Residues during the Common Processing of Ginseng.

To reduce safety issues of ginseng products caused by excessive pesticide levels, this paper systematically elucidates the transfer rules of pesticides during processing by calculating the transfer rates and processing factors (PFs). The common methods of ginseng processing (water extraction, alcohol extraction, concentration, water extraction and alcohol precipitation, vacuum drying, freeze drying, spray drying) and 30 pesticides frequently occurring in ginseng were used as research objects. The results indicate that the pesticide residues in alcohol extract are much higher than those in water extract. During water extraction and alcohol precipitation, 93.2% of pesticides are transferred to the upper ethanol solution. Besides, drying could reduce the total amount but increase the concentration of pesticide residues. Water extraction-concentration-spray drying (PF ranges from 0.01 to 0.36) and alcohol extraction-concentration-vacuum drying (PF ranges from 1.10 to 3.70) are the processing methods with the lowest and highest pesticide processing factors, respectively.

Development of a UPLC-MS/MS method for the determination of active ingredients of Shuang Hu in rat blood and its application in pharmacokinetics.

A simple and sensitive method using in vivo microdialysis coupled with UPLC-MS/MS was established to evaluate the pharmacokinetics of Shuang Hu tincture (SHZTN). Xevo TQ-S was used to analyze the active ingredients of mesaconitine, hypaconitine, 4-hydroxycinnamic acid, ferulic acid and N-(2, 3-dimethyl phenyl)-2- aminobenzoic acid of SHZTN. Samples were prepared using a methanol precipitation method and the internal standards lannaconitine and p-hydroxybenzoic acid were added. The method validation was conducted according to the guidelines of the Pharmacopoeia of China. A good linear range was obtained in the range of 1-2,000 ng/ml. The intra-day and inter-day precisions were less than 14.7%, and the accuracy range of all the analytes was -10.5-9.3%. The recovery of each analyte was over 95.5%, and matrix effects can be neglected. After a single dose of 20 mg/kg SHZTN, the area under the curve and peak concentration of the five active ingredients were significantly increased by transdermal compared with oral administration, which indicated the high bioavailability of SHZTN. The time to peak concentration of all compounds was <3.4 h, and the half-life was <15.4 h, which indicated that the five compounds have the best absorption and rapid elimination. The method was successfully developed and applied to the pharmacokinetic study of SHZTN.

Trace heavy metals and harmful elements in roots and rhizomes of herbs: Screening level analysis and health risk assessment.

Objective: Heavy metal and harmful element contamination are frequently reported in Chinese herbal medicines (CHMs), and roots and rhizomes parts showed a higher content than other parts. To investigate the residue level and assess the potential human health risk of heavy metals and harmful elements in roots and rhizomes, 720 batches of the sample representing 20 species of herbs from different sources were collected. Methods: The content of Pb, Cd, As, Hg, and Cu in the digests was determined using ICP-MS. The chronic hazard index estimate based on non-cancer hazard quotient (HQ) was applied for potential health risk assessment of Pb, Cd, As, Hg, and Cu via consumption of CHMs. Results: Compared with the Chinese limit standard (Chinese Pharmacopoeia Commission, 2020 edition) of Pb, Cd, As, Hg, and Cu in Ginseng Radix et Rhizoma, the exceedance percentage of Pb in total samples was 14.1%, which were generally far higher than Cd, As, Hg, and Cu. Health risk assessment results based on hazard quotient calculating showed that total HQ of Cu, Pb, As, Cd, and Hg in Pulsatillae Radix and Clematidis Radix et Rhizoma exceeded 1, with the value of 1.543 and 1.235. Besides, Arsenic had the highest HQ value (0.957) in Pulsatillae Radix . Conclusion: Consuming raw materials of Pulsatillae Radix and Clematidis Radix et Rhizoma may pose a potential risk and Arsenic residues in Pulsatillae Radix deserved special attention.

Phillygenin from Forsythia suspensa leaves exhibits analgesic potential and anti-inflammatory activity in carrageenan-induced paw edema in mice.

Forsythia suspensa (Thunb.) Vahl (Oleaceae) leaves are valuable sources of phillygenin. This study aimed to isolate phillygenin from F. suspensa leaves and examine its analgesic and anti-inflammatory effects. Phillygenin was successfully extracted and isolated from F. suspensa leaves after fermentation. Phillygenin significantly reduced the number of writhing induced by acetic acid, prolonged the latency period in the hot plate test, and inhibited the xylene-induced ear edema and carrageenan-induced paw edema in mice. IL-6, TNF-α, IL-1ß, NO, and PGE2 levels in the carrageenan-induced paw edema were notably reduced after pretreatment with phillygenin. Phillygenin significantly decreased the iNOS and COX-2 protein expressions and the IκB-α and NF-κB p65 phosphorylation. This study demonstrated that phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders. The study contributes to the comprehensive development and utilization of F. suspensa leaves for economic and health care. PRACTICAL APPLICATIONS: Phillygenin is one of the major active ingredients in Forsythia suspensa. But the content of phillygenin in F. suspensa is very low which limits its application. Phillygenin has potential pharmacological activity and anti-inflammatory properties. However, the potential effects of phillygenin on analgesic activity have not been clarified. Furthermore, the data on its anti-inflammatory activity in vivo are relatively limited. This study evaluated the analgesic activity for the first time and the acute anti-inflammatory effect of phillygenin from F. suspensa leaves by fermentation, which indicated phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders.

Identification of Andrographis Herba and its common products using mini-barcode.

Andrographis Herba, the aerial part of Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae), has a wide geographic distribution and has been used for the treatment of fever, cold, inflammation, and other infectious diseases. In markets, sellers and buyers commonly inadvertently confuse with related species. In addition, most Chinese medicinal herbs are subjected to traditional processing procedures, such as steaming and boiling, before they are sold at dispensaries; therefore, it is very difficult to identify Andrographis Herba when it is processed into Chinese medicines. The identification of species and processed medicinal materials is a growing issue in the marketplace. However, conventional methods of identification have limitations, while DNA barcoding has received considerable attention as a new potential means to identify species and processed medicinal materials. In this study, 17 standard reference materials of A. paniculata, 2 standard decoctions, 27 commercial products and two adulterants were collected. Based on the ITS2 sequence, it could successfully identify A. paniculata and adulterants. Moreover, a nucleotide signature consisting of 71 bp was designed, this sequence is highly conserved and specific within A. paniculata while divergent among other species. Then, we used these new primers to amplify the nucleotide signature region from processed materials. In conclusion, the DNA barcoding method developed in the present study for authenticating A. paniculata is rapid and cost-effective. It can be used in the future to guarantee the quality of Andrographis Herba of each regulatory link for clinical use.

[Efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia].

OBJECTIVE: To observe the clinical efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia. METHODS: Fifty patients with asthenospermia and teratospermia meeting the inclusion criteria were randomly divided into a blank control (n = 10) and a medication group (n = 40), the former provided with fertility guidance and the latter treated with Jujing Decoction combined with lipoic acid. After 12 weeks of treatment, the clinical therapeutic effects were evaluated by comparing the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically abnormal sperm (MAS), rate of acrosome integrity, sperm DNA fragment index (DFI) and pregnancy rate between the two groups. RESULTS: Compared with the control group, the medication group achieved a significantly higher overall effectiveness rate (10% ï¼»1/10ï¼½ vs 88.89% ï¼»32/36ï¼½, P < 0.05) and pregnancy rate (0% ï¼»0/10ï¼½ vs 8.33% ï¼»3/36ï¼½, P < 0.05) after treatment. The medication group also showed remarkably increased PMS from (21.04 ± 6.49)% to (32.66 ± 7.05)%, decreased MAS from (98.31 ± 1.28)% to (96.52 ± 1.11)%, elevated acrosome integrity from (42.18 ± 16.67)% to (60.42 ± 11.61)%, and reduced sperm DFI from (21.92 ± 6.96)% to (12.37 ± 3.79)%, all with statistically significant differences compared with the blank control group. CONCLUSION: Jujing Decoction combined with lipoic acid can significantly improve sperm motility, reduce MAS and DFI and increase the pregnancy rate through antioxidant stress, and has a high clinical safety.

[Correlations between resting-state brain functional characteristics and TCM syndrome in premature ejaculation patients with heart-kidney disharmony].

OBJECTIVE: To investigate the correlation between the characteristics of resting-state brain function and the types of traditional Chinese medicine (TCM) syndrome in premature ejaculation (PE) patients with heart-kidney disharmony, and the pathogenesis of abnormal ejaculation of the patients. METHODS: We enrolled 33 PE patients with heart-kidney disharmony and 32 healthy controls matched in general demographic data, evaluated the severity of the main and concurrent symptoms of PE using the PE Diagnostic Tool (PEDT) and TCM Syndrome Scale (TCMSS), and obtained the brain structural and functional MRI data. We processed the collected data and calculated the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF) and regional homogeneity (Reho) of the brain with the DPABI software. Using the REST software package, we compared the significantly different brain areas between the PE and control groups by two-sample t-test and corrected the results for multiple comparisons by AlphaSim, followed by Pearson correlation analysis of ALFF, fALFF and Reho in abnormal brain areas and the PEDT and CMSS scores of the patients. RESULTS: The PE patients showed decreased ALFF values in the bilateral inferior temporal gyrus, left middle frontal gyrus and left orbital part of the inferior frontal gyrus, and increased ALFF values in the bilateral hippocampus, thalamus and precuneus, right inferior occipital gyrus, right calcarine and left inferior parietal, with positive correlations of the ALFF values of the left thalamus with the scores on PEDT (r = 0.35, P < 0.05) and TCMSS (r = 0.44, P < 0.05). The fALFF values of the patients were also decreased in the left temporal pole of the middle temporal gyrus and left anterior cingulate gyrus, but increased in the left inferior temporal gyrus. The Reho values of the patients were decreased as well in the right inferior temporal gyrus, left middle frontal gyrus, right dorsolateral superior frontal gyrus, right middle occipital gyrus, right middle occipital gyrus and right precuneus, but increased in the left temporal pole of the middle temporal gyrus, left middle frontal gyrus and left superior frontal gyrus, with negative correlations between the Reho value of the right superior parietal gyrus and TCMSS scores (r = －0.35, P < 0.05). CONCLUSION: Abnormal brain regions were found in PE patients with heart-kidney disharmony, with might be the pathologically associated with PE symptoms and heart-kidney disharmony of the patients.

Advances in locoregional therapy for hepatocellular carcinoma combined with immunotherapy and targeted therapy.

Locoregional therapies (LRTs) of hepatocellular carcinoma (HCC) represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC. Among these, TACE is used throughout the stage Ib to IIIb of HCC treatment. In recent years, immunotherapy led by immune checkpoint inhibitors has become a hot direction in clinical research. At the same time, targeted drugs such as Sorafenib and Apatinib have played an important role in the treatment and complementary therapy of advanced HCC, and their clinical application has been quite mature. HCC is the sixth most common malignant tumor in the world. When it comes to its treatment, different therapies have different indications, and their individual efficacies are not satisfactory, which makes the exploration of the use of combination therapy in HCC treatment become a new trend. In this paper, the status of the three therapies and the progress of their combined application are briefly reviewed.

Efficacy of erzhu jiedu recipe on hepatitis B cirrhosis with hyperalphafetoproteinemia: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Hepatitis B cirrhosis with hyperalphafetoproteinemia is the intermediate stage of liver cirrhosis progressing to hepatocellular carcinoma (HCC), there is no effective way to treat precancerous lesions of liver in modern medicine. In recent decades, clinical and experimental evidence shows that Chinese medicine (CM) has a certain beneficial effect on Hepatitis B Cirrhosis. Therefore, this trial aims to evaluate the efficacy and safety of a CM erzhu jiedu recipe (EZJDR) for the treatment of Hepatitis B Cirrhosis with Hyperalphafetoproteinemia. METHODS: We designed a randomized, double blind, placebo-controlled clinical trial. A total of 72 patients of Hepatitis B Cirrhosis with hyperalphafetoproteinemia were randomized in 2 parallel groups. Patients in the control group received placebo granules similar to the EZJDR. In the EZJDR group, patients received EZJDR twice a day, after meals, for 48 weeks. The primary efficacy measures were changes in serum alpha-fetoprotein (AFP) and alpha-fetoprotein alloplasm (AFP-L3); The secondary indicators of efficacy are changes in liver function indicators, HBV-DNA level; Liver stiffness measurement (LSM); Hepatic portal vein diameter; T lymphocyte subgroup indexes during treatment. All data will be recorded in case report forms and analyzed by Statistical Analysis System software. Adverse events will also be evaluated. RESULTS: The results showed that EZJDR can significantly inhibit the levels of AFP and AFP-L3 in patients with hepatitis B cirrhosis and hyperalphafetoproteinemia and have good security. ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Ethics Committee of Shuguang Hospital, affiliated with University of Traditional Chinese Medicine, Shanghai (NO.2018-579-08-01). TRIAL REGISTRATION: This trial was registered on Chinese Clinical Trial Center (NO.ChiCTR1800017165).

[Research progress on mechanism of phytohormones in regulating flavonoid metabolism].

Phytohormones play an important role at all stages of plant growth, influencing plant growth and development and regulating plant secondary metabolism, such as the synthesis of flavone, flavonol, anthocyanin, and other flavonoids. Flavonoids, a group of important secondary metabolites ubiquitous in plants, have antioxidative, anti-microbial, and anti-inflammatory activities and thus have a wide range of potential applications in Chinese medicine and food nutrition. With the development of biotechnology, phytohormones' regulation on flavonoids has become a research focus in recent years. This study reviewed the research progress on the mechanism of common phytohormones, such as abscisic acid, gibberellin, methyl jasmonate, and salicylic acid, in regulating flavonoid metabolism, and discussed the molecular mechanism of the synthesis and accumulation of flavonoids, aiming at clarifying the key role of phytohormones in modulating flavonoid metabolism. The result is of guiding significance for improving the content of flavonoids in plants through rational use of phytohormones and of reference value for exploring the mechanism of hormones in regulating flavonoid metabolism.

A Review on Phytochemicals of the Genus Maytenus and Their Bioactive Studies.

The genus Maytenus is a member of the Celastraceae family, of which several species have long been used in traditional medicine. Between 1976 and 2021, nearly 270 new compounds have been isolated and elucidated from the genus Maytenus. Among these, maytansine and its homologues are extremely rare in nature. Owing to its unique skeleton and remarkable bioactivities, maytansine has attracted many synthetic endeavors in order to construct its core structure. In this paper, the current status of the past 45 years of research on Maytenus, with respect to its chemical and biological activities are discussed. The chemical research includes its structural classification into triterpenoids, sesquiterpenes and alkaloids, along with several chemical synthesis methods of maytansine or maytansine fragments. The biological activity research includes activities, such as anti-tumor, anti-bacterial and anti-inflammatory activities, as well as HIV inhibition, which can provide a theoretical basis for the better development and utilization of the Maytenus.

Effects of phosphorus fertilizer on root characteristics, uptake and utilization of phosphorus and yield of dryland wheat with contrasting yearly rainfall pattern.

To understand the growth responses of dryland wheat to different application rates of phosphorus fertilizer in different rainfall years, we examined root characteristics, spike number, yield and phosphate utilization. Results would help improve phosphate fertilizer use in dryland wheat production. We carried out a field experiment at the research station of Shanxi Agricultural University from 2012 to 2016. We examined the effects of four application rates of phosphorus (0, 75, 150 and 225 kg·hm-2 on root growth, phosphate utilization and yield formation of dryland wheat in different years with contrasting rainfall pattern. Compared with the treatment without phosphorus fertilization, phosphate application increased root surface area at all growth stages and root weight density in the 0-80 cm soil layer at jointing, anthesis, and maturity stages. Phosphate application significantly increased soil water consumption from jointing to anthesis, and total soil water consumption in the growing season. Phosphate application enhanced the amount of pre-anthesis phosphate translocation and phosphate accumulation of grain. Spike number, yield and water use efficiency were increased with 75, 150 and 225 kg P·hm-2 by 9.2% to 22.5%, 11.8% to 30.0%, and 2.1% to 12.1%, respectively. In the dry years, the application rates of 150 and 225 kg P·hm-2 in comparison to 75 kg P·hm-2 significantly increased root weight density and root surface area at all stages, soil water consumption from sowing to jointing and from jointing to anthesis, and total water consumption in the growing season. In comparison to the rate of 75 kg P·hm-2, 150 and 225 kg P·hm-2 increased soil water consumption from sowing to jointing by 7.3-8.7 mm, soil water consumption from jointing to anthesis by 15.6-18.1 mm, and total water consumption by 15.6-18.1 mm. Significant increase in the pre-anthesis phosphate translocation and phosphate accumulation in grain was higher under 150 and 225 kg P·hm-2 than that under 75 kg P·hm-2 in dry years. Furthermore, the two rates (150 and 225 kg P·hm-2) in dry years increased spike number by 9.3%-10.7% and yield by 11.9%-14.6%. The application rate of 150 kg P·hm-2 significantly improved phosphorus use efficiency by 20%-82% in comparison to other rates. In normal years, the rates of 150 and 225 kg P·hm-2 increased root surface area, root weight density at both anthesis and maturity compared with 75 kg P·hm-2. Soil water consumption from anthesis to maturity and total soil water consumption in the growing season were also increased by 1.2-15.0 and 3.8-23.1 mm, respectively. In addition, phosphorus accumulation in post-anthesis and phosphate accumulation in grain were increased in both 150 and 225 kg P·hm-2, which increased spike number by 1.4%-9.6% and yield by 3.5%-10.4%. The effects of phosphate application at the rate of 150 kg P·hm-2 were significantly different from 75 and 225 kg P·hm-2. In conclusion, phosphorus fertilizer application enhanced uptake of water and phosphate in dryland wheat at early and middle growth stages in dry years and at the late growth stage in normal years. Phosphorus application increased wheat yield mainly due to the increases of spike number. The application of 150 kg P·hm-2 is the best choice for high water and phosphorus fertilizer use efficiency and high yield in both dry and normal years.

A novel palmitic acid hydroxy stearic acid (5-PAHSA) plays a neuroprotective role by inhibiting phosphorylation of the m-TOR-ULK1 pathway and regulating autophagy.

AIMS: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic-related neurodegeneration. The aim of the present study was to investigate whether 5-PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to autophagy. METHODS: 5-PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a range of inflammatory factors. RESULTS: Although there was no significant improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL decreased significantly following the administration of 5-PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5-PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms of apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5-PAHSA. CONCLUSION: We found that 5-PAHSA can enhance autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice.