Waterlogging in soil restricts the growth of Gleditsia sinensis seedlings and inhibits the accumulation of lignans and phenolic acids in thorns.

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.

[Analysis on Driving Factors, Reduction Potential, and Environmental Effect of Inorganic Fertilizer Input in Chongqing].

In this study, we sought to quantify the effect of planting structure change on fertilizer input and environmental cost in Chongqing and develop scientific and rational strategies for chemical fertilizer reduction. Based on the crop fertilizer quota standard and large sample farmer survey data under the medium productivity level in Chongqing, we evaluated and analyzed the application reduction potential and environmental benefits of fertilizer with the difference method and life cycle assessment. The results showed that:① since Chongqing became a municipality directly under the central government (1997), Chongqing crop planting structure had greatly changed, and the proportion of food crop (rice, corn, wheat, bean, and potato) decreased by 21%. The area of fruits and vegetables increased from 3.36×105 hm2 to 1.05×106 hm2, and their proportion increased by 20%. ② Nearly 55% of fertilizers had been consumed by vegetable (37%) and citrus production systems, and 11%, 12%, and 12% of fertilizers were consumed by rice, corn, and potato, respectively. ③ The total fertilizer reduction of the Chongqing planting industry could reach up to 1.69×105 tons during the period of "the 14th Five-Year Plan," with a fertilizer reduction potential of 18.6%. The fertilizer reduction potential (reduction amount) of rice, corn, citrus, and vegetables would reach 0.3% (2.9×102 tons), 12% (1.45×104 tons), 21% (3.65×104 tons), and 30% (1.18×105 tons), respectively. On the other hand, the rape system was insufficient in phosphorus potassium fertilizers, and the corn tended to be insufficient in potash fertilizer. ④ The current production level was low, and the nitrogen loss, greenhouse gas emissions, and eutrophication potential in the planting industry of Chongqing reached 1.81×105 tons (N), 1.43×107 tons (CO2-eq), and 1.74×105 tons (PO4-eq). With the increase in the realization degree of the crop quota standard (60%-100%), the reactive nitrogen loss, greenhouse gas emissions, and eutrophication potential decreased by 14.9%-24.9%, 10.1%-16.7%, and 13.8%-23%, respectively. The structure of the planting industry in Chongqing significantly changed, the total fertilizer consumption in Chongqing tended to decline gradually, and the fertilization intensity of commercial crops stayed at a high level. The agricultural fertilizer reduction potential and the reactive nitrogen and greenhouse gas emission reduction potential were large, especially for citrus and vegetable production systems. However, it is also necessary to pay attention to insufficient corn potash fertilizer and rape phosphorus potassium fertilizer investment and carry out collaborative promotion of fertilizer reduction.

Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism.

OBJECTIVE: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. METHODS: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. RESULTS: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. CONCLUSION: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.

[Progress in antitumor activity of diterpenoid alkaloids in plants of Aconitum].

Small-molecule compounds with rich sources have diverse structures and activities. The active ingredients in traditional Chinese medicine(TCM) provide new sources for the discovery of new antitumor drugs. Aconitum plants as Chinese medicinal plants have the effects of dispelling wind, removing dampness, warming meridian, and relieving pain. They are mainly used to treat inflammation, pain, rheumatism, and tumors, improve heart function, and dilate blood vessels in clinical practice. Diterpenoid alkaloids are the main active components of Aconitum plants, including C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids. Stu-dies have demonstrated that diterpenoid alkaloids can effectively treat lung cancer, liver cancer, breast cancer, colon cancer and other cancers. Diterpenoid alkaloids are considered as the most promising natural compounds against cancers. In this review, we summarized the chemical structures and antitumor activities of C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids extracted from plants of Aconitum, aiming to provide reference for further development of diterpenoid alkaloids from Aconitum as antitumor drugs.

[Effects of acupuncture on hemorrhagic transformation and motor function in stroke patients after intravenous thrombolysis with rt-PA: a prospective cohort study].

OBJECTIVE: To observe the effects of the Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on hemorrhagic transformation and limb motor function after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in stroke patients. METHODS: A total of 130 stroke patients after rt-PA thrombolytic were divided into an acupuncture group (58 cases, 1 case dropped off) and a non-acupuncture group (72 cases, 7 cases dropped off) according to whether they received acupuncture treatment. Propensity score matching (PSM) was used to match each group, with 38 patients in each group. The patients in the non-acupuncture group received rt-PA thrombolytic therapy and western medical basic treatment. In addition to the basic treatment, the patients in the acupuncture group received Xingnao Kaiqiao acupuncture at Shuigou (GV 26), bilateral Neiguan (PC 6), and ipsilateral Sanyinjiao (SP 6), Chize (LU 5), once a day for 14 days. The incidence of hemorrhagic transformation within 30 days after onset was compared between the two groups. The Fugl-Meyer assessment (FMA) score and activities of daily living (ADL) score were observed at baseline and 30 days, 6 months, 1 year after onset in the two groups. The disability rate at 6 months and 1 year after onset was recorded, and safety was evaluated in both groups. RESULTS: The incidence of hemorrhagic transformation in the acupuncture group was 5.3% (2/38), which was lower than 21.1% (8/38) in the non-acupuncture group (P<0.05). At 30 days, 6 month, and 1 year after onset, the FMA and ADL scores of both groups were higher than those at baseline (P<0.01), and the scores in the acupuncture group were higher than those in the non-acupuncture group (P<0.01). The disability rate in the acupuncture group at 1 year after onset was 10.5% (4/38), which was lower than 28.9% (11/38) in the non-acupuncture group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). CONCLUSION: The Xingnao Kaiqiao acupuncture method could reduce the incidence of hemorrhagic transformation in stroke patients after intravenous thrombolysis with rt-PA, improve their motor function and daily living ability, and reduce the long-term disability rate.

Virtual screening-molecular docking-activity evaluation of Ailanthus altissima (Mill.) swingle bark in the treatment of ulcerative colitis.

BACKGROUND: The dried bark of Ailanthus altissima (Mill.) Swingle is widely used in traditional Chinese medicine for the treatment of ulcerative colitis. The objective of this study was to explore the therapeutic basis of the dried bark of Ailanthus altissima (Mill.) Swingle for the treatment of ulcerative colitis based on Virtual Screening-Molecular Docking-Activity Evaluation technology. METHODS: By searching the Traditional Chinese Medicine Systems Pharmacology TCMSP Database and Analysis Platform, 89 compounds were obtained from the chemical components of the dried bark of Ailanthus altissima (Mill.) Swingle. Then, after preliminarily screening the compounds based on Lipinski's rule of five and other relevant conditions, the AutoDock Vina molecular docking software was used to evaluate the affinity of the compounds to ulcerative colitis-related target proteins and their binding modes through use of the scoring function to identify the best candidate compounds. Further verification of the compound's properties was achieved through in vitro experiments. RESULTS: Twenty-two compounds obtained from the secondary screening were molecularly docked with ulcerative colitis-related target proteins (IL-1R, TLR, EGFR, TGFR, and Wnt) using AutoDock Vina. The free energies of the highest scoring compounds binding to the active cavity of human IL-1R, TLR, EGFR, TGFR, and Wnt proteins were - 8.7, - 8.0, - 9.2, - 7.7, and - 8.5 kcal/mol, respectively. The potential compounds, dehydrocrebanine, ailanthone, and kaempferol, were obtained through scoring function and docking mode analysis. Furthermore, the potential compound ailanthone (1, 3, and 10 µM) was found to have no significant effect on cell proliferation, though at 10 µM it reduced the level of pro-inflammatory factors caused by lipopolysaccharide. CONCLUSION: Among the active components of the dried bark of Ailanthus altissima (Mill.) Swingle, ailanthone plays a major role in its anti-inflammatory properties. The present study shows that ailanthone has advantages in cell proliferation and in inhibiting of inflammation, but further animal research is needed to confirm its pharmaceutical potential.

Treatment of polycystic ovary syndrome and its associated psychiatric symptoms with the Mongolian medicine Nuangong Qiwei Pill and macelignan.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mongolian medicine Nuangong Qiwei Pill (NGQW) is a folk prescription with a long history of use by the Mongolian people. NGQW comprises seven Mongolian medicines, which have the effects of regulating and nourishing blood, warming the uterus, dispelling cold and relieving pain. For a long time, it has been used as a good remedy for gynecological diseases, with remarkable curative effects, favored by the majority of patients and recommended by doctors. Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder that can lead to menstrual disorders or infertility. In the gynecological classification of Mongolian medicine, polycystic ovary syndrome has not been distinguished in detail, and the mechanism of NGQW in the treatment of polycystic ovary syndrome has not been scientifically studied and standardized. AIM OF THE STUDY: The aim of this study was to clarify the mechanism of action of NGQW and macelignan in the treatment of PCOS and to provide a reference for the clinical application of these drugs. MATERIALS AND METHODS: The effect of intragastric administration of NGQW and macelignan on PCOS model mice was observed. The mental status of mice was examined behaviorally, and serum hormone levels and oxidative stress parameters were measured by ELISA. Giemsa staining was used to detect the reproductive cycle, and HE staining was used to observe the ovarian status. Immunofluorescence staining was performed to observe the proliferation and apoptosis of ovarian granulosa cells. qRT‒PCR was conducted to measure the expression of IL-6, BAX, BCL-2, and estrogen synthesis-related genes in ovarian tissue and particle cells. RESULTS: In the dehydroepiandrosterone (DHEA)-induced PCOS model mice, both NGQW and macelignan improved the estrous cycle; increased the estradiol (E2) content; lowered testosterone (T), progesterone (P) and luteinizing hormone (LH) levels; reduced the number of polycystic follicles; promoted granulosa cell proliferation; reduced granulosa cell apoptosis; and alleviated depression and anxiety. In addition, Nuangong Qiwei Pill and macelignan reduced the mRNA levels of the ovarian inflammatory factor IL-6; improved the disordered levels of the antioxidant indicators GSH, MDA, and SOD; and activated the TGF-ß3 signaling pathway to increase the transcription of Cyp19a1, which increases estrogen secretion. CONCLUSION: NGQW and macelignan can treat PCOS through the TGF-ß3/Smad/Cyp19a1 signaling pathway to regulate the secretion ability of ovarian granulosa cells. Our research justifies the traditional use of NGQW to treat PCOS and enriches the scope of action of macelignan.

[Research advance on structure and function of amides in Zanthoxylum plants].

Zanthoxylum belongs to the Rutaceae family, and there are 81 Zanthoxylum species and 36 varieties in China. Most of the Zanthoxylum plants are used as culinary spice. In recent years, scholars in China and abroad have carried out in-depth research on Zanthoxylum plants, and found that the peculiar numbing sensation of Zanthoxylum plants originates from amides. It is also determined that amides are an important material basis for exerting pharmacological effects, especially in anti-inflammatory analgesia, anesthesia and other aspects. In this paper, 123 amides in 26 Zanthoxylum plants and their pharmacological activity that have been reported were summarized, which provided scientific reference for the clinical application of Zanthoxylum plants and the research and development of new drugs, and also facilitated the sustainable development and utilization of Zanthoxylum plant resources.

Oxepine-containing pyrazinopyrimidine alkaloids and quinolinone derivatives produced by Aspergillus versicolor AS-212, a deep-sea-derived endozoic fungus.

Four new oxepine-containing pyrazinopyrimidine alkaloids, versicoxepines A - D (1-4), two quinolinone alkaloid analogs including 3-hydroxy-6-methoxy-4-phenylquinolin-2(1H)-one (5) and 3-methoxy-6-hydroxy-4-phenylquinolin-2(1H)-one (6) which were new naturally occurring compounds, together with two known compounds (7 and 8) were isolated from Aspergillus versicolor AS-212, an endozoic fungus isolated from the deep-sea coral Hemicorallium cf. imperiale, which was collected from the Magellan Seamounts in the Western Pacific Ocean. Their structures were determined by extensive analysis of the spectroscopic and X-ray crystallographic data as well as by chiral HPLC analysis, ECD calculation, and DP4+ probability prediction. Structurally, versicoxepines B and C (2 and 3) represent the first example of a new oxepine-containing pyrazinopyrimidine alkaloid whose cyclic dipeptide moiety is composed of the same type of amino acid (Val or Ile). Compound 5 displayed antibacterial activity against aquatic pathogens, Vibrio harveyi and V. alginolyticus, with MICs of 8 µg/mL.

Alkylamides from Zanthoxylum armatum DC. and their neuroprotective activity.

Zanthoxylum armatum DC. is an important medicinal plant, and its pericarps are commonly used as a natural spice in Asian countries. In this study, fifteen alkylamides were isolated and elucidated from the pericarps of Z. armatum, including five undescribed alkylamides (1-5) and ten known compounds (6-15). The molecular structures of all compounds were elucidated by 1D and 2D NMR spectroscopic analysis and mass spectrometry, among which the absolute configuration of compound 15 was determined by the Mo2(OAc)4-induced circular dichroism method. Moreover, all compounds were screened for their neuroprotective activity against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells for the evaluation of their neuroprotective activity. Especially, compounds 2-4 expressed potential neuroprotective activity, and further research showed that the cell viability was significantly enhanced in a concentration dependent manner when the cells were treated for 6 h. Moreover, compounds 2-4 could decrease reactive oxygen species accumulation. This paper enriched structure types of alkylamides in Zanthoxylum armatum.

Cancer Cell Membrane-Coated Gambogic Acid Nanoparticles for Effective Anticancer Vaccination by Activating Dendritic Cells.

Purpose: Recent studies have shown that traditional Chinese medicine (TCM), such as gambogic acid (GA), is involved in the regulation of tumor immune microenvironment and can be combined with other anti-tumor treatment strategies. Here, we used GA as an adjuvant to construct a nano-vaccine to improve the anti-tumor immune response of colorectal cancer (CRC). Materials and Methods: We used a previously reported two-step emulsification method to obtain poly (lactic-co-glycolic acid) /GA nanoparticles (PLGA/GA NPs), and then CT26 colon cancer cell membrane (CCM) was used to obtain CCM-PLGA/GA NPs. This novel nano-vaccine, CCM-PLGA/GA NPs, was co-synthesized with GA as an adjuvant and neoantigen provided by CT26 CCM. We further confirmed the stability, tumor targeting, and cytotoxicity of CCM-PLGA/GA NPs. The regulatory effect on the tumor immune microenvironment, the anti-tumor efficacy, and the combined anti-tumor efficacy with anti-PD-1 monoclonal Antibodies (mAbs) of this novel nano-vaccine was also detected in vivo. Results: We successfully constructed the CCM-PLGA/GA NPs. In vitro and in vivo tests showed low biological toxicity, as well as the high tumor-targeting ability of the CCM-PLGA/GA NPs. Besides, we revealed a remarkable effect of CCM-PLGA/GA NPs to activate the maturation of dendritic cells (DCs) and the formation of a positive anti-tumor immune microenvironment. Conclusion: This novel nano-vaccine constructed with GA as the adjuvant and CCM providing the tumor antigen can not only directly kill tumors by enhancing the ability of GA to target tumors, but also indirectly kill tumors by regulating tumor immune microenvironment, providing a new strategy for immunotherapy of CRC.

Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/ß-catenin signaling pathway and analysis of active ingredients by molecular docking.

Background: Sea buckthorn (SBT) is a traditional Chinese medicine (TCM), rich in calcium, phosphorus, and vitamins, which can potentially prevent and treat osteoporosis. However, no research has been conducted to confirm these hypotheses. QiangGuYin (QGY) is a TCM compound used to treat osteoporosis. There is a need to investigate whether SBT enhances QGY efficacy. Objectives: The aim of this study was to explore whether SBT enhances QGY efficacy by inhibiting CKIP-1 and Notum expression through the Wnt/ß-catenin pathway. The study also aimed to explore the active components of SBT. Methods: Experimental animals were divided into control, model, QGY, SBT, SBT + Eucommia ulmoides (EU), and SBT + QGY groups. After treatment, bone morphometric parameters, such as estrogen, PINP, and S-CTX levels, and Notum, CKIP-1, and ß-catenin expression were examined. Screening of SBT active components was conducted by molecular docking to obtain small molecules that bind Notum and CKIP-1. Results: The results showed that all the drug groups could elevate the estrogen, PINP, and S-CTX levels, improve femoral bone morphometric parameters, inhibit Notum and CKIP-1 expression, and promote ß-catenin expression. The effect of SBT + EU and SBT + QGY was superior to the others. Molecular docking identified that SBT contains seven small molecules (folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin) with potential effects on CKIP-1 and Notum. Conclusion: SBT improves bone morphometric performance in PMOP rats by inhibiting CKIP-1 and Notum expression, increasing estrogen levels, and activating the Wnt/ß-catenin signaling pathway. Furthermore, SBT enhances the properties of QGY. Folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin are the most likely active ingredients of SBT. These results provide insight into the pharmacological mechanisms of SBT in treating osteoporosis.

[The effects of different herbal compound and extracts from different extraction methods on hypoxia tolerance in mice].

Objective: To investigate the effects of different prescription compositions of traditional Chinese medicine and its different extraction methods of compound formula extracts on hypoxia tolerance in mice, in order to preferably select their prescription compositions and preparation extraction methods. Methods: Male BALB/c mice were randomly divided into 6 groups: blank control group, compound danshen group, compound Rhodiola Rosea alcohol-water extract group (Rhodiola rosea, Astragali Radix, Polygonati Rhizoma, Lycii Fructus), compound Rhodiola Rosea water extract group, compound Astragalus alcohol-water extract group (Astragali Radix, Polygonati Rhizoma, Lycii Fructus) and compound Astragalus water extract group, 30 mice in each group. Each group was administered continuously by gavage for 10 d. The blank group was gavaged with sterilized injection water. The mice in the other groups were treated with 0.15 g/kg of compound danshen, 3 g/kg of compound Rhodiola Rosea alcohol-water extract or water extract, and 1.7 g/kg of compound Astragalus alcohol-water extract or water extract, respectively. Each group was subjected to normobaric hypoxia tolerance test, sodium nitrite toxicity survival test and acute cerebral ischemia-hypoxia test 1 h after the last gavage, and the mice brain tissues were used to determine the activity of antioxidant enzymes and metabolites related to oxidative stress. Results: Compared with the blank control group, in normobaric hypoxia tolerance test, the survival time of mice in the compound danshen group and the compound Astragalus alcohol-water extract group and water extraction group was prolonged significantly (P＜0.01), and the number of open-mouth gasping after cerebral ischemia and hypoxia was increased significantly (P＜0.05). There was no statistical difference in survival time after sodium nitrite injection in each group. Compared with the blank control group, the activities of T-AOC, SOD, GSH and CAT were increased significantly (P＜0.05, P＜0.01) and the content of MDA was decreased significantly (P＜0.01) in the compound Astragalus water extract group. Compared with the compound danshen group, the activities of SOD, CAT and GSH were increased significantly (P＜0.01, P＜0.05) and the content of MDA was decreased significantly (P＜0.05). Conclusion: Compound Astragalus water extraction has the best effect of hypoxia tolerance, compound Rhodiola Rosea can eliminate Rhodiola rosea and consists of Astragali Radix, Polygonati Rhizoma, Lycii Fructus and its extraction method is water extraction.

Silver and copper-oxide nanoparticles prepared with GA3 induced defense in rice plants and caused mortalities to the brown planthopper, Nilaparvata lugens (Stål).

BACKGROUND: Nanoparticles have been employed as nanopesticides for pest control in agriculture. However, the harmful effects of their chemical synthesis on human and environmental health have resulted in increased use of green synthetic approaches, including the use of plant extracts. The brown planthopper, Nilaparvata lugens (Stål) (BPH), is a severe pest of rice plants (Oryza sativa L.), especially in Asia. It is usually controlled chemically but has developed resistance against many insecticides. RESULTS: In this study, we synthesized metallic silver (Ag-NPs) and copper-oxide (CuO-NPs) nanoparticles using the exogenous phytohormone, gibberellic acid (GA3), as a reducing agent. We then sprayed them separately on rice plants and BPH together and evaluated their effects on the plants and insects. SEM and TEM images showed that the synthesis was successful, indicated by the sizes (25-60 nm), uniform shape and spherical and cubical structures of Ag-NPs, as well as by the rugby sheet-like of CuO-NPs with lateral sizes of 150-340 nm and thickness of 30-70 nm. Independent applications of the nanoparticles and GA3 on rice plants induced different volatile profiles, of which the highest number emitted was under Ag-NPs, including the highest emission of linalool. Transcriptome analysis showed that Ag-NPs-treated rice plants showed different transcriptome profiles compared to the control, 24 h after treatment, including the upregulation of the linalool synthase gene, genes of plants transcription factors such as WRKY, bHLH and NAC and other genes involved in plant defense responses. In all treatments, the mortality rate of BPH increased with an increase in NPs concentrations over time but was prominent under Ag-NPs treatment. The LC50 values for Ag-NPs and CuO-NPs decreased with an increase in time. Also, the nanoparticles increased the activities of protective enzymes (POD, SOD and CAT), inhibited that of detoxification enzymes (A-CHE, ACP and AKP), and reduced total protein concentrations in the BPH. CONCLUSIONS: These results show that synthesizing nanoparticles using phytohormones may be a safer and environmentally friendly option, which also holds promise for controlling the BPH in rice production.

Factors Associated with the Magnitude Of acUpuncture treatment effectS (FAMOUS): a meta-epidemiological study of acupuncture randomised controlled trials.

OBJECTIVE: To identify factors and assess to what extent they impact the magnitude of the treatment effect of acupuncture therapies across therapeutic areas. DATA SOURCE: Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc, between 2015 and 2019. STUDY SELECTION: The inclusion criteria were trials with a total number of randomised patients larger than 100, at least one patient-important outcome and one of two sets of comparisons. DATA ANALYSIS: The potential independent variables were identified by reviewing relevant literature and consulting with experts. We conducted meta-regression analyses with standardised mean difference (SMD) as effect estimate for the dependent variable. The analyses included univariable meta-regression and multivariable meta-regression using a three-level robust mixed model. RESULTS: 1304 effect estimates from 584 acupuncture randomised controlled trials (RCTs) were analysed. The multivariable analyses contained 15 independent variables . In the multivariable analysis, the following produced larger treatment effects of large magnitude (>0.4): quality of life (difference of adjusted SMDs 0.51, 95% CI 0.24 to 0.77), or pain (0.48, 95% CI 0.27 to 0.69), or function (0.41, 95% CI 0.21 to 0.61) vs major events. The following produced larger treatment effects of moderate magnitude (0.2-0.4): single-centred vs multicentred RCTs (0.38, 95% CI 0.10 to 0.66); penetration acupuncture vs non-penetration types of acupuncture (0.34, 95% CI 0.15 to 0.53); non-pain symptoms vs major events (0.32, 95% CI 0.12 to 0.52). The following produced larger treatment effects of small magnitude (<0.2): high vs low frequency treatment sessions (0.19, 95% CI 0.03 to 0.35); pain vs non-pain symptoms (0.16, 95% CI 0.04 to 0.27); unreported vs reported funding (0.12, 95% CI 0 to 0.25). CONCLUSION: Patients, clinicians and policy-makers should consider penetrating over non-penetrating acupuncture and more frequent treatment sessions when feasible and acceptable. When designing future acupuncture RCTs, trialists should consider factors that impact acupuncture treatment effects.

[Ten-year Trend Analysis of Eutrophication Status and the Related Causes in Lake Hongze].

In order to propose pertinent suggestions regarding eutrophication control for Lake Hongze, we used monthly monitoring data from 2011 to 2020 to elucidate the spatiotemporal changing characteristics of eutrophic status and the relevant driving factors. As the main river entering Lake Hongze, River Huaihe experienced an increase in permanganate index and a decrease in TN in the last 10 years. Meanwhile, Secchi depth, TP, and permanganate index increased, whereas TN and Chl-a concentration decreased significantly in Lake Hongze. As a result, the eutrophic status TLI index of Lake Hongze declined over the past 10 years. The change trend of TLI in Lake Hongze differed spatially. As the main water passage of River Huaihe, the algal biomass was lower in the eastern region than that in the other two lake regions, regardless of the relatively high nutrient concentration, due to the short water retention time. Furthermore, the water quality of River Huaihe improved; thus, the TLI index decreased significantly in the eastern lake region. The northern region had a high coverage of aquatic vegetation, which not only reduced the concentration of water nutrients but also provided a habitat for zooplankton and fish, effectively inhibiting algal growth. Thus, the TLI index was lowest among the three lake areas and showed a downward trend over the last 10 years. In the western region, the algal biomass was the highest due to the intensification of phosphorus release from sediment in summer. Thus, the TLI index was the highest and had not improved in the past 10 years. There were also significant seasonal differences in the TLI of Lake Hongze, which was highest in summer, due to the relatively high algal biomass. Moreover, the algal biomass in summer was mainly affected by the concentration of nitrate. According to the spatiotemporal distribution characteristics of eutrophic status and the impacting factors in Lake Hongze, corresponding measures for eutrophication control should be taken for different seasons and lake areas.

Discovery of potent immune-modulating molecule taccaoside A against cancers from structures-active relationships of natural steroidal saponins.

BACKGROUND: In recent years, the T-cell therapy and immune checkpoint inhibitors toward CTLA-4 and PD-1/PD-L1 axis antibody therapy have acquired encouraging success. However, most of patients were still not benefited with lots of troubles, such as low penetration of tissues/cells, strong immunogenicity and cytokine release syndrome, and long manufacturing process and expensive costs. By contrast, the immune-modulating small molecules possessed natural advantages to overcome these obstacles and might achieve greater success. PURPOSE: Exploring the potent immune-modulating natural small molecules and revealing what kinds of molecules or structures with the immunomodulatory activity against cancers. METHODS: A novel non-cytotoxic T-cell immunomodulating screening model was used to identify the cytotoxic/selective/immunomodulatory bioactivity for 148 natural steroidal saponins. The structure-activity relationships (SARs) research was used to reveal the key groups for immunomodulation/cytotoxicity/selectivity. The negative selection was used to isolate and purify the T-cell. The cell viability assay was used to measure the anti-cancer effect in vitro. The ELISA assay was used to detect the cytokines for IL-1ß, IL-6, TNF-α, IFN-γ, IL-12, perforin and granzyme B (GZMB). The western blotting assay was used to research the immunomodulatory mechanism. The siRNA knockdown was used to generate the IFN-γ resistant melanoma cells. The NOG immune-deficient mice were used to evaluate the anti-tumor efficacy in vivo. The peripheral blood samples from 10 cancer patients were used to detect the broad population anti-tumor efficacy. RESULTS: It was reported that the correlation among structures and immunomodulation/ cytotoxicity/selectivity, in which opening ring-F with 26-O-glucopyranosyl, disaccharide and trisaccharide chains at C-3, steric hindrance and polarity of C-22 were key immunomodulatory groups. Moreover, taccaoside A was identified as the most potent candidate against cancer cells, including non-small cell lung cancer, triple negative breast cancer, and the IFN-γ resistant melanoma, partly through enhancing T lymphocyte mTORC1-Blimp-1 signal to secrete GZMB. Besides, 10 patients derived T-cell also would be modulated against cancer cells in vitro. Moreover, the overall survival was great extended (>140 days vs 93 days) with nearly 100% tumor burden disappearance (0 mm3vs 1006 ± 79.5 mm3) in mice. CONCLUSION: This work demonstrated one possibility for this concerned purpose, and identified a potent immune-modulating natural molecule taccaoside A, which might contribute to cancer immunotherapy in future.

Cellulose filter paper immobilized α-glucosidase and its application to screening inhibitors from traditional Chinese medicine.

In this study, α-glucosidase was successfully immobilized on cellulose filter paper and further applied to screening inhibitors from traditional Chinese medicines combined with capillary electrophoresis analysis. For α-glucosidase immobilization, a cellulose filter paper was used as the carrier and grafted with amino groups by coating chitosan, then α-glucosidase was covalently bonded on the amino-modified carrier via epoxy ring-opening reaction using polyethylene glycol diglycidyl ether as the crosslinker. Several parameters influencing the enzyme immobilization were optimized and the optimal values were enzyme concentration of 4 U/mL, polyethylene glycol diglycidyl ether concentration of 1.25%, chitosan concentration of 7.5 mg/mL, immobilization pH 7.0, crosslinking time of 4 h and immobilization time of 2 h. The immobilized α-glucosidase exhibited good batch-to-batch reproducibility (RSD = 2.1%, n = 5), excellent storage stability (73.5% of its initial activity after being stored at 4°C for 15 days), and reusability (75% of its initial activity after 10 repeated cycles). The Michaelis constant of immobilized α-glucosidase and half-maximal inhibitory concentration of acarbose were calculated to be 1.12 mM and 0.38 µM, respectively. Finally, the immobilized α-glucosidase was used for screening inhibitors from 14 kinds of Traditional Chinese Medicine extracts, and Sanguisorbae Radix showed the strongest inhibitory effect on α-glucosidase.

The natural compound from Garcinia bracteata mainly induces GSDME-mediated pyroptosis in esophageal cancer cells.

BACKGROUND: Pyroptosis, an inflammatory form of programmed cell death (PCD), is reported to play important roles in the treatment of tumors. In our previous studies, we found that neobractatin (NBT), a caged prenylxanthone isolated from edible fruits of Garcinia bracteata C. Y. Wu ex Y. H. Li, showed anticancer effects against different cancer cells. However, the effect of NBT on pyroptosis is not well understood. PURPOSE: This study aims to investigate whether and how GSDME-mediated pyroptosis contributes to NBT-induced antitumor effects in esophageal cancer (EC) cells. METHODS: Cell viability assay and colony formation assay were used to determine the anticancer effects of NBT in esophageal cancer cells. Lactate dehydrogenase (LDH) release assay and microscopy imaging were used to detect the main characteristic of pyroptosis. CRISPR-Cas9 knockout and siRNA knockdown were performed to verify the roles of GSDME and caspase-3 in NBT-induced pyroptosis. Flow cytometry was used to measure the reactive oxygen species (ROS) level and cell apoptosis. The changes of related protein level were detected by Western blot. Furthermore, animal experiments were used to verify the in vivo effect of NBT. RESULTS: The results showed that NBT reduced the viability of EC cells mainly through GSDME-mediated pyroptosis. Morphologically, NBT induced cell swelling and formed large bubbles emerging from plasma membrane in wild type EC cells. Furthermore, NBT induced the cleavage of GSDME by activating caspase-3 in EC cells. On the other hand, caspase-3 activated by NBT also induced apoptosis especially at high dosage. Knocking down GSDME switched NBT-induced cell death from mainly pyroptosis to apoptosis in vivo and in vitro. Mechanistic studies indicated that NBT led to accumulation of ROS, which then regulated the phosphorylation of both JNK and MEK/ERK. In the absence of ROS or caspase-3, NBT-induced pyroptosis and apoptosis were completely reversed. Moreover, NBT showed a significant antitumor effect in both the KYSE150 and GSDME knockout KYSE150-/- xenograft models by inducing pyroptosis and apoptosis, respectively. CONCLUSION: Our results indicated that natural compound NBT could induce GSDME-mediated pyroptosis and apoptosis in esophageal cancer cells, making it a potential therapeutic drug in clinical treatment.

Total alkaloid fraction of Leonurus japonicus Houtt. Promotes angiogenesis and wound healing through SRC/MEK/ERK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt., also known as motherwort, is a traditional Chinese medicine that was first identified in Shennong Bencao Jing, the first and essential pharmacy monograph in China. L. japonicus has been regarded as a good gynecological medicine since ancient times. It has been widely used in clinical settings for treatment of gynecological diseases and postnatal rehabilitation with good efficacy and low adverse effects. AIM OF THE STUDY: The main purpose of this study was to determine the angiogenic and wound healing effects of total alkaloid fraction from L. japonicus Houtt. (TALH) in vivo and in vitro. In addition, the main bioactive components of total alkaloids were to be identified and analyzed in this study. MATERIALS AND METHODS: First, the UHPLC/Q-TOF-MS method was used to identify and quantify the major components in the TALH extract. The wound healing activity was evaluated in vivo using a rat full-thickness cutaneous wound model. Histological study of wound healing in rat model was performed via immunohistochemistry and immunofluorescence. Cell proliferation was determined by MTT assay. Wound healing and transwell assays were used for detection of cell migration. The effect on tube formation was determined by tube formation assay in HUVECs. Western blot and RT-PCR were used to detect the expressions of relative proteins and genes respectively. Knock-down of SRC by siRNA was done to verify the crucial role of SRC in promotion of angiogenesis induced by TALH. RESULTS: Seven characteristic peaks were recognized in the UHPLC/Q-TOF-MS spectrum, while four of the main components were quantified. The wound model in rats showed that treatment of TALH promoted wound healing by stimulating cellular proliferation and collagen deposition. In vitro experiments showed that co-treatment of TALH and VEGF increased cell proliferation, migration and tube formation in HUVECs. Mechanistic studies suggested that the co-treatment increased gene expressions of SRC, MEK1/2 and ERK1/2, as well as the phosphorylation levels of these proteins. Furthermore, the effect of co-treatment was attenuated after SRC knockdown, suggesting that SRC plays an important role in angiogenesis and wound healing induced by TALH and VEGF co-treatment. CONCLUSION: Our results showed that TALH was one of the main active components of L. japonicus that promoted angiogenesis and wound healing by regulating the SRC/MEK/ERK pathway. Our study provided scientific basis for better clinical application of L. japonicas.