The dose-effect relationship of acupuncture on limb dysfunction after acute stroke: a systematic review and meta-analysis.

Objective: This study aimed to investigate the relationship between the dose and efficacy of acupuncture in treating limb dysfunction during acute stroke. Methods: Studies were searched from seven databases, including PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), VIP information database (VIP), and China Biology Medicine Database (CBM). All databases were searched until August 1, 2023 from inception. The risk of bias was assessed using Cochrane Collaboration's risk of bias tool (RoB2). Meta-analyses were performed using RevMan V.5.4 and Stata 12.0 statistical software. We used Fugl-Meyer Assessment (FMA) to measure recovery of limb dysfunction, NIH Stroke Scale (NIHSS) to measure neurological deficits, and Barthel index, Modified Barthel Index (MBI), and Activities of Daily Living (ADL) to measure activities of daily living. The primary outcome measure is FMA. After examining and integrating the raw data, we performed a meta-analysis using a 3-step process. First, we investigated the dose-related effects of acupuncture at varying doses and determined the optimal dosage for maximum therapeutic benefits. Second, we determined the difference between post-intervention and baseline scores on the outcomes of interest to determine minimal clinically important differences (MCID) to provide evidence for clinical treatment. Third, by combining the results of step 1 and step 2, we made the recommendations employing the Grades of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Results: Twenty-six studies containing 1947 participants were included, among which 61.5% of RCTs had a low risk of bias. Through the three-step analysis, the effect in improving limb dysfunction of acute stroke varied across different acupuncture dosages. Regarding the frequency of acupuncture, the results demonstrated a significant improvement in the low (every other day) and moderate-frequency (once a day) groups (low frequency: MD: 9.02, 95%CI: 5.40-12.64, p < 0.00001; moderate frequency: MD: 10.11, 95%CI: 5.05-15.18, p < 0.00001, heterogeneity (p = 0.87), I2 = 0%). For the acupuncture retention time, the results showed no significant difference between the short and medium retention groups (short retention time: MD: 0.05, 95% CI: -0.21-0.31, p = 0.71; medium retention time: MD: -1.16, 95% CI: -2.80-0.48, p = 0.17, heterogeneity (p < 0.00001), I2 = 99%). For the course of acupuncture, the results showed a significant improvement in the short course treatment (less than 2 weeks) group (MD: 14.87, 95% CI: 12.18-17.56, p < 0.00001, heterogeneity (p = 0.45), I2 = 0%). Conclusion: Our study demonstrated the effectiveness of different acupuncture dose in improving limb dysfunction. The pooled data suggested that the optimal intervention dose for acupuncture interval time was low (every other day) and moderate frequency (once a day), the optimal intervention dose for needle course time was short course treatment (less than 2 weeks). But we did not find the optimal intervention dose for needle retention time. Future studies of higher quality are needed to confirm this.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, CRD42023447202.

Supramolecular Assembly Based on Calix(4)arene and Aggregation-Induced Emission Photosensitizer for Phototherapy of Drug-Resistant Bacteria and Skin Flap Transplantation.

Photodynamic therapy as a burgeoning and non-invasive theranostic technique has drawn great attention in the field of antibacterial treatment but often encounters undesired phototoxicity of photosensitizers during systemic circulation. Herein, a supramolecular substitution strategy is proposed for phototherapy of drug-resistant bacteria and skin flap repair by using macrocyclic p-sulfonatocalix(4)arene (SC4A) as a host, and two cationic aggregation-induced emission luminogens (AIEgens), namely TPE-QAS and TPE-2QAS, bearing quaternary ammonium group(s) as guests. Through host-guest assembly, the obtained complex exhibits obvious blue fluorescence in the solution due to the restriction of free motion of AIEgens and drastically inhibits efficient type I ROS generation. Then, upon the addition of another guest 4,4'-benzidine dihydrochloride, TPE-QAS can be competitively replaced from the cavity of SC4A to restore its pristine ROS efficiency and photoactivity in aqueous solution. The dissociative TPE-QAS shows a high bacterial binding ability with an efficient treatment for methicillin-resistant Staphylococcus aureus (MRSA) in dark and light irradiation. Meanwhile, it also exhibits an improved survival rate for MRSA-infected skin flap transplantation and largely accelerates the healing process. Thus, such cascaded host-guest assembly is an ideal platform for phototheranostics research.

Network pharmacology and molecular docking-based study on exploring the potential mechanism of Lycium barbarum L: In the treatment of atherosclerosis.

BACKGROUND: Goji berries (Lycium barbarum L) are herbal medicine that have a long history of use and multiple pharmacological activities. In this study, we investigated the potential therapeutic effects of Goji berries on atherosclerosis (AS) using network pharmacology and molecular docking. METHODS: The active compounds of Goji berries were identified using the Traditional Chinese Medicine Systems Pharmacology platform, as well as the literature and the targets of each active compound were obtained using the Swiss Target Prediction database. The AS-related targets were collected from the GeneCards and OMIM databases to obtain the common targets of Goji berries and AS. The drug-compound-target-disease network and protein-protein interaction network were constructed using the Cytoscape software to obtain the core target proteins of Goji berries related to AS. Gene ontology analysis of the core targets and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed by Metascape. The target-chemical correlations were verified using AutoDock molecular docking. RESULTS: After analysis, 44 active compounds within Goji berries were obtained that exhibit associations with AS. Among these, the proteins exhibiting the highest degrees of interaction within the compound-targeted protein protein-protein interaction network were AKT1, SRC, MAPK3, MAPK1, RELA, and STAT3. The gene ontology-biology process analysis showed that compound-targeted proteins were mainly involved in regulating small molecule metabolic process, cellular response to chemical stress, reactive oxygen species metabolic process, and regulation of inflammatory response. Kyoto encyclopedia of genes and genomes pathway mainly included lipid and AS in which AKT1, SRC, MAPK3, and MAPK1 were involved. Advanced glycation end-product-receptor for advanced glycation end-product signaling pathway in diabetic complications, Chagas disease, and pancreatic disease. Molecular docking assessment showed that fucosterol is bound to AKT1, MAPK3, and SRC. CONCLUSION: This study demonstrates that network pharmacology and molecular docking analyses contribute to a better understanding of Goji berries active compounds and targets as potential therapeutic drugs for treating AS.

Boosting CO2 Electroreduction to C2H4 via Unconventional Hybridization: High-Order Ce4+ 4f and O 2p Interaction in Ce-Cu2O for Stabilizing Cu.

Efficient conversion of carbon dioxide (CO2) into value-added materials and feedstocks, powered by renewable electricity, presents a promising strategy to reduce greenhouse gas emissions and close the anthropogenic carbon loop. Recently, there has been intense interest in Cu2O-based catalysts for the CO2 reduction reaction (CO2RR), owing to their capabilities in enhancing C-C coupling. However, the electrochemical instability of Cu+ in Cu2O leads to its inevitable reduction to Cu0, resulting in poor selectivity for C2+ products. Herein, we propose an unconventional and feasible strategy for stabilizing Cu+ through the construction of a Ce4+ 4f-O 2p-Cu+ 3d network structure in Ce-Cu2O. Experimental results and theoretical calculations confirm that the unconventional orbital hybridization near Ef based on the high-order Ce4+ 4f and 2p can more effectively inhibit the leaching of lattice oxygen, thereby stabilizing Cu+ in Ce-Cu2O, compared with traditional d-p hybridization. Compared to pure Cu2O, the Ce-Cu2O catalyst increased the ratio of C2H4/CO by 1.69-fold during the CO2RR at -1.3 V. Furthermore, in situ and ex situ spectroscopic techniques were utilized to track the oxidation valency of copper under CO2RR conditions with time resolution, identifying the well-maintained Cu+ species in the Ce-Cu2O catalyst. This work not only presents an avenue to CO2RR catalyst design involving the high-order 4f and 2p orbital hybridization but also provides deep insights into the metal-oxidation-state-dependent selectivity of catalysts.

[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.

Pollutant impacts on bacteria in surface water and sediment: Conventional versus emerging pollutants in Taihu Lake, China.

Bacteria play a critical role in biogeochemical cycling, self-purification, and food web fueling in surface freshwater ecosystems. However, the comparison between the impacts of conventional and emerging pollutants on the bacteria in surface water and sediment remains unclear and requires for an in-depth understanding to assess ecological risk and select associated bioindicators. Taihu Lake, a typical shallow lake in China, was divided into pollutant impacted and less-impacted zones for sampling. Spatial distributions of conventional pollutants, emerging pharmaceuticals, and bacterial communities were investigated in surface water and sediment. The correlations of pollutants with bacterial communities and the variations in bacterial functions were analyzed to help assess the pollutant influences on bacteria. The results showed that the water quality index and trophic level index across the whole lake were at medium to good, and mesotropher to light eutropher grades, respectively, indicating a relatively good control on conventional pollutants in water. Target pharmaceuticals were at much higher concentrations in water of the impacted zone compared to the less-impacted zone, exhibiting close positive relationships with the bacterial phyla in the impacted water. The ratio of Firmicutes to Proteobacteria in surface water is suggested as a plausible bioindicator to evaluate the level of inflow pharmaceutical contamination and the risk of relevant bacterial resistance in the outflow. In sediment, no significant difference was observed for pharmaceuticals between the two zones, whereas total phosphorus and orthophosphate were substantially higher in the impacted zone. Phosphorus pollutants were tightly associated with the bacterial genera in the impacted sediment, likely relating to the increase in iron- or sulfate-reducing bacteria which implies the potential risk of phosphorus releasing from sediment to water.

Formosanin C inhibits non-small-cell lung cancer progression by blocking MCT4/CD147-mediated lactate export.

BACKGROUND: Tumor cells reprogram their metabolic network to maintain their uncontrolled proliferation, metastasis, and resistance to cancer therapy. Treatments targeting abnormal cellular metabolism may have promising therapeutic effects. Formosanin C (FC), a diosgenin derived from the rhizoma of Paris polyphylla var. yunnanensis, has shown potent anti-cancer activities against various cancer types. However, the effect of FC on cancer metabolism remains to be elucidated. PURPOSE: In this research, we aimed to elucidate FC's effect and potential mechanisms on metabolism in lung cancer. METHODS: Colony formation, transwell cell migration, and apoptosis were detected in multiple NSCLC cell lines to assess the cytotoxicity of FC. 1H NMR metabolomics approach was applied to screen the differential metabolites in H1299 cells and the culture medium. Western blotting, flow cytometry, and other molecular biological techniques were performed to verify the latent mechanism involved in metabolites. An allograft tumor model was employed to investigate the anti-tumor effects of FC in vivo. RESULTS: FC significantly inhibited monoclonal formation and migration and induced cell cycle arrest and apoptosis in NSCLC cells. FC altered the abundances of 12 metabolites in lung cancer cells and 3 metabolites in the medium. These differential metabolites are primarily involved in glycolysis, citric acid cycle, and glutathione pathways. Notably, there was a remarkable increase in intracellular lactate and a reduction in extracellular lactate after FC treatment. Mechanically, FC downregulated the expression of MCT4 and CD147, blocking the export of lactate. Furthermore, FC also evoked mitochondrial dysfunction coupled with excessive oxidative stress, decreased mitochondrial membrane potential, ATP production reduction, glutathione depletion, and Ca2+ overload. Moreover, FC suppressed tumor progression in vivo with reduced protein levels of the MCT4 and CD147 in tumor tissues. CONCLUSION: FC inhibits lung cancer growth by the novel mechanism in which MCT4/CD147-mediated inhibition of lactate transport and disruption of mitochondrial functions are involved.

Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors.

Alterations in histone modification have been linked to cancer development and progression. Celastrol, a Chinese herbal compound, shows potent anti-tumor effects through multiple signaling pathways. However, the involvement of histone modifications in this process has not yet been illustrated. In this study, barcode sequencing of a eukaryotic genome-wide deletion library revealed that histone modifications, especially histone acetylation associated with the NuA4 histone acetyltransferase complex, were involved in the anti-proliferation actions of celastrol. The essential roles of histone modification were verified by celastrol sensitivity tests in cells lacking specific genes, such as genes encoding the subunits of the NuA4 and Swr1 complex. The combination of celastrol and histone deacetylase inhibitors (HDACi), rather than the combination of celastrol and histone acetyltransferase inhibitors, synergistically suppressed cancer cell proliferation. In addition to upregulating H4K16 acetylation (H4K16ac), celastrol regulates H3K4 tri-methylation and H3S10 phosphorylation. Celastrol treatment significantly enhanced the suppressive effects of HDACi on lung cancer cell allografts in mice, with significant H4K16ac upregulation, indicating that a combination of celastrol and HDACi is a potential novel therapeutic approach for patients with lung cancer.

Intracavitary physiotherapy combined with acupuncture mediated AMPK/mTOR signalling to improve endometrial receptivity in patients with thin endometrium.

OBJECTIVE: To explore the mechanism of intracavitary physiotherapy combined with acupuncture to improve the receptivity of thin endometrium. METHODS: From October 2020 to April 2021, 40 patients diagnosed with thin endometrium and preparing for hormone replacement cycle freeze-thaw embryo transfer in our centre for Reproduction were included, 40 patients were randomized to treatment group and control group. 20 patients with normal endometrium during the same period were selected as the normal group.All patients underwent freeze-thaw embryo transfer using hormone replacement cycles.The treatment group added endovascular physiotherapy combined with acupuncture. RESULTS: The endometrial receptivity of the patients with thin endometrium was significantly lower than that of the normal group(P < 0.01). Endovascular therapy combined with acupuncture can significantly increase endometrial thickness in patients with thin endometrium and the proportion of patients with type A endometrium, reduce bilateral Uterine arterial pulsatilityindex (PI), Uterine arterial resistance index (RI), and peaksystolicvelocity/diastolicvelocity (S/D), upregulate the expression of HOXA10 protein and mRNA in endometrium tissue, and improve the rate of embryo implantation and clinical pregnancy(P < 0.01).there was no significant difference between the treatment group and the normal group (P > 0.05). This may be related to the regulation of the AMPK/mTOR signalling pathway by intracavitary physiotherapy combined with acupuncture, downregulation of the expression of the AMPK gene and protein and upregulation of the expression of the mTOR gene and protein. CONCLUSIONS: 1. Abnormal energy metabolism is present in the endometrium of patients with thin endometrium, which affects the autophagy process and leads to a decrease in the receptivity of thin endometrium. 2. Intracavitary physiotherapy combined with acupuncture mediated the AMPK/mTOR pathway to improve energy metabolism, promote the autophagy process, improve endometrial morphology and ultrasonic indicators of patients, upregulate the expression of endometrial receptivity-related HOXA10 genes and proteins, and improve the embryo implantation rate and clinical pregnancy rate.

Complanatoside A targeting NOX4 blocks renal fibrosis in diabetic mice by suppressing NLRP3 inflammasome activation and autophagy.

BACKGROUND: Diabetic nephropathy (DN) is an important cause of end-stage renal disease. Complanatoside A (CA), an active component from Semen Astragali Complanati, has been reported to be a potential candidate for the treatment of kidney diseases. However, the underlying mechanisms and protective effects of CA in DN remain unclear. PURPOSE: In this paper, the effects and the mechanism of CA against ameliorating DN were investigated in vivo and in vitro. STUDY DESIGN: Here, a high-fat diet/streptozotocin-induced diabetic model and TGF-ß1-induced HK-2 cells were used to explore the protective effects and mechanisms of CA on DN in vivo and in vitro. METHODS: Major biochemical indexes, Histopathological morphology, and Immunohistochemistry have explored the therapeutic effect of CA on DN. Subsequently, TGF-ß1-induced HK-2 cells were utilized to investigate the anti-renal fibrosis effect of CA. Finally, the mechanism of CA against renal fibrosis was studied via western blotting, immunofluorescence, transfection, and molecular docking. RESULTS: The results showed that CA attenuated glomerular hypertrophy, collagen matrix deposition, and tubular interstitial fibrosis in diabetic mice. Moreover, the activation of TGF-ß1-inducible epithelial-mesenchymal transition (EMT) was hindered by CA treatment in HK-2 cells. Mechanistically, the data suggested that upregulated NOX4 during diabetes and TGF-ß1 in HK-2 cells was prominently diminished after CA treatment. Furthermore, CA exposure inhibited NLRP3 inflammasome activation and downstream inflammation gene expression such as IL-18 and IL-1ß in vivo and vitro. These findings indicated that CA obstructed the EMT to protect renal tubular epithelial cells against fibrosis via blocking NLRP3 activation, which was associated with inhibiting NOX4. Besides, the markedly raised autophagy levels in the diabetic model characterized by increasing LC3II/LC3I and Beclin1 were reversed after CA treatment, which is also a pivotal mechanism against renal fibrosis. More importantly, specific NOX4 overexpressed in HK-2 cells abolished that CA exposure blocked TGF-ß1-induced-EMT, ROS generation, NLRP3, and autophagy activation. Meanwhile, the inhibition of cell migration, ROS generation, autophagy, and renal inflammation after CA treatment was more pronounced in NOX4-deficient HK-2 cells. CONCLUSION: Our findings provided evidence that CA might be a potential therapeutic agent for DN by ameliorating NLRP3 inflammasome and autophagy activation via targeting NOX4 inhibition.

Efficacy and Safety of Intravitreal Injection of Triamcinolone Acetonide and Conbercept for Intraocular Lens after Cataract Surgery.

Objective: To investigate the effect of intravitreal injection of triamcinolone acetonide and conbercept on the efficacy and safety of diabetic macular edema (DME) after cataract intraocular lens (IOL) surgery. Methods: A total of 350 patients with cataract complicated with diabetic macular edema in our hospital from January 2017 to July 2021 were randomly divided into conbercept group and triamcinolone acetonide group. Patients in the conbercept group were given intravitreal injection of conbercept during IOL surgery, and patients in the triamcinolone acetonide group were given injection of triamcinolone acetonide during surgery. Results: Three months after treatment, the best-corrected visual acuity of the two groups was significantly higher than before, the corrected visual acuity of the conbercept group was more significant than the triamcinolone acetonide group, and the intraocular pressure of the triamcinolone acetonide group was higher than the conbercept group. The foveal thickness and macular volume were significantly reduced in both groups, and was reduced more in the conbercept group than in the triamcinolone acetonide group. The contents of VEGF, SDF-1, and IL-6 in both groups were significantly decreased, and the decrease was more significant in the conbercept group than in the triamcinolone acetonide group. The patients with elevated intraocular pressure, headache and vomiting, orbital swelling pain, eye swelling pain, and eye pain in the triamcinolone acetonide group were significantly higher than those in the conbercept group (P < 0.05). Conclusions: Conbercept and triamcinolone acetonide has a good therapeutic effect on DME in pseudophakic eyes after cataract IOL surgery, which can reduce the degree of macular edema and improve the visual function. However, the therapeutic effect of injection therapy with conbercept is safe, the prognosis is better, and the complication rate is low.

Ferroptosis and its emerging role in tumor.

Ferroptosis is a novel form of programmed cell death characterized by iron-dependent lipid peroxidation accumulation. It is morphologically, biochemically, and genetically distinct from other known cell death, such as apoptosis, necrosis, and pyroptosis. Its regulatory mechanisms include iron metabolism, fatty acid metabolism, mitochondrial respiration, and antioxidative systems eliminating lipid peroxidation, such as glutathione synthesis, selenium-dependent glutathione peroxidase 4, and ubiquinone. The disruption of cellular redox systems causes damage to the cellular membrane leading to ferroptotic cell death. Recent studies have shown that numerous pathological diseases, like tumors, neurodegenerative disorders, and ischemia-reperfusion injury are associated with ferroptosis. As such, pharmacological regulation of ferroptosis either by activation or by suppression will provide a vast potential for treatments of relevant diseases. This review will discuss the advanced progress in ferroptosis and its regulatory mechanisms from both the antioxidative and oxidative sides. In addition, the roles of ferroptosis in various tumorigenesis, development, and therapeutic strategies will be addressed, particularly to chemotherapy and immunotherapy, as well as the discoveries from Traditional Chinese Medicine. This review will lead us to have a comprehensive understanding of the future exploration of ferroptosis and cancer therapy.

Irisin deficiency disturbs bone metabolism.

Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone-like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx-Cre:FNDC5/irisin KO mice, in which FNDC5/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early-stage to adulthood. Our phenotypical analysis exhibited decreased osteoblast-related gene expression and increased osteoclast-related gene expression in bone tissues, and reduced adipose tissue browning due to bone-born irisin deletion. By harvesting and culturing MSCs from the knockout mice, we found that osteoblastogenesis was inhibited and osteoclastogenesis was increased. By using irisin stimulated wildtype primary cells as a gain-of-function model, we further revealed the effects and mechanisms of irisin on promoting osteogenesis and inhibiting osteoclastogenesis in vitro. In addition, positive effects of exercise, including bone strength enhancement and body weight loss were remarkably weakened due to irisin deficiency. Interestingly, these changes can be rescued by supplemental administration of recombinant irisin during exercise. Our study indicates that irisin plays an important role in bone metabolism and the crosstalk between bone and adipose tissue. Irisin represents a potential molecule for the prevention and treatment of bone metabolic diseases.

Exploration of resistance to Phelipanche aegyptiaca in tomato.

BACKGROUND: Cultivated tomatoes are highly susceptible to the destructive parasite Phelipanche aegyptiaca. Wild relatives show the potential resistance for genetic improvement. However, their genetic and molecular mechanisms are still unknown. RESULTS: Among 50 wild tomato accessions were evaluated for resistance to P. aegyptiaca, most of the wild relatives exhibited varying degrees of resistance compared to the cultivars. Solanum pennellii LA0716 performed the most promising and solid resistance with very low infection by the broomrape. The resistance involved in LA0716 was further confirmed by cytological analysis, and explored by employing a permanent introgression line (IL) population. Thirteen putative quantitative trait loci (QTLs) conferring the different resistance traits were identified. They are located on chromosomes 1, 2, 3, 4, 6, 8 and 9. The most attractive QTLs are positioned in IL6-2 and overlap with IL6-3. Specially, IL6-2 showed the highest and most consistent resistance for multiple traits and explained the major phenotypic variation of LA0716. Analysis of candidate genes involved in these regions showed that Beta (Solyc06g074240) and P450 (Solyc06g073570, Solyc06g074180 and Solyc06g074420) genes are substantially related to the strigolactone (SL) pathway. Transcript analysis further demonstrated that both Solyc06g073570 and Solyc06g074180 might play an important role in the reduction of P. aegyptiaca infection. CONCLUSION: Germplasms resistant to P. aegyptiaca were found in wild tomato species. QTLs conferring P. aegyptiaca tolerance in LA0716 were identified. IL6-2 is identified as a prospective line possessing the major QTLs. The candidate genes would provide the availability to assist the introgression of the resistance in future breeding programmes. © 2020 Society of Chemical Industry.

A systematic comparative study on morphological, crystallinity, pasting, thermal and functional characteristics of starches resources utilized in China.

In this study, starches from diverse botanical sources (arrowroot, cassava, Chinese yam, fern root, kidney beans, lotus seed, taro, and water chestnut) were isolated and examined for morphological, pasting, thermal, and physico-chemical characteristics in order to distinguish their end use potential. Among isolated starches significant differences (p < 0.05) were observed in gelatinization temperatures, morphology, color, pasting, and functional properties. Amylose content of isolated starches varied between 17.12% and 35.62%. X-ray diffraction pattern of isolated starches displayed A-type (arrowroot, cassava, corn, and kidney bean), B-type (potato) and C-type (water chestnut, taro, Chinese yam, fern root, and lotus seed) crystalline pattern. The FT-IR spectra of isolated starches confirmed their carbohydrate nature. Furthermore, the current study affords information for the exploitation of isolated starches from the diverse botanical sources cultivated in China that would be convenient for commercial applications.

Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have demonstrated clinical benefits in the treatment of several tumour types. However, the emergence of TKI resistance restricts the therapeutic effect. This study uses non-small cell lung cancer (NSCLC) to explore the mechanisms contributing to TKI resistance in tumours. METHODS: Biological phenotypes and RNA microarray expression data were analysed in NSCLC cells with and without TKI pretreatment. Specific inhibitors and siRNAs were used to validate the direct involvement of an AKT/FOXM1/STMN1 pathway in TKI resistance. Patients' tissues were analysed to explore the clinical importance of FOXM1 and STMN1. RESULTS: In vitro and in vivo studies showed that TKIs induced the enrichment of cancer stem cells (CSC), promoted epithelial to mesenchymal transition (EMT), and conferred multidrug resistance on NSCLC cells in a cell type- and TKI class-dependent manner. Mechanistically, TKIs activated an AKT/FOXM1/STMN1 pathway. The crucial role of this pathway in TKI-induced enrichment of CSC and drug resistance was verified by silencing FOXM1 and STMN1 or blocking the AKT pathway. Additionally, overexpression of STMN1 was associated with upregulation of FOXM1 in advanced NSCLC patients, and STMN1/FOXM1 upregulation predicted a poor outcome. CONCLUSIONS: Our findings elucidate an additional common mechanism for TKI resistance and provide a promising therapeutic target for reversing TKI resistance in NSCLC.

Green tea epigallocatechin-3-gallate alleviates Porphyromonas gingivalis-induced periodontitis in mice.

Porphyromonas gingivalis causes inflammation, and leads to the periodontitis in gingival tissue damage and bone resorption. Epigallocatechin-3-gallate (EGCG) is a major polyphenol extract from green tea with plenty of pharmacological functions. The aim of this study was to determine whether continuous oral intake of EGCG would alleviate P. gingivalis-induced periodontitis. Eight-week BALB/c mice were administered with EGCG (0.02%) or vehicle in drinking water. They were fed normal food and orally infected with P. gingivalis every 2days, up to a total of 20 times, and then sacrificed at 15weeks of age. The P. gingivalis-challenged group markedly increased alveolar bone resorption of the maxillae in BALB/c mice by Micro-CT detection, and administration of EGCG resulted in a significant reduction in bone loss. Inflammation cytokine antibody array and enzyme linked immunosorbent assay revealed that some inflammatory mediators in serum were increased by P. gingivalis infection, but were lowered after EGCG treatment. High positive areas of IL-17 and IL-1ß in the gingival tissue were observed in the P. gingivalis-challenged mice, and were reduced by EGCG treatment. Real-time polymerase chain reaction (PCR) analyses also showed the expressions of IL-1ß, IL-6, IL-17, IL-23, TNF-α and other mediators in gingival tissue were higher in P. gingivalis-challenged mice, and were down-regulated with EGCG treatment, except IL-23. Our results suggest that EGCG, as a natural healthy substance, probably alleviates P. gingivalis-induced periodontitis by anti-inflammatory effect.

Detection of an inversion in the Ty-2 region between S. lycopersicum and S. habrochaites by a combination of de novo genome assembly and BAC cloning.

KEY MESSAGE: A chromosomal inversion associated with the tomato Ty - 2 gene for TYLCV resistance is the cause of severe suppression of recombination in a tomato Ty - 2 introgression line. Among tomato and its wild relatives inversions are often observed, which result in suppression of recombination. Such inversions hamper the transfer of important traits from a related species to the crop by introgression breeding. Suppression of recombination was reported for the TYLCV resistance gene, Ty-2, which has been introgressed in cultivated tomato (Solanum lycopersicum) from the wild relative S. habrochaites accession B6013. Ty-2 was mapped to a 300-kb region on the long arm of chromosome 11. The suppression of recombination in the Ty-2 region could be caused by chromosomal rearrangements in S. habrochaites compared with S. lycopersicum. With the aim of visualizing the genome structure of the Ty-2 region, we compared the draft de novo assembly of S. habrochaites accession LYC4 with the sequence of cultivated tomato ('Heinz'). Furthermore, using populations derived from intraspecific crosses of S. habrochaites accessions, the order of markers in the Ty-2 region was studied. Results showed the presence of an inversion of approximately 200 kb in the Ty-2 region when comparing S. lycopersicum and S. habrochaites. By sequencing a BAC clone from the Ty-2 introgression line, one inversion breakpoint was identified. Finally, the obtained results are discussed with respect to introgression breeding and the importance of a priori de novo sequencing of the species involved.

The Ph-3 gene from Solanum pimpinellifolium encodes CC-NBS-LRR protein conferring resistance to Phytophthora infestans.

KEY MESSAGE: Ph-3 is the first cloned tomato gene for resistance to late blight and encodes a CC-NBS-LRR protein. Late blight, caused by Phytophthora infestans, is one of the most destructive diseases in tomato. The resistance (R) gene Ph-3, derived from Solanum pimpinellifolium L3708, provides resistance to multiple P. infestans isolates and has been widely used in tomato breeding programmes. In our previous study, Ph-3 was mapped into a region harbouring R gene analogues (RGA) at the distal part of long arm of chromosome 9. To further narrow down the Ph-3 interval, more recombinants were identified using the flanking markers G2-4 and M8-2, which defined the Ph-3 gene to a 26 kb region according to the Heinz1706 reference genome. To clone the Ph-3 gene, a bacterial artificial chromosome (BAC) library was constructed using L3708 and one BAC clone B25E21 containing the Ph-3 region was identified. The sequence of the BAC clone B25E21 showed that only one RGA was present in the target region. A subsequent complementation analysis demonstrated that this RGA, encoding a CC-NBS-LRR protein, was able to complement the susceptible phenotype in cultivar Moneymaker. Thus this RGA was considered the Ph-3 gene. The predicted Ph-3 protein shares high amino acid identity with the chromosome-9-derived potato resistance proteins against P. infestans (Rpi proteins).