Genome-Wide Identification and Characterization of the Salvia miltiorrhiza Histone Deacetylase (HDAC) Family in Response to Multiple Abiotic Stresses.

Salvia miltiorrhiza is a plant commonly used in traditional Chinese medicine. Its material bases for treating diseases are tanshinones and phenolic acids, including salvianolic acids. Histone deacetylase proteins (HDACs) are a class of specific functional enzymes that interact with acetylation groups on the N-terminal lysine of histone proteins further regulate gene transcription through structural changes at the chromatin level. HDACs involved in the growth and development of various plants, and induced by plant hormones to regulate the internal environment of plants to resist stress, at the same time affect the accumulation of some secondary metabolites. However, the role of SmHDACs on the accumulation of salvianolic acid in S. miltiorrhiza remains unclear. In this study, 16 SmHDACs genes were identified from the high-quality S. miltiorrhiza genome, their physicochemical properties were predicted. In phylogenetic trees co-constructed with HDACs proteins from other plants, SmHDACs was divided into three subfamilies, each with similar motif and conserved domain composition. The distribution of the three subfamilies is similar to that of dicotyledonous plants. Chromosome localization analysis showed that SmHDACs genes were randomly located. Cis-acting element analysis predicted that SmHDACs gene expression may be related to and induced by various phytohormones, such as MeJA and ABA. By combining the expression pattern and co-expression network induced by phytohormones, we speculate that SmHDACs may further influence the synthesis of salvianolic acid, and identified SmHDA5, a potential functional gene, then speculate its downstream target based on the co-expression network. In summary, we analyzed the SmHDACs gene family of S. miltiorrhiza and screened out the potential functional gene SmHDA5. From the perspective of epigenetics, we proposed the molecular mechanism of plant hormone promoting salvianolic acid synthesis, which filled the gap in the subdivision of histone deacetylase in S. miltiorrhiza research, provided a theoretical basis for the culture and transformation of S. miltiorrhiza germplasm resources.

Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy.

Flexible and stretchable heaters are increasingly recognized for their great potential in wearable thermotherapy to treat muscle spasms, joint injuries and arthritis. However, issues like lengthy processing, high fabrication cost, and toxic chemical involvement are obstacles on the way to popularize stretchable heaters for medical use. Herein, using a single-step customizable laser fabrication method, we put forward the design of cost-effective wearable laser-induced graphene (LIG) heaters with kirigami patterns, which offer multimodal stretchability and conformal fit to the skin around the human body. First, we develop the manufacturing process of the LIG heaters with three different kirigami patterns enabling reliable stretchability by out-of-plane buckling. Then, by adjusting the laser parameters, we confirm that the LIG produced by medium laser power could maintain a balance between mechanical strength and electrical conductivity. By optimizing cutting-spacing ratios through experimental measurements of stress, resistance and temperature profiles, as well as finite element analysis (FEA), we determine that a larger cutting-spacing ratio within the machining precision will lead to better mechanical, electrical and heating performance. The optimized stretchable heater in this paper could bear significant unidirectional strain over 100% or multidirectional strain over 20% without major loss in conductivity and heating performance. On-body tests and fatigue tests also proved great robustness in practical scenarios. With the advantage of safe usage, simple and customizable fabrication, easy bonding with skin, and multidirectional stretchability, the on-skin heaters are promising to substitute the traditional heating packs/wraps for thermotherapy.

The effect of Chinese herbal formulas combined with metformin on modulating the gut microbiota in the amelioration of type 2 diabetes mellitus: A systematic review and meta-analysis.

To assess and analyse the effectiveness and safety of combined Chinese herbal formula (CHF) and metformin treatment in the modulation of the gut microbiota in the amelioration of type 2 diabetes mellitus(T2DM), all publications addressing the effect of this combination treatment on the quantitative alterations in the gut microbiota and glucose parameters were collected. Rob tool in the Cochrane handbook was performed to evaluate the methodological quality of all included studies. Relevant information and statistics were abstracted and synthesized in Review Manager 5.4 to evaluate the efficacy of combination treatment. Sensitivity analyses and subgroup analyses were used to analyse the sources of heterogeneity. Publication bias analyses were performed by Stata software to assess the robustness and quality of the outcomes. As a result, a total of 12 eligible RCTs with 1307 T2DM participants from 7 electronic databases were included. Combined CHF with metformin treatment showed better efficacies than metformin monotherapy in regulating the structure of the gut microbiota, characterized by increased Bifidobacterium, Lactobacillus and Bacteroidetes and decreased Enterobacteriaceae, Enterococcus, and Saccharomyces along with better decreases in glycated haemoglobin, fasting plasma glucose, 2-hour postprandial blood glucose, fasting insulin and homeostasis model assessment of insulin resistance. Subgroup analyses further analysed the effect of metformin doses and CHF classifications on controlling hyperglycaemia and altering the gut microbiota. In conclusion, our meta-analysis suggested that combined CHF with metformin treatment is promising for the modulation of the gut microbiota along with ameliorating hyperglycemia in T2DM patients. Importantly, more well-designed RCTs are needed to validate the outcomes and verify the treatment value for clinical purposes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021291524, identifier CRD42021291524.

A new Desmodesmus sp. from the Tibetan Yamdrok Lake.

Revegetation of exposed sub-soil, while a desirable recovery strategy, often fails due to extreme soil chemical properties, such as low organic matter and pH levels. Microalgae play a key role in maintaining water quality in the lakes and rivers on the Qinghai-Tibet plateau. Plateau microalgae have extensive application prospects in environmental purification, biotechnology, medicine and cosmetics, food industry, and renewable energy. To identify the high biomass of microalgae present in nature, microalgae with the greatest biomass were screened from natural water samples through filtration, pre-culture, and plate scribing separation. Following identification via 18S rRNA sequencing as for the Desmodesmus sp., we constructed a neighbor-joining phylogenetic tree. The novel Desmodesmus sp. from the Tibetan Yamdrok Lake were identified through polyphasic taxonomy. Simultaneously, the sequence of the experimental samples and the target species were shown different following the identification and analysis of SNP and InDel loci. The light-absorbing properties of plateau Desmodesmus sp. have been investigated previously. The characteristic absorption peak of Desmodesmus sp. on the plateau was measured at 689 nm in the visible spectrum using full wavelength scanning with a UV-Vis spectrophotometer. For Desmodesmus sp. which is prone to settling in the process of amplification culture. By monitoring the change trend of total nitrogen, total phosphorus, pH and electrical conductivity in algae solution system, we determined that the logarithmic growth phase and the best transfer window of Desmodesmus sp. were at 15-20 days. This study can provide basic research methods for the study of microalgae in high altitude areas, and lay a foundation for the later study and application of microalgae.

pH-Triggered Size-Tunable Silver Nanoparticles: Targeted Aggregation for Effective Bacterial Infection Therapy.

The rapid spread of drug-resistant pathogens threatens human health. To address the current antibacterial dilemma, the development of antibiotic-free strategies using nanotechnology is imperative. In this study, silver nanoparticles (Ag-P&C NPs) with pH-sensitive charge reversal and self-aggregation capacities are successfully synthesized. In the acidic microenvironment of bacterial biofilms, protonation of the surface peptide enhances the affinity of Ag-P&C NPs for bacteria, which can make Ag-P&C NPs prone to target and penetrate into biofilms, and the self-aggregated capacity helps Ag-P&C NPs remain in biofilms for a long time to disrupt bacterial biofilm formation. In addition, biocompatible Ag-P&C NPs are utilized in three types of bacteria-infected animal models. They exhibit an excellent performance in killing bacteria, inhibiting plaque biofilms, and ameliorating inflammatory responses. In conclusion, this study offers new insights into antibiotic-free antibacterial strategies, and exhibits promising application prospects.

A prophylactic effect of aluminium-based adjuvants against respiratory viruses via priming local innate immunity.

Infection caused by respiratory viruses can lead to a severe respiratory disease and even death. Vaccination is the most effective way to prevent the disease, but it cannot be quickly applied when facing an emerging infectious disease. Here, we demonstrated that immunization with an aluminium-zinc hybrid particulate adjuvant (FH-001) alone, bearing great resemblance in morphology with commonly used aluminium-based adjuvants in vaccines, could quickly induce mice to generate a broadly protective immune response to resist the lethal challenge of influenza B viruses. Furthermore, a multi-omics-based analysis revealed that the alveolar macrophage and type I interferon pathway, rather than adaptive immunity and type II interferon pathway, were essential for the observed prophylactic effect of FH-001. More importantly, a similar protective effect was observed against influenza A virus strain A/Shanghai/02/2013(H7N9), A/California/04/2009(H1N1) and respiratory syncytial virus. Therefore, we introduced here a new and promising strategy that can be quickly applied during the outbreak of emerging respiratory viruses.

Intragenic heterochromatin-mediated alternative polyadenylation modulates miRNA and pollen development in rice.

Despite a much higher proportion of intragenic heterochromatin-containing genes in crop genomes, the importance of intragenic heterochromatin in crop development remains unclear. Intragenic heterochromatin can be recognised by a protein complex, ASI1-AIPP1-EDM2 (AAE) complex, to regulate alternative polyadenylation. Here, we investigated the impact of rice ASI1 on global poly(A) site usage through poly(A) sequencing and ASI1-dependent regulation on rice development. We found that OsASI1 is essential for rice pollen development and flowering. OsASI1 dysfunction has an important impact on global poly(A) site usage, which is closely related to heterochromatin marks. Intriguingly, OsASI1 interacts with the intronic heterochromatin of OsXRNL, a nuclear XRN family exonuclease gene involved in the processing of an miRNA precursor, to promote the processing of full-length OsXRNL and regulate miRNA abundance. We found that OsASI1-mediated regulation of pollen development partially depends on OsXRNL. Finally, we characterised the rice AAE complex and its involvement in alternative polyadenylation and pollen development. Our findings help to elucidate an epigenetic mechanism governing miRNA abundance and rice development, and provide a valuable resource for studying the epigenetic mechanisms of many important processes in crops.

Efficacy of aromatherapy on dental anxiety: A systematic review of randomised and quasi-randomised controlled trials.

OBJECTIVES: To evaluate the efficacy of aromatherapy on dental anxiety. METHODS: A detailed protocol was registered a priori (PROSPERO: CRD42019141093). PubMed, EMBASE, CDSR, CENTRAL, CNKI and grey literature databases were searched from inception to 10 January 2020. Randomised controlled trials (RCTs) and quasi-randomised controlled trials (CCTs) that examined the effects of aromatherapy on dental anxiety, compare to either negative control (i.e. no aromatherapy) or other positive control approaches (e.g. music), were included. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration's tool and ROBINS-I, while the certainty of evidence was assessed using GRADE. A narrative synthesis was performed, rather than meta-analysis, due to the high level of heterogeneity across studies. RESULTS: Eleven RCTs and six CCTs were included. The risk of bias was identified as either high or unclear in RCTs, and moderate to serious in CCTs. Performance bias and detection bias were the most prevalent in RCTs, followed by selection bias and reporting bias. As to CCTs, greater risk of bias was found in the selection of participants into the study and in the measurement of outcomes. Based on the selected studies, the most commonly used aromatherapy for dental anxiety management was lavender fragrance, followed by orange. Compared to the negative control condition, aromatherapy might reduce the anxiety-related physiological parameters and psychometric rating, pain, and mood, alertness, and calmness compared to the negative control condition; and there might be no intergroup difference in such outcomes between aromatherapy and music. However, GRADEs of the relevant evidence were judged as low to very low. CONCLUSIONS: Compared to the negative control condition, aromatherapy is more effective to reduce dental anxiety and has comparable effects on dental anxiety compared to music intervention; however, the certainty of evidence is relatively limited. Further high-quality randomised trials with robust study design and large sample size are warranted to confirm our findings and to confirm the role of aromatherapy in relieving dental anxiety.

Effects of Herbal Mouthwashes on Plaque and Inflammation Control for Patients with Gingivitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: The aim of this study was to evaluate the overall effects of herbal mouthwashes as supplements to daily oral hygiene on plaque and inflammation control compared with placebos and chlorhexidine (CHX) mouthwashes in the treatment of gingivitis. METHODS: PubMed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and grey literature databases were searched. Only randomised controlled trials (RCTs) comparing herbal mouthwashes with placebos or CHX in the daily oral hygiene of patient with gingivitis were included to compare the effect of different mouthwashes on plaque and inflammation control. RESULTS: A total of 13 studies satisfied the eligibility criteria, and 11 studies were included in meta-analyses. Significant differences were observed in favour of herbal mouthwashes compared with placebos in both plaque- and inflammation-related indices (Quigley-Hein Plaque Index, QHPI: WMD = -0.61, 95% CI (-0.80, -0.42), P < 0.001; Gingival Index, GI: -0.28 (-0.51, -0.06), P=0.01; Modified Gingival Index, MGI: -0.59 (-1.08, -0.11), P=0.02; Gingival Bleeding Index, GBI: -0.06 (-0.09, -0.04), P < 0.001). No significant difference was found between herbal and CHX mouthwashes. CONCLUSIONS: Herbal mouthwashes have potential benefits in plaque and inflammation control as supplements to the daily oral hygiene of patients with gingivitis. Although no difference was observed between herbal and CHX mouthwashes in the selected studies, further high-quality RCTs are needed for more firm support before advising patients with gingivitis about whether they can use herbal mouthwashes to substitute for CHX mouthwashes or not (PROSPERO registration number: CRD42019122841).

Dioscin improves postmenopausal osteoporosis through inducing bone formation and inhibiting apoptosis in ovariectomized rats.

Postmenopausal osteoporosis (PMO) has become a public health problem worldwide. Hormonal replacement therapy (HRT) is the most popular treatment for PMO at present, but the side effects, including increased risk of endometrial cancer and breast cancer, limit its clinical use. Therefore, finding a new medication with high efficiency and less side-effects is urgently required. Dioscin is the main ingredient of some medicinal plants such as Dioscorea nipponica Makino and Dioscorea zingiberensis Wrigh. It is reported that dioscin has anti-tumoral and anti-atherosclerotic activity as well as an inhibitory effect on hepatic fibrosis. In this study, the effects of dioscin on PMO were examined and the mechanisms were analyzed. The results indicated that the bone mineral density and ultimate load of PMO rats were increased after being treated with dioscin. H&E staining and immunohistochemical staining showed the bone trabeculae formation and bone differentiation of PMO rats were promoted by dioscin. Western blots revealed that dioscin could activate the PI3K/P38/AKT signaling pathway and inhibit the apoptosis signaling pathway in bone tissue cells of PMO rats. In addition, MTT assays showed that MC3T3-E1 cell viability could be improved by dioscin. These results suggest dioscin is a potential therapeutic reagent for osteoporosis and deserves further investigation.

Enhancement of marinacarboline A biosynthesis by optimizing the riboflavin supplement in marine derived Nocardiopsis flavescens CGMCC 4.5723.

OBJECTIVES: To improve the bioproductivity of secondary metabolites of marine derived Nocardiopsis flavescens CGMCC 4.5723 by enhancing its riboflavin supplement. RESULTS: The NfRibA, type II guanosine triphosphate (GTP) cyclohydrolase (GCH II) of Nocardiopsis flavescens CGMCC 4.5723, was biochemically identified and showed that NfRibA could efficiently catalyze the first step of riboflavin biosynthesis to hydrolyze GTP into 2, 5-diamino-6-ribosylamino-4(3H)-pyrimidinedione 5'-phosphate (DARPP) with Km value of 160.11 ± 26.81 µM in vitro. The overexpression of NfribA could obviously increase riboflavin bioproduction to the titers of 0.41 ± 0.19 mg/l by comparing with the wild type counterpart. Consequently, this rise of riboflavin bioproduction did not disturb the expression of genes involved in marinacarboline A biosynthesis, but could significantly enhance its bioproduction with the titer of 5.5 ± 0.17 mg/l through comparing with wild type control. CONCLUSIONS: Optimization of riboflavin supplement could be a new promising strategy in actinomycetic marinacarboline A exploitation.

From Golden Rice to aSTARice: Bioengineering Astaxanthin Biosynthesis in Rice Endosperm.

Carotenoids are important phytonutrients with antioxidant properties, and are widely used in foods and feedstuffs as supplements. Astaxanthin, a red-colored ketocarotenoid, has strong antioxidant activity and thus can benefit human health. However, astaxanthin is not produced in most higher plants. Here we report the bioengineering of astaxanthin biosynthesis in rice endosperm by introducing four synthetic genes, sZmPSY1, sPaCrtI, sCrBKT, and sHpBHY, which encode the enzymes phytoene synthase, phytoene desaturase, ß-carotene ketolase, and ß-carotene hydroxylase, respectively. Transgneic overexpression of two (sZmPSY1 and sPaCrtI), three (sZmPSY1, sPaCrtI and sCrBKT), and all these four genes driven by rice endosperm-specific promoters established the carotenoid/ketocarotenoid/astaxanthin biosynthetic pathways in the endosperm and thus resulted in various types of germplasm, from the yellow-grained ß-carotene-enriched Golden Rice to orange-red-grained Canthaxanthin Rice and Astaxanthin Rice, respectively. Grains of Astaxanthin Rice were enriched with astaxanthin in the endosperm and had higher antioxidant activity. These results proved that introduction of a minimal set of four transgenes enables de novo biosynthesis of astaxanthin in the rice endosperm. This work provides a successful example for synthetic biology in plants and biofortification in crops; the biofortified rice products generated by this study could be consumed as health-promoting foods and processed to produce dietary supplements.

Panax quinquefolius saponin inhibits endoplasmic reticulum stress-mediated apoptosis and neurite injury and improves functional recovery in a rat spinal cord injury model.

The treatment goal in spinal cord injury (SCI) is to repair neurites and suppress cell apoptosis. Panax quinquefolius saponin (PQS) is the major active ingredient of American ginseng and has been demonstrated to have anti-inflammatory and anti-apoptotic roles in various diseases. However, the potential effect of PQS on the pathological process of acute SCI remains unknown. This work tested the effects of PQS on acute SCI and clarified its potential mechanisms. PQS treatment ameliorated the damage to spinal tissue and improved the functional recovery after SCI. PQS treatment inhibited endoplasmic reticulum (ER) stress and the associated apoptosis after acute SCI. PQS further abolished the triglyceride (TG)-induced ER stress and associated apoptosis in neuronal cultures. PQS appears to inhibit the ER-stress-induced neurite injury in PC12 cells. Our results suggest that PQS is a novel therapeutic agent for acute central nervous system injury.

20(s)-Protopanaxadiol (PPD) increases the radiotherapy sensitivity of laryngeal carcinoma.

Laryngeal carcinoma (LC) is one of the most prevalent malignant tumors in the head and neck area. Due to its high morbidity and mortality, LC poses a serious threat to human life and health. Even with surgical removal, some patients were not sensitive to radiotherapy or experienced transfer or recurrence. 20(s)-Protopanaxadiol (PPD), a natural product from Panax ginseng, has been reported to have cytotoxic effects against several cancer cell lines. However, whether it can improve the radiation sensitivity and the underlying mechanism of PPD's sensitization effect is still unknown. Herein, from in vitro and in vivo experiments, we found that the combination of PPD and radiation not only significantly inhibited proliferation and induced apoptosis, but also suppressed the tumor growth in mouse models. These findings confirmed the role of PPD in enhancing the sensitivity of radiotherapy. Moreover, our work showed that the expression levels of mTOR and its downstream effectors decreased remarkably after PPD addition when compared to radiation only. This result suggested that PPD's excellent synergistic effects with radiation might be associated with the down-regulation of the mTOR signaling pathway in Hep-2 cells.

A novel azulenyl nitrone antioxidant protects against MPTP and 3-nitropropionic acid neurotoxicities.

Oxidative stress plays an important role in neuronal death in neurodegenerative disorders such as Parkinson's disease (PD) and Huntington's disease (HD). Animal models of PD or HD, produced by administration of the mitochondrial toxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 3-nitropropionic acid (3NP), respectively, show increased free radical generation. Free radicals generated in biological systems can react with spin-trapping compounds, such as nitrones, to form stable adducts. In recent years, the utility of nitrones has moved beyond analytical applications and into the realm of neuroprotection as antioxidants in both brain ischemia and models of neurodegenerative diseases. In the present study, we administered a new nitrone antioxidant, stilbazulenyl nitrone (STAZN), with either MPTP or 3NP. STAZN attenuated MPTP-induced striatal dopamine depletion by 40% and showed a tendency to dose-dependent neuroprotection. STAZN dose-dependently protected against loss of tyrosine hydroxylase immunoreactive neurons in the substantia nigra pars compacta. STAZN reduced the striatal lesion volume caused by systemic 3NP administration from 44 +/- 9 to 20 +/- 6 mm(3). The lipid peroxidation marker, malondialdehyde(MDA), was significantly increased in the striatum, cortex, and cerebellum of rats after administration of 3NP. These increases were blocked by co-injection of STAZN. Our data provide further evidence that STAZN is a neuroprotective free radical spin trap, and suggest that the development of new antioxidants will broaden our therapeutic strategies for neurodegenerative diseases.