Graphene enhances artemisinin production in the traditional medicinal plant Artemisia annua via dynamic physiological processes and miRNA regulation.

We investigated the effects of graphene on the model herb Artemisia annua, which is renowned for producing artemisinin, a widely used pharmacological compound. Seedling growth and biomass were promoted when A. annua was cultivated with low concentrations of graphene, an effect which was attributed to a 1.4-fold increase in nitrogen uptake, a 15%-22% increase in chlorophyll fluorescence, and greater abundance of carbon cycling-related bacteria. Exposure to 10 or 20 mg/L graphene resulted in a âˆ¼60% increase in H2O2, and graphene could act as a catalyst accelerator, leading to a 9-fold increase in catalase (CAT) activity in vitro and thereby maintaining reactive oxygen species (ROS) homeostasis. Importantly, graphene exposure led to an 80% increase in the density of glandular secreting trichomes (GSTs), in which artemisinin is biosynthesized and stored. This contributed to a 5% increase in artemisinin content in mature leaves. Interestingly, expression of miR828 was reduced by both graphene and H2O2 treatments, resulting in induction of its target gene AaMYB17, a positive regulator of GST initiation. Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA (miRNA) biogenesis through Dicers and regulates the miR828-AaMYB17 module, thus affecting GST density. Our results suggest that graphene may contribute to yield improvement in A. annua via dynamic physiological processes together with miRNA regulation, and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.

A novel perspective on the preventive treatment of hydrazine compound-induced liver injury: Isoniazid liver injury as an example.

ETHNOPHARMACOLOGICAL RELEVANCE: Anethum graveolens L. (dill), which has been used as a medicine, spice and aromatic plant since ancient times, is not only a traditional Chinese medicines but also an important medicinal and functional food in Europe and Central and South Asia. In ethnomedicine, dill reportedly exerts a protective effect on the liver and has been widely used as a traditional medicine for the treatment of jaundice in the liver and spleen and inflammatory gout diseases in Saudi Arabia. Furthermore, studies have found that dill can regulate the NAT2 enzyme, and this plant was thus selected to study its alleviating effect on isoniazid liver injury. AIM OF THE STUDY: The purpose of this study was to explore the effect of dill on alleviating liver injury induced by hydrazine compounds represented by isoniazid through the use of network pharmacology combined with in vivo and in vitro experimental verifications. MATERIALS AND METHODS: First, we screened the key targets of dill in the treatment of liver injury through the use of network pharmacology; we then performed GO and KEGG pathway enrichment analyses using the DAVID database. We also verified the alleviative and anti-inflammatory effects of dill on isoniazid liver injury in rats by animal experiments. We further investigated the modulating effect of dill on the enzymatic activity of NAT2, a common metabolizing enzyme of hydrazine compounds. RESULTS: A total of 111 key targets were screened through network pharmacology. In vivo experiments showed that dill reduced the amount of inflammatory factors produced by isoniazid, such as IL-10, IL-1ß, TNF-α and IL-6, restored the levels of ALT, AST, r-GT, AKP and TBA in vivo, and attenuated isoniazid liver injury. Both in vivo and vitro results indicated that dill could regulate the expression of NAT2 enzymes. CONCLUSIONS: The results tentatively demonstrate that dill can alleviate isoniazid liver injury through multiple components, targets and pathways and exerts a regulatory effect on the NAT2 enzyme, and these findings thus provide new ideas for subsequent studies on hydrazide liver injury--reducing the risk of hydrazide-induced liver injury through anti-inflammation and regulation of NAT2 enzymes.

Acupuncture for dyspnea and breathing physiology in chronic respiratory diseases: A protocol of a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dyspnea is one of the most common symptoms of chronic respiratory disease (CRD) and is closely related to increased functional disability and mortality, resulting in substantial adverse outcomes on patients and imposing great social and economic burden. Although multiple clinical trials and systematic reviews have suggested that acupuncture could be effective in treating COPD and lung cancer, little is known about its effects on dyspnea relief in patients with CRD. The present study aimed to use a systematic review approach to evaluate the effectiveness and safety of acupuncture in the treatment of dyspnea in patients with CRD. METHODS: We will search the following 9 databases from inception to June 30, 2022, PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, WANFANG Database, Chinses Scientific and Technological Periodical Database, and Chinese Biomedical Database, and the Cochrane Library Database. Clinical randomized controlled trials in English or Chinese that evaluate invasive acupuncture versus control group in treatment of CRD with dyspnea will be included. The primary outcome will be dyspnea scores, breathing physiological function, and the secondary outcomes include exercise tolerance by six-minute walk distance quality of life, quality of life and adverse events. Two reviewers will independently conduct study selection, data extraction and quality assessment. The Review Manager software will be used for meta-analysis. This protocol will be carried out in accordance with the PRISMA-P guidance. CONCLUSION: This systematic review and meta-analysis will provide the evidence of whether acupuncture is an effective and safe intervention for CRD with dyspnea. The results will be disseminated through peer-reviewed publication.

Community Dynamics in Structure and Function of Honey Bee Gut Bacteria in Response to Winter Dietary Shift.

Temperate honey bees (Apis mellifera) are challenged by low temperatures and abrupt dietary shifts associated with behavioral changes during winter. Case studies have revealed drastic turnover in the gut microbiota of winter bees, highlighted by the seasonal dominance of a non-core bacterium Bartonella. However, neither biological consequence nor underlying mechanism of this microbial turnover is clear. In particular, we ask whether such changes in gut profile are related to winter dietary shift and possibly beneficial to host and associated gut microbiome? Here, we integrated evidences from genomics, metagenomics, and metabolomics in three honey bee subspecies maintained at the same locality of northern China to profile both diversity and functional variations in gut bacteria across seasons. Our results showed that winter dominance of Bartonella was shared in all tested honey bee lineages. This seasonal change was likely a consequence of winter dietary shifts characterized by greatly reduced pollen consumption and accumulation of metabolic waste due to restricted excretion. Bartonella showed expanded genomic capacity in utilizing more diverse energy substrates, such as converting metabolic wastes lactate and ethanol into pyruvate, an energy source for self-utilization and possibly also for host and other symbionts. Furthermore, Bartonella was the only bacterium capable of both producing and secreting tryptophan and phenylalanine, whose metabolic products were detected in bee guts, even though all gut bacteria lacked relevant digestion enzymes. These results thus suggested a possible mechanism where the gut bacteria might benefit the host by supplementing them with essential amino acids lacking in a protein shortage diet. IMPORTANCE The abilities to survive winter and to adapt to major food changes are key traits that have enabled successful range expansion of the honey bees from the tropic to temperate climate. Our results highlighted a new possibility that gut bacteria may have played an important role in host survival of the severe winter condition. The non-core bacterium Bartonella is not only more adaptive to the winter diet but is also equipped with the capacity to provide the host with essential nutrients and important metabolic substrates. This overall host-bacterium profile is probably favored by natural selection, resulting in a consistent winter gut strategy across varied honey bee lineages. Conversely, when the hosts start to forage again, core bacteria maintained at low abundance during winter returned to their typical dominant status, thus completing the annual gut turnover. Our study suggests a new hypothesis where seasonal gut variations may improve the fitness of the honey bee, allowing them to explore more diverse climates.

A 2-oxoglutarate-dependent dioxygenase converts dihydrofuran to furan in Salvia diterpenoids.

Tanshinone ⅡA (TⅡA), a diterpene quinone with a furan ring, is a bioactive compound found in the medicinal herb redroot sage (Salvia miltiorrhiza Bunge), in which both furan and dihydrofuran analogs are present in abundance. Progress has been made recently in elucidating the tanshinone biosynthetic pathway, including heterocyclization of the dihydrofuran D-ring by cytochrome P450s; however, dehydrogenation of dihydrofuran to furan, a key step of furan ring formation, remains uncharacterized. Here, by differential transcriptome mining, we identified six 2-oxoglutarate-dependent dioxygenase (2-ODD) genes whose expressions corresponded to tanshinone biosynthesis. We showed that Sm2-ODD14 acts as a dehydrogenase catalyzing the furan ring aromatization. In vitro Sm2-ODD14 converted cryptotanshinone to TⅡA and thus was designated TⅡA synthase (SmTⅡAS). Furthermore, SmTⅡAS showed a strict substrate specificity, and repression of SmTⅡAS expression in hairy root by RNAi led to increased accumulation of total dihydrofuran-tanshinones and decreased production of furan-tanshinones. We conclude that SmTⅡAS controls the metabolite flux from dihydrofuran- to furan-tanshinones, which influences medicinal properties of S. miltiorrhiza.

Engineering high coenzyme Q10 tomato.

Coenzyme Q (CoQ) is vital for energy metabolism in living organisms. In humans, CoQ10 deficiency causes diseases and must be replenished via diet; however, CoQ content in plant foods is primarily low. Here, we report the breeding of high CoQ10 tomato lines by expressing four enzymes with a fruit-specific promoter, which modifies the chloroplast chorismate pathway, enhances cytosolic isoprenoid biosynthesis, and up-regulates the first two reactions in mitochondrion that construct the CoQ10 polyisoprenoid tail. We show that, while the level of the aromatic precursor could be markedly elevated, head group prenylation is the key to increasing the final CoQ10 yield. In the HUCD lines expressing all four transgenes, the highest CoQ10 content (0.15 mg/g dry weight) shows a seven-fold increase from the wild-type level and reaches an extraordinarily rich CoQ10 food grade. Overviewing the changes in other terpenoids by transcriptome and metabolic analyses reveals variable contents of carotenoids and α-tocopherol in the HUCD lines. In addition to the enigmatic relations among different terpenoid pathways, high CoQ10 plants maintaining substantial levels of either vitamin can be selected. Our investigation paves the way for the development of CoQ10-enriched crops as dietary supplements.

Clinical efficacy and safety of Chinese herbal medicine versus placebo for the treatment of chronic obstructive pulmonary disease: A systematic review and meta-analysis.

OBJECTIVE: Randomized clinical trials and published meta-analyses assessing the clinical effectiveness of Chinese herbal medicine (CHM) on the treatment of stable chronic obstructive pulmonary disease (COPD) yielded inconsistent results in terms of disease outcomes, in which the design of placebo-controlled studies can contribute to the heterogeneity. This study aimed to evaluate the efficacy and safety of CHM compared to placebo on the treatment of stable COPD, to provide robust evidence for the use of CHM in COPD. METHODS: Nine electronic databases were searched from inception to October 1, 2019 to identify placebo controlled randomized trials of CHM for the treatment of stable COPD and studies in English or Chinese were included. The primary outcomes were symptom score (CAT score), quality of life (SGRQ) and frequency of acute exacerbations. The secondary outcomes included lung function, clinical total effective rate and adverse events. The selection of studies, data extraction and coding and assessment of risk of bias of the included studies were conducted by two reviewers independently. Mean difference (MD) was used to analyze continuous variable and relative risk ratio (RR) for dichotomous data. RESULTS: A total of eleven studies involving 1223 patients were included. While maintaining routine western pharmacotherapies (WP), CHM had significant advantage over the treatment of placebo in improving CAT score (MD -3.93; 95 %CI -6.01 to -1.85) and SGRQ score (MD -6.20; 95 %CI -10.13 to -2.28), reducing the frequency of acute exacerbations (MD -0.78; 95 %CI -1.40 to -0.16) and improving clinical effective rate (RR 1.29; 95 %CI 1.14 to 1.45), but had no significant effect on improving FEV1%pred (MD 8.18; 95 %CI -4.22 to 20.58). High heterogeneity was found for the changes in exacerbation frequency and FEV1%pred. No serious adverse events related to CHM were reported. CONCLUSIONS: This meta-analysis of placebo-controlled RCTs demonstrated that the use of CHM in addition to WP could alleviate clinical symptoms, improve quality of life and clinical efficiency and reduce the frequency of exacerbations, which could be an alternative approach for treatment adjustment of COPD. CHM was a relatively safe treatment. These findings need to be verified in future with high-quality clinical trials.

Water-soluble ZnCuInSe quantum dots for bacterial classification, detection, and imaging.

Bacteria are everywhere and pose severe threats to human health and safety. The rapid classification and sensitive detection of bacteria are vital steps of bacterial community research and the treatment of infection. Herein, we developed optical property-superior and heavy metal-free ZnCuInSe quantum dots (QDs) for achieving rapid discrimination of Gram-positive/Gram-negative bacteria by the naked eye; driven by the structural differences of bacteria, ZnCuInSe QDs are effective in binding to Gram-positive bacteria, especially Staphylococcus aureus (S. aureus), in comparison with Gram-negative bacteria and give discernable color viewed by the naked eye. Meanwhile, based on its distinctive fluorescence response, the accurate quantification of S. aureus was investigated with a photoluminescence system in the concentration ranges of 1 × 103 to 1 × 1011 CFU/mL, with a limit of detection of 1 × 103 CFU/mL. Furthermore, we demonstrated the feasibility of ZnCuInSe QDs as a fluorescence probe for imaging S. aureus. This simple strategy based on ZnCuInSe QDs provides an unprecedented step for rapid and effective bacterial discrimination, detection, and imaging.

Melatonin ameliorates spatial memory and motor deficits via preserving the integrity of cortical and hippocampal dendritic spine morphology in mice with neurotrauma.

We aimed to elucidate the role of cortical and hippocampal dendritic spines on neurological deficits associated with hippocampal microgliosis, hippocampal neurogenesis, and neuroinflammation in mice with cortical compact impact (CCI) injury. In the present study, we found that CCI reduced spatial memory mean latency (10 s. vs 50 s) and motor dysfunction (130 s. vs 150 s.) in mice, as determined by Morris water maze and rotarod test, respectively. Golgi staining of cortical pyramidal neurons revealed that, compared to the controls, the CCI group treated with vehicle solution had significantly lower values of dendritic order (or dendritic branch number) (4.0 vs 6.2), total spine length (400 µm vs 620 µm) and spine density (40 spines/µm vs 60 spines/µm), but had significantly higher values of dendritic beading (40 beadings/mm vs 20 beadings/mm). Additionally, Sholl analysis showed that, compared to controls, the CCI + NS group mice had significantly lower values of dendritic intersections (1.0 vs 2.0). Immunofluorescence assay also revealed that, compared to controls, the CCI + NS group mice had significantly higher values of the newly formed hippocampal cells (1250/mm2 vs 1000/mm2) but significantly lower values of dendritic order (2.0 branch # vs 4.2 branch #), total spine length (180 µm vs 320 µm) and intersection (1.0 vs 3.0). The CCI + NS group mice further showed significantly higher numbers of microglia in the dentate gyrus of the hippocampus and higher concentrations of pro-inflammatory cytokines in the cerebrospinal fluids. All the CCI-induced spatial memory (40 s) and motor (150 s) dysfunction, deranged dendritic and spine morphology of cortical pyramidal neurons or hippocampal newly formed cells, hippocampal microgliosis, and central neuroinflammation were all significantly reduced by melatonin administration during post-CCI. Simultaneously, melatonin therapy caused an enhancement in the compensatory hippocampal neurogenesis and neurotrophic growth factors (e.g., doublecortin-1) and compensatory central anti-inflammatory cytokines. Our results indicate that melatonin attenuates the spatial memory and motor deficits via the modification of cortical and hippocampal dendritic spine morphology, hippocampal microgliosis and neurogenesis, and neuroinflammation in mice with traumatic brain injury.

Efficient photocatalytic inactivation of E. coli by Mn-CdS/ZnCuInSe/CuInS2 quantum dots-sensitized TiO2 nanowires.

A novel visible light-driven photocatalyst (represented as Mn-CdS/ZCISe/CIS/TiO2) for the passivation of E. coli was prepared with TiO2 nanowires as support and using CuInS2 (CIS) and ZnCuInSe (ZCISe) quantum dots (QDs), as well as Mn-doped CdS (Mn-CdS) nanoparticles (NPs) as sensitizers. The use of CIS and ZCISe QDs and Mn-CdS NPs extends the light harvest region to visible light. The photoelectric conversion efficiency was consequently improved, with a photocurrent density of 12.5 mA cm-2, about 60 times that of pure TiO2 nanowires. The germicidal efficiency of the photocatalyst was assessed by passivation of E. coli, 96% bacteria in 50 ml 105 colony forming units (CFU) ml-1 solution were killed within 50 min. Besides the high efficiency, the composite has good stability and satisfactory recycling performance. The antibiotic mechanism was also performed by using photoluminescence and a scavenging agent of different active matter, revealing that the photo-generated holes play a major role in the sterilization process.

Chinese Herbal Medicine Versus Placebo for the Treatment Of Chronic Obstructive Pulmonary Disease: A Protocol of Systematic Review and Meta-analysis.

BACKGROUND: Chinese herbal medicine (CHM) has been shown to be effective in the treatment of stable chronic obstructive pulmonary disease (COPD) by published meta-analyses. However, disease outcomes were inconsistent and heterogeneity was observed attributed to placebo-controlled studies. We present a protocol for a systematic review aiming to evaluate the clinical efficacy and safety of CHM comparing to placebo in the treatment of stable COPD, to provide robust evidence for the use of CHM in COPD. METHODS: We will comprehensively search the following 9 databases from inception to March 2019: Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), WANFANG Database, Chinese Scientific and Technological Periodical Database (VIP) and Chinese Biomedical Database (CBM), and the Cochrane Library database. All clinical randomized controlled trials comparing CHM to placebo for the treatment of stable COPD in English or Chinese will be included. The primary outcome will be quality of life, symptom score and exacerbation frequency, and the secondary outcomes include traditional Chinese medicine syndrome score and effective rate, lung function, 6-minute walk distance, and adverse events. Data extraction and quality assessment will be performed independently by 2 reviewers. Data synthesis and risk of bias will be assessed using the Review Manager software. This protocol will be conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidance. RESULTS: This systematic review and meta-analysis will provide a high-quality comprehensive evaluation of the efficacy and safety based on current literature evidence of CHM intervention for stable COPD. CONCLUSION: The conclusion of this study will present the evidence of whether CHM is an effective and safe intervention for stable COPD patients.

Acupuncture treatment of lung-spleen Qi deficiency in stable chronic obstructive pulmonary disease: a randomized, open-label, controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of acupuncture that reinforces the spleen to strengthen the lung in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: This was a randomized, open-controlled trial in which the acupuncturist and the participants were not blinded, but the outcome evaluators and data analysts were blinded. One-hundred-and-two patients with stable COPD were randomly divided into two groups in a 1∶1 ratio. The acupuncture group received 30-minute sessions of acupuncture therapy at the same acupoints three times weekly for 6 weeks in addition to routine conventional Western Medicine treatment; the control group received routine conventional Western Medicine treatment alone. The primary outcome was the Borg scale score, which was assessed immediately after the 6-minute walk test. The secondary outcomes were the 6-minute walk distance, lung function, and oxygen saturation. Measurements were obtained at baseline and after 6 weeks of treatment. RESULTS: After 6 weeks of treatment, the Borg scale score in the acupuncture group was significantly better than that in the control group (2.02 ± 0.71 versus 5.01 ± 0.34, P < 0.05). Furthermore, the post-treatment improvements in the 6-minute walk distance, lung function, and oxygen saturation were significantly greater in the acupuncture group than in the control group, showing that the acupuncture group had better exercise tolerance. CONCLUSION: The findings suggest that acupuncture that aims to reinforce the spleen to strengthen the lung is a safe and effective adjuvant therapy that effectively improves the exercise capacity of patients with stable COPD.

[Analysis on Randomized Controlled Trials for Acupuncture Treatment of Simple Obesity Collected from PubMed].

OBJECTIVE: To analyze studies published in journals included in PubMed in terms of randomized controlled trials (RCTs) examining the therapeutic effect of acupuncture for simple obesity, so as to provide a reference for subsequent RCT-related designs and results. METHODS: RCT literature about acupuncture treatment of simple obesity from the PubMed database and from 2000 to 2016 was retrieved by using keywords of "obesity" "fat" "acupuncture" "joint application of acupuncture and herbal medicine" or "auricular point" "electroacupuncture", "acupoint application", or "cupping", followed by screening, extraction and evaluation of the design methodology and outcomes using Consolidated Standards for Reporting of Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA). RESULTS: Fourteen articles from six countries in Asia examining the therapeutic effect of acupuncture in the treatment of simple obesity mainly by using acupoints of the Stomach Meridian were included. Generally, acupuncture was found to be more effective than sham acupuncture. However, PubMed did not include any RCTs comparing acupuncture with western medicine for weight loss and many problems (as details of needling manipulation, etc.) remained in the the research reports available in the database. CONCLUSION: All the existing RCTs generally affirm the positive efficacy of acupuncture for simple obesity, but high-quality RCTs, particularly those comparing acupuncture with western medicines for weight loss are lacking.

Identification of a Novel (-)-5-Epieremophilene Synthase from Salvia miltiorrhiza via Transcriptome Mining.

Salvia miltiorrhiza, a medicinal plant in China, has been used for thousands of years to treat coronary heart diseases. Although biosynthesis of tanshinones, a group of diterpenoids in S. miltiorrhiza, has been extensively investigated, to date we know little about the formation of monoterpenes and sesquiterpenes in this medicinal plant. Here, we report the characterization of three sesquiterpene synthases, named SmSTPS1, SmSTPS2, and SmSTPS3, which catalyzed the formation of a new compound, (-)-5-epieremophilene. Additionally, the (-)-5-epieremophilene biosynthesis activity of SmSTPS1 was confirmed by transient expression in Nicotiana benthamiana. Despite the similar enzyme activities of SmSTPS1, SmSTPS2, and SmSTPS3, the three (-)-5-epieremophilene synthase genes displayed different spatial expression patterns and responded differently to hormone treatments, implicating their specific roles in plant-environment interactions. Our results provide valuable data to understanding the biosynthesis and composition of terpenes in plant.

Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants.

Plants synthesize and accumulate large amount of specialized (or secondary) metabolites also known as natural products, which provide a rich source for modern pharmacy. In China, plants have been used in traditional medicine for thousands of years. Recent development of molecular biology, genomics and functional genomics as well as high-throughput analytical chemical technologies has greatly promoted the research on medicinal plants. In this article, we review recent advances in the elucidation of biosynthesis of specialized metabolites in medicinal plants, including phenylpropanoids, terpenoids and alkaloids. These natural products may share a common upstream pathway to form a limited numbers of common precursors, but are characteristic in distinct modifications leading to highly variable structures. Although this review is focused on traditional Chinese medicine, other plants with a great medicinal interest or potential are also discussed. Understanding of their biosynthesis processes is critical for producing these highly value molecules at large scale and low cost in microbes and will benefit to not only human health but also plant resource conservation.