Genomic analysis of PIN-FORMED genes reveals the roles of SmPIN3 in root architecture development in Salvia miltiorrhiza.

Salvia miltiorrhiza is a widely utilized medicinal herb in China. Its roots serve as crucial raw materials for multiple drugs. The root morphology is essential for the quality of this herb, but little is known about the molecular mechanism underlying the root development in S. miltiorrhiza. Previous study reveals that the polar auxin transport is critical for lateral root development in S. miltiorrhiza. Whether the auxin efflux carriers PIN-FORMEDs (PINs) are involved in this process is worthy investigation. In this study, we identified nine SmPIN genes in S. miltiorrhiza, and their chromosome localization, physico-chemical properties, and phylogenetic relationship were analyzed. SmPINs were unevenly distributed across four chromosomes, and a variety of hormone responsive elements were detected in their promoter regions. The SmPIN proteins were divided into three branches according to the phylogenetic relationship. SmPINs with close evolutionary distance showed similar conserved motif features. The nine SmPINs showed distinct tissue-specific expression patterns and most of them were auxin-inducible genes. We generated SmPIN3 overexpression S. miltiorrhiza seedlings to investigate the function of SmPIN3 in the root development in this species. The results demonstrated that SmPIN3 regulated the root morphogenesis of S. miltiorrhiza by simultaneously affecting the lateral root development and the root anatomical structure. The root morphology, patterns of root xylem and phloem as well as the expressions of genes in the auxin signaling pathway all altered in the SmPIN3 overexpression lines. Our findings provide new insights for elucidating the regulatory roles of SmPINs in the auxin-mediated root development in S. miltiorrhiza.

Comprehensive Characterization of Triterpene Saponins in Rhizoma Panacis Japonici by Offline Two-Dimensional Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry.

Rhizoma Panacis Japonici (RPJ) is an ancient herbal medicine from China that has long been employed for its medicinal benefits in relieving arthritis physical debility and diverse afflictions. The primary bioactive constituents found in RPJ are triterpene saponins, which exhibit numerous pharmacological actions, including anti-inflammatory, antioxidant, and immunomodulating effects. The present study established a straightforward and effective approach for characterizing triterpene saponins in RPJ. An offline HILIC × RP LC/QTOF-MS method was developed, along with a self-constructed in-house database containing 612 saponins reported in the Panax genus and 228 predicted metabolites. The approach achieved good chromatographic performance in isolating triterpene saponins of RPJ, with the HILIC column as the first dimension (1D) and the BEH C18 column as the second dimension (2D). The developed two-dimensional liquid chromatography system exhibited an orthogonality of 0.61 and a peak capacity of 1249. Detection was performed using a QTOF mass spectrometer in a data-independent manner (MSE) in a negative ion mode. Using the in-house database, the collected MS data were processed by an automatic workflow on UNIFI 1.8.2 software, which included data correction, matching of precursor and product ions, and peak annotation. In this study, 307 saponins were characterized from RPJ and 76 saponins were identified for the first time in Panax japonicus. This research not only enhances our understanding of the chemical characteristics of RPJ but also offers a simple and efficient method for analyzing the complex composition of herbal medicine.

Potentiation of prefrontal cortex dopamine function by the novel cognitive enhancer d-govadine.

Cognitive impairment is a debilitating feature of psychiatric disorders including schizophrenia, mood disorders and substance use disorders for which there is a substantial lack of effective therapies. d-Govadine (d-GOV) is a tetrahydroprotoberberine recently shown to significantly enhance working memory and behavioural flexibility in several prefrontal cortex (PFC)-dependent rodent tasks. d-GOV potentiates dopamine (DA) efflux in the mPFC and not the nucleus accumbens, a unique pharmacology that sets it apart from many dopaminergic drugs and likely contributes to its effects on cognitive function. However, specific mechanisms involved in the preferential effects of d-GOV on mPFC DA function remain to be determined. The present study employs brain dialysis in male rats to deliver d-GOV into the mPFC or ventral tegmental area (VTA), while simultaneously sampling DA and norepinephrine (NE) efflux in the mPFC. Intra-PFC delivery or systemic administration of d-GOV preferentially potentiated medial prefrontal DA vs NE efflux. This differential effect of d-GOV on the primary catecholamines known to affect mPFC function further underscores its specificity for the mPFC DA system. Importantly, the potentiating effect of d-GOV on mPFC DA was disrupted when glutamatergic transmission was blocked in either the mPFC or the VTA. We hypothesize that d-GOV acts in the mPFC to engage the mesocortical feedback loop through which prefrontal glutamatergic projections activate a population of VTA DA neurons that specifically project back to the PFC. The activation of a PFC-VTA feedback loop to elevate PFC DA efflux without affecting mesolimbic DA release represents a novel approach to developing pro-cognitive drugs.

Differential patterns of basal and naloxone-evoked dopamine efflux in the rat dorsal and ventral striatum following prolonged-intermittent exposure to morphine.

Hypodopaminergia in the ventral striatum is a putative neurobiological correlate of withdrawal in opioid-dependent individuals. This perspective stands in contrast to brain imaging studies with chronic opioid users showing that naloxone-enhanced dopamine (DA) release in the dorsal striatum is positively correlated with withdrawal aversion. Here, we examined regional differences in striatal DA function associated with opioid withdrawal in rats exposed to intermittent morphine injections for 31 days. Basal concentrations of DA were reduced (i.e., indicating a hypodopaminergic state) in the ventral striatum on Day 10 of morphine exposure, whereas a more prolonged period of morphine treatment was required to reveal hypodopaminergia in the dorsal striatum on Day 31. The ventral striatum consistently exhibited naloxone-induced transient reductions in DA below the hypodopaminergic basal levels, whereas morphine enhanced DA efflux. In the dorsal striatum, DA responsivity to naloxone shifted from a significant decrease on Day 10 to a notable increase above hypodopaminergic basal levels on Day 31, corroborating the findings in the human dorsal striatum. Unexpectedly, the magnitude of morphine-evoked increases in DA efflux on Day 31 was significantly blunted relative to values on Day 10. These findings indicate that prolonged-intermittent access to morphine results in a sustained hypodopaminergic state as reflected in basal levels in the striatum, which is accompanied by regional differences in DA responsivity to naloxone and morphine. Overall, our findings suggest that prolonging the duration of morphine exposure to 31 days is sufficient to reveal neuroadaptations that may underlie the transition from initial drug exposure to opioid dependence.

Buyang Huanwu Decoction promotes neurovascular remodeling by modulating astrocyte and microglia polarization in ischemic stroke rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu Decoction (BYHWD), one of the most commonly utilized traditional Chinese medicine prescription for treatment of cerebral ischemic stroke. However, the understanding of BYHWD on neurovascular repair following cerebral ischemia is so far limited. AIM OF THE STUDY: This research investigated the influence of BYHWD on neurovascular remodeling by magnetic resonance imaging (MRI) technology and revealed the potential neurovascular repair mechanism underlying post-treatment with BYHWD after ischemic stroke. MATERIALS AND METHODS: Male Sprague-Dawley rats were utilized as an ischemic stroke model by permanent occlusion of the middle cerebral artery (MCAO). BYHWD was intragastrically administrated once daily for 30 days straight. Multimodal MRI was performed to detect brain tissue injuries, axonal microstructural damages, cerebral blood flow and intracranial vessels on the 30th day after BYHWD treatment. Proangiogenic factors, axonal/synaptic plasticity-related factors, energy transporters and adenosine monophosphate-activated protein kinase (AMPK) signal pathway were evaluated using western blot. Double immunofluorescent staining and western blot were applied to evaluate astrocytes and microglia polarization. RESULTS: Administration of BYHWD significantly alleviated infarct volume and brain tissue injuries and ameliorated microstructural damages, accompanied with improved axonal/synaptic plasticity-related factors, axonal growth guidance factors and decreased axonal growth inhibitors. Meanwhile, BYHWD remarkably improved cerebral blood flow, cerebral vascular signal and promoted the expression of proangiogenic factors. Particularly, treatment with BYHWD obviously suppressed astrocytes A1 and microglia M1 polarization accompanied with promoted astrocyte A2 and microglia M2 polarization. Furthermore, BYHWD effectively improved energy transporters. Especially, BYHWD markedly increased expression of phosphorylated AMPK, cyclic AMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) accompanied by inactivation of the NF-κB. CONCLUSION: Taken together, these findings identified that the beneficial roles of BYHWD on neurovascular remodeling were related to AMPK pathways -mediated energy transporters and NFκB/CREB pathways.

Synthesis and catalytic activity of tetradentate ß-diketiminato rare-earth metal monoalkyl complexes in tandem Oppenauer oxidation and cross-aldol condensation.

A series of unsymmetric tetradentate ß-diketiminato rare-earth metal monoalkyl complexes were synthesized, and their catalytic behavior has been well developed. Indole-incorporated ß-diketiminato proligands H2L (L = MeC(NDipp)CHC(Me)NCH2CH2-3-(1-R-C8H4N), R = CH2-(2-C4H7O), L1; R = (CH2)2OMe, L2; Dipp = 2,6-iPr2C6H3) were prepared by the reaction of an arylamino-enone with 1-substituted-tryptamine in good yields. Treatment of the proligands with the rare-earth metal trialkyl complexes RE(CH2SiMe3)3(THF)2 generated the corresponding unsymmetric N,N,C,O-tetradentate ß-diketiminato rare-earth metal monoalkyl complexes LRE(CH2SiMe3) (L1, RE = Y (1a), Gd (1b), Yb (1c), Lu (1d); L2, RE = Y (2a), Gd (2b), Yb (2c), and Lu(2d)). During the process, the activation of the sp2 C-H bond at the 2-position of the indole ring led to the formation of an unprecedented ß-diketiminato dianion L2-, bonding to the rare-earth metal ions in a chelating N,N,C,O-tetradentate manner. Further studies indicated that these tetradentate rare-earth metal complexes could initiate the Oppenauer oxidation of secondary alcohols into the corresponding ketones in high yields. In the case of primary alcohols, a tandem Oppenauer oxidation and cross-aldol condensation occurred unexpectedly. Various α-mono-substituted benzylidene acetones, α,α'-bis-substituted benzylidene acetones and cyclohexanones were obtained under mild conditions only by controlling the molar ratio of alcohols to ketones. Notably, all these alkenylation ketones exhibited exclusive E configuration.

Therapeutic effect of the total saponin from Panax Japonicus on experimental autoimmune encephalomyelitis by attenuating inflammation and regulating gut microbiota in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizomes of Panax japonicus (RPJ), a traditional herbal medicine, was used for treating arthritis and physical weakness in China from the Ming dynasty. Triterpene saponins are the main bioactive components of RPJ. In this work, for the first time, we evaluate the therapeutic effect of the total saponin from RPJ (TSPJ) on experimental autoimmune encephalomyelitis (EAE) mice induced by myelin oligodendrocyte glycoprotein (MOG) 35-55, a commonly used animal model of Multiple sclerosis (MS). AIM OF THE STUDY: To evaluate the therapeutic effect of TSPJ on EAE and explored its possible underlying mechanisms. MATERIALS AND METHODS: EAE was induced by MOG 35-55. Mice were administrated with TSPJ (36.5 mg/kg, 73 mg/kg) and prednisone acetate (positive control) orally once daily up to 28 days postimmunization, and their neurological deficit was scored. Hematoxylin and Eosin (HE), Luxol Fast Blue (LFB), and transmission electron microscopy (TEM) were carried out to evaluate the EAE-induced pathological changes in the brain and spinal cord. IL-17a and Foxp3 levels in central nervous system (CNS)were evaluated by immunohistochemical staining. The changes in IL-1ß, IL-6, and TNF-α levels in serum and CNS were measured with ELISA. Quantitative reverse transcription PCR (qRT-PCR) was used to access mRNA expression in CNS of the above indices. The percentages of Th1, Th2, Th17and Treg cells in spleen were determined by Flow Cytometry (FCM). Furthermore, 16S rDNA sequencing was used to detect the intestinal flora of mice in each group. In vitro studies, lipopolysaccharides (LPS)-induced BV2 microglia cells were used and the expression of TLR4, MyD88, p65, and p-p65 in cells was detected by Western blot. RESULTS: TSPJ treatment significantly alleviated neurological impairment caused by EAE. Histological examination confirmed the protective effects of TSPJ on myelin sheath and the reduction of inflammatory cell infiltration in the brain and spinal cord of EAE mice. TSPJ notably downregulated the ratio of IL-17a/Foxp3 at protein and mRNA levels in CNS, as well as Th17/Treg and Th1/Th2 cell ratios in the spleen of EAE mice. The levels of TNF-α, IL-6, and IL-1ß in CNS and peripheral serum also decreased post-TSPJ treatment. In vitro, TSPJ suppressed LPS-induced production of inflammatory factors in BV2 cells via TLR4-MyD88-NF-κB signaling pathway. More importantly, TSPJ interventions altered the composition of gut microbiota and restored the ratio of Firmicutes to Bacteroidetes in EAE mice. Furthermore, Spearman's correlation analysis revealed that a relationship existed between statistically significantly altered genera and CNS inflammatory indices. CONCLUSION: Our results demonstrated TSPJ had therapeutic effects on EAE. Its anti-neuroinflammation property in EAE was related to modulating gut microbiota and inhibiting TLR4-MyD88-NF-κB signaling pathway. Our study indicated that TSPJ may be a potential candidate for the treatment of MS.

Influenza vaccine hesitancy and influencing factors among university students in China: a multicenter cross-sectional survey.

AIM: Highly mutable and contagious influenza poses a serious health threat to university students and their close contacts. Although annual influenza vaccination is an effective way to prevent influenza, influenza vaccination rates among Chinese university students are still low due to vaccine hesitancy. This study investigated Chinese university students' hesitancy to receive influenza vaccine and its influencing factors during the COVID-19 pandemics based on WHO's vaccine hesitancy matrix. METHODS: A multicenter cross-sectional study of university students in four cities across China was conducted via a web-based questionnaire in June 2022. Binary logistic regression was adopted to determine the factors around contextual influences, individual and group influences, and vaccines/vaccination specific issues. The reliability and validity of the questionnaire were good, with a Kronbach alpha coefficient of 0.892 and a KMO coefficient of 0.957. RESULTS: Of the 2261 Chinese university students surveyed, 44.7% had influenza vaccine hesitancy. Binary logistic regression showed that students considering high severity (OR = 0.946) or probability (OR = 0.942) of getting influenza, trusting vaccine-related advice from medical personnel (OR = 0.495) had lower odds of hesitancy. The odds of influenza vaccine hesitancy were higher if the students believed that vaccination was not necessary (OR = 4.040), had not been recommended by people around (OR = 1.476) and had no previous vaccinations or appointments (OR = 2.685). CONCLUSIONS: Medical staff are suggested to provide health education, improve doctor-patient communication and recommend vaccinations to university students to increase their risk perception and willingness to get an influenza vaccination. Collective vaccination strategies can be implemented to reduce the vaccine hesitancy for students.

Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification.

Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has shown outstanding efficacy in treating stroke. This study investigated various therapeutic targets of HSHS for ischemic stroke using mRNA transcriptomics. Herein, rats were randomly separated into the sham, model, HSHS 5.25 g/kg (HSHS5.25), and HSHS 10.5 g/kg (HSHS10.5) groups. Rats suffering from stroke were induced by permanent middle cerebral artery occlusion (pMCAO). After seven days of HSHS treatment, behavioral tests were conducted, and histological damage was examined with hematoxylin-eosin (HE). The mRNA expression profiles were identified using microarray analysis and quantitative real-time PCR (qRT-PCR) validated gene expression changes. An analysis of gene ontology and pathway enrichment was conducted to analyze potential mechanisms confirmed using immunofluorescence and western blotting. HSHS5.25 and HSHS10.5 improved neurological deficits and pathological injury in pMCAO rats. The intersections of 666 differentially expressed genes (DEGs) were chosen using transcriptomics analysis in the sham, model, and HSHS10.5 groups. The enrichment analysis suggested that the therapeutic targets of HSHS might regulate the apoptotic process and ERK1/2 signaling pathway, which was related to neuronal survival. Moreover, TUNEL and immunofluorescence analysis indicated that HSHS inhibited apoptosis and enhanced neuronal survival in the ischemic lesion. Western blot and immunofluorescence assay indicated that HSHS10.5 decreased Bax/Bcl-2 ratio and suppressed caspase-3 activation, while the phosphorylation of ERK1/2 and CREB was upregulated in a stroke rat model after HSHS treatment. Effective inhibition of neuronal apoptosis by activating the ERK1/2-CREB signaling pathway may be a potential mechanism for HSHS in the treatment of ischemic stroke.

Airborne antibiotic resistome and human health risk in railway stations during COVID-19 pandemic.

Antimicrobial resistance is recognized as one of the greatest public health concerns. It is becoming an increasingly threat during the COVID-19 pandemic due to increasing usage of antimicrobials, such as antibiotics and disinfectants, in healthcare facilities or public spaces. To explore the characteristics of airborne antibiotic resistome in public transport systems, we assessed distribution and health risks of airborne antibiotic resistome and microbiome in railway stations before and after the pandemic outbreak by culture-independent and culture-dependent metagenomic analysis. Results showed that the diversity of airborne antibiotic resistance genes (ARGs) decreased following the pandemic, while the relative abundance of core ARGs increased. A total of 159 horizontally acquired ARGs, predominantly confering resistance to macrolides and aminoglycosides, were identified in the airborne bacteria and dust samples. Meanwhile, the abundance of horizontally acquired ARGs hosted by pathogens increased during the pandemic. A bloom of clinically important antibiotic (tigecycline and meropenem) resistant bacteria was found following the pandemic outbreak. 251 high-quality metagenome-assembled genomes (MAGs) were recovered from 27 metagenomes, and 86 genera and 125 species were classified. Relative abundance of ARG-carrying MAGs, taxonomically assigned to genus of Bacillus, Pseudomonas, Acinetobacter, and Staphylococcus, was found increased during the pandemic. Bayesian source tracking estimated that human skin and anthropogenic activities were presumptive resistome sources for the public transit air. Moreover, risk assessment based on resistome and microbiome data revealed elevated airborne health risks during the pandemic.

Enhanced Cycling Performance of All-Solid-State Li-S Battery Enabled by PVP-Blended PEO-Based Double-Layer Electrolyte.

Despite the high specific capacity of Li-S battery, shuttle effect of lithium polysulfides (LiPSs) and safety issue pose a great challenge to realize its commercial application. Replacing liquid electrolyte with poly (ethylene oxide) (PEO) -based solid-state electrolyte is considered as a promising method to boost the safety, but the shuttle effect of LiPSs cannot be completely eliminated. In this work, a new kind of double-layer PEO-based polymer electrolyte is designed to restrict the LiPSs. The layer next to cathode consists of PEO and poly(vinylpyrrolidone) (PVP). The other layer consists of PEO. PVP with abundant of amide groups has been proved to have strong affinity to LiPSs. The strong interaction between LiPSs and carbonyl groups in amide is verified by Attenuated Total Reflection-Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy tests. As a result, the assembled Li-S battery exhibits a specific capacity of 1100 mAh g-1 and capacity retention of 347 mAh g-1 after 200 cycles at 60 °C and 0.05 C, while the capacity retention of the battery without PVP-blended PEO electrolyte remains only 27 % at the same conditions.

Identification and Quantification of Bu Shen Yi Sui Capsule by UPLC-LTQ-Orbitrap-MSn and UPLC-QTOF-MS/MS.

Traditional Chinese medicines (TCMs) have been considered as important alternative therapeutics because of their significant medicinal benefits in specific diseases. Chinese herb formula is characterized by a vast molecule that differs in routine medicines. Due to TCMs chemical complexity, proper quality control has been a great challenge. Choosing the appropriate method to identify and qualify these compounds is an important work to ensure its safety, efficacy and quality control. Thus, this study aimed at providing novel information on high-resolution LTQ-Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap-MSn) based identification of Bu Shen Yi Sui capsule (BSYSC), which is used in treating multiple sclerosis as a kind of TCMs. Under the proposed chromatographic conditions, 80 chemical components classified as anthraquinone, phenolic acid and phenylethanoid glycosides were separated and identified from BSYSC. Coupled with the high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) method, eight of them were regarded as marker compounds for the quantitative evaluation of BSYSC. The identification and quantification with precision of UPLC-LTQ-Orbitrap-MSn and UPLC-QTOF-MS/MS could facilitate essential data for further pharmacokinetic studies of BSYSC.

Spread of airborne antibiotic resistance from animal farms to the environment: Dispersal pattern and exposure risk.

Animal farms have been considered as the critical reservoir of antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB). Spread of antibiotic resistance from animal farms to the surrounding environments via aerosols has become a growing concern. Here we investigated the dispersal pattern and exposure risk of airborne ARGs (especially in zoonotic pathogens) in the environment of chicken and dairy farms. Aerosol, dust and animal feces samples were collected from the livestock houses and surrounding environments (upwind and downwind areas) for assessing ARG profiles. Antibiotic resistance phenotype and genotype of airborne Staphylococcus spp. was especially analyzed to reveal the exposure risk of airborne ARGs. Results showed that airborne ARGs were detected from upwind (50 m/100 m) and downwind (50 m/100 m/150 m) air environment, wherein at least 30% of bacterial taxa dispersed from the animal houses. Moreover, atmospheric dispersion modeling showed that airborne ARGs can disperse from the animal houses to a distance of 10 km along the wind direction. Clinically important pathogens were identified in airborne culturable bacteria. Genus of Staphylococcus, Sphingomonas and Acinetobacter were potential bacterial host of airborne ARGs. Airborne Staphylococcus spp. were isolated from the environment of chicken farm (n = 148) and dairy farm (n = 87). It is notable that all isolates from chicken-related environment were multidrug-resistance (>3 clinical-relevant antibiotics), with more than 80% of them carrying methicillin resistance gene (mecA) and associated ARGs and MGEs. Presence of numerous ARGs and diverse pathogens in dust from animal houses and the downwind residential areas indicated the accumulation of animal feces origin ARGs in bioaerosols. Employees and local residents in the chick farming environment are exposed to chicken originated ARGs and multidrug resistant Staphylococcus spp. via inhalation. This study highlights the potential exposure risks of airborne ARGs and antibiotic resistant pathogens to human health.

Anthropogenic activities and seasonal properties jointly drive the assemblage of bacterial communities in subtropical river basins.

Anthropogenic activities have inevitably impacted riverine ecosystems, yet their overall contribution to the assemblage of bacterial communities at a large river basin scale remains unclear. In this study, 16S amplicon sequencing was implemented to investigate the bacterial ecosystems in paired water and sediment of North River and West River basins in South China., which contains various anthropogenic environments (e.g., rural/urban area, mining area and livestock area). Subsequently, the links between bacterial community and various types of emerging pollutants in river water were analyzed. The results show that the bacterial assemblage of water and sediment had their own properties that the bacterial community of sediment were mainly affected by seasonal properties, while the bacterial community of water were affected by both seasons and anthropogenic activities. Therein, the aquatic bacterial compositions and abundances were driven by changes in temperature, dissolved oxygen and the emerging pollutants. The dominant phyla Proteobacteria and Firmicutes exhibited adaptability to the mining-affected regions, therein many clades (e.g., Beijerinckiaceae, Acetobacteraceae and Mycobacteriaceae) were also prevalent in the livestock-affected and densely-populated regions. In addition, these two phyla presented associations to the antibiotic resistance in water. The levels of antibiotics, relative antibiotic resistance gens (ARGs) and non-antibiotic pharmaceuticals (NAPs) were closely related to bacterial community composition, diversity and functional diversity, indicating their drive in shifting bacterial communities. Collectively, this work provides a basis for understanding the contribution of anthropogenic activities in shifting bacterial community at a large river basin scale. Further, the results provide new insights for expansion of ecological assessment.

Effect of Neurorepair for Motor Functional Recovery Enhanced by Total Saponins From Trillium tschonoskii Maxim. Treatment in a Rat Model of Focal Ischemia.

Trillium tschonoskii Maxim. (TTM), is a perennial herb from Liliaceae, that has been widely used as a traditional Chinese medicine treating cephalgia and traumatic hemorrhage. The present work was designed to investigate whether the total saponins from Trillium tschonoskii Maxim. (TSTT) would promote brain remodeling and improve gait impairment in the chronic phase of ischemic stroke. A focal ischemic model of male Sprague-Dawley (SD) rats was established by permanent middle cerebral artery occlusion (MCAO). Six hours later, rats were intragastrically treated with TSTT (120, 60, and 30 mg/kg) and once daily up to day 30. The gait changes were assessed by the CatWalk-automated gait analysis system. The brain tissues injuries, cerebral perfusion and changes of axonal microstructures were detected by multimodal magnetic resonance imaging (MRI), followed by histological examinations. The axonal regeneration related signaling pathways including phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3)/collapsin response mediator protein-2 (CRMP-2) were measured by western blotting. TSTT treatment significantly improved gait impairment of rats. MRI analysis revealed that TSTT alleviated tissues injuries, significantly improved cerebral blood flow (CBF), enhanced microstructural integrity of axon and myelin sheath in the ipsilesional sensorimotor cortex and internal capsule. In parallel to MRI findings, TSTT preserved myelinated axons and promoted oligodendrogenesis. Specifically, TSTT interventions markedly up-regulated expression of phosphorylated GSK-3, accompanied by increased expression of phosphorylated PI3K, AKT, but reduced phosphorylated CRMP-2 expression. Taken together, our results suggested that TSTT facilitated brain remodeling. This correlated with improving CBF, encouraging reorganization of axonal microstructure, promoting oligodendrogenesis and activating PI3K/AKT/GSK-3/CRMP-2 signaling, thereby improving poststroke gait impairments.

Effects of Light on Secondary Metabolite Biosynthesis in Medicinal Plants.

Secondary metabolites (SMs) found in medicinal plants are one of main sources of drugs, cosmetics, and health products. With the increase in demand for these bioactive compounds, improving the content and yield of SMs in medicinal plants has become increasingly important. The content and distribution of SMs in medicinal plants are closely related to environmental factors, especially light. In recent years, artificial light sources have been used in controlled environments for the production and conservation of medicinal germplasm. Therefore, it is essential to elucidate how light affects the accumulation of SMs in different plant species. Here, we systematically summarize recent advances in our understanding of the regulatory roles of light quality, light intensity, and photoperiod in the biosynthesis of three main types of SMs (polyphenols, alkaloids, and terpenoids), and the underlying mechanisms. This article provides a detailed overview of the role of light signaling pathways in SM biosynthesis, which will further promote the application of artificial light sources in medicinal plant production.

Tribo-electrochemistry induced artificial solid electrolyte interface by self-catalysis.

Potassium (K) metal is a promising alkali metal anode for its high abundance. However, dendrite on K anode is a serious problem which is even worse than Li. Artificial SEI (ASEI) is one of effective routes for suppressing dendrite. However, there are still some issues of the ASEI made by the traditional methods, e.g. weak adhesion, insufficient/uneven reaction, which deeply affects the ionic diffusion kinetics and the effect of inhibiting dendrites. Herein, through a unique self-catalysis tribo-electrochemistry reaction, a continuous and compact protective layer is successfully constructed on K metal anode in seconds. Such a continuous and compact protective layer can not only improve the K+ diffusion kinetics, but also strongly suppress K dendrite formation by its hard mechanical properties derived from rigid carbon system, as well as the improved K+ conductivity and lowered electronic conductivity from the amorphous KF. As a result, the potassium symmetric cells exhibit stable cycles last more than 1000 h, which is almost 500 times that of pristine K.

Ni2P nanocrystals embedded Ni-MOF nanosheets supported on nickel foam as bifunctional electrocatalyst for urea electrolysis.

It's highly desired but challenging to synthesize self-supporting nanohybrid made of conductive nanoparticles with metal organic framework (MOF) materials for the application in the electrochemical field. In this work, we report the preparation of Ni2P embedded Ni-MOF nanosheets supported on nickel foam through partial phosphidation (Ni2P@Ni-MOF/NF). The self-supporting Ni2P@Ni-MOF/NF was directly tested as electrode for urea electrolysis. When served as anode for urea oxidation reaction (UOR), it only demands 1.41 V (vs RHE) to deliver a current of 100 mA cm-2. And the overpotential of Ni2P@Ni-MOF/NF to reach 10 mA cm-2 for hydrogen evolution reaction HER was only 66 mV, remarkably lower than Ni2P/NF (133 mV). The exceptional electrochemical performance was attributed to the unique structure of Ni2P@Ni-MOF and the well exposed surface of Ni2P. Furthermore, the Ni2P@Ni-MOF/NF demonstrated outstanding longevity for both HER and UOR. The electrolyzer constructed with Ni2P@Ni-MOF/NF as bifunctional electrode can attain a current density of 100 mA cm-2 at a cell voltage as low as 1.65 V. Our work provides new insights for prepare MOF based nanohydrid for electrochemical application.

Trillium tschonoskii rhizomes' saponins induces oligodendrogenesis and axonal reorganization for ischemic stroke recovery in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Trillium tschonoskii Maxim. is one of traditional Chinese medical herbs that has been utilized to treat brain damages and cephalalgia. The neuroprotective effect of total saponins from Trillium tschonoskii rhizome (TSTT) has been demonstrated efficacy in rats following ischemia. However, the axonal remodeling effect of TSTT and the detailed mechanisms after ischemic stroke have not been investigated. AIM OF THE STUDY: We aimed to estimate therapeutic role of TSTT in axonal remodeling using magnetic resonance imaging (MRI) technique, and explored possible mechanisms underlying this process followed by histological assays in ischemic rats. METHODS: Male Sprague-Dawley (SD) rats underwent permanently focal cerebral ischemia induced by occluding right permanent middle cerebral artery. TSTT was intragastrically administrated 6 h after surgery and once daily for consecutive 15 days. Neurological function was assessed by the motor deficit score and beam walking test. T2 relaxation mapping and diffusion tensor imaging (DTI) were applied for detecting cerebral tissues damages and microstructural integrity of axons. Luxol fast blue (LFB) and transmission electron microscope (TEM) were performed to evaluate histopathology in myelinated axons. Double immunofluorescent staining was conducted to assess oligodendrogenesis. Furthermore, the protein expressions regarding to axonal remodeling related signaling pathways were detected by Western blot assays. RESULTS: TSTT treatment (65, 33 mg/kg) markedly improved motor function after ischemic stroke. T2 mapping MRI demonstrated that TSTT decreased lesion volumes, and DTI further confirmed that TSTT preserved axonal microstructure of the sensorimotor cortex and internal capsule. Meanwhile, diffusion tensor tractography (DTT) showed that TSTT elevated correspondent density and length of fiber in the internal capsule. These MRI measurements were confirmed by histological examinations. Notably, TSTT significantly increased Ki67/NG2, Ki67/CNPase double-labeled cells along the boundary zone of ischemic cortex and striatum. Meanwhile, TSTT treatment up-regulated the phosphorylation level of Ser 9 in GSK-3ß, and down-regulated phosphorylated ß-catenin and CRMP-2 expression. CONCLUSION: Taken together, our findings indicated that TSTT (65, 33 mg/kg) enhanced post-stroke functional recovery, amplified endogenous oligodendrogenesis and promoted axonal regeneration. The beneficial role of TSTT might be correlated with GSK-3/ß-catenin/CRMP-2 modulating axonal reorganization after ischemic stroke.

Dissipation of antibiotic resistance genes in manure-amended agricultural soil.

Soil antibiotic resistance due to animal manure application is of great concern in recent years. Little is known about the fate of antibiotic resistance genes (ARGs) in agricultural soils associated with long-term manure application. Here we used soil microcosms to investigate the dissipation of ARGs and the change of bacterial community in agricultural soil originated from a vegetable field which had received 24 years' swine manure application. Soil microcosms were conducted at different soil moistures and with or without biochar over a testing period of two years in lab. Results showed that continuous manure application induced an accumulation of ARGs in soil, wherein the dissipation of ARGs differed from those in non-manure amended soil. ARGs persisted in soils at least two years, although their abundance declined gradually. Meanwhile, soil moisture and biochar had significant impact on the fate of ARGs. ARGs dissipated faster in soil with higher moisture. Biochar amendment contributed to the maintenance of bacterial diversity. Within the two years of simulation experiment, biochar enhanced soil ARG retention as they dissipated slowly in the soil amended with biochar. Succession of microbial community may have sustained the transfer and resilience of ARGs. This study provides insight into the dissipation of antibiotic resistance genes in manure-applied agricultural soil.