Comparative genomics and phylogenomics of the genus Glycyrrhiza (Fabaceae) based on chloroplast genomes.

Glycyrrhiza (Fabaceae) species are rich in metabolites and widely used in medicine. Research on the chloroplast genome of Glycyrrhiza is important for understanding its phylogenetics, biogeography, genetic diversity, species identification, and medicinal properties. In this study, comparative genomics and phylogenomics of Glycyrrhiza were analyzed based on the chloroplast genome. The chloroplast genomes of six Glycyrrhiza species were obtained using various assembly and annotation tools. The final assembled chloroplast genome sizes for the six Glycyrrhiza species ranged from 126,380 bp to 129,115 bp, with a total of 109-110 genes annotated. Comparative genomics results showed that the chloroplast genomes of Glycyrrhiza showed typically lacking inverted repeat regions, and the genome length, structure, GC content, codon usage, and gene distribution were highly similar. Bioinformatics analysis revealed the presence of 69-96 simple sequence repeats and 61-138 long repeats in the chloroplast genomes. Combining the results of mVISTA and nucleotide diversity, four highly variable regions were screened for species identification and relationship studies. Selection pressure analysis indicated overall purifying selection in the chloroplast genomes of Glycyrrhiza, with a few positively selected genes potentially linked to environmental adaptation. Phylogenetic analyses involving all tribes of Fabaceae with published chloroplast genomes elucidated the evolutionary relationships, and divergence time estimation estimated the chronological order of species differentiations within the Fabaceae family. The results of phylogenetic analysis indicated that species from the six subfamilies formed distinct clusters, consistent with the classification scheme of the six subfamilies. In addition, the inverted repeat-lacking clade in the subfamily Papilionoideae clustered together, and it was the last to differentiate. Co-linear analysis confirmed the conserved nature of Glycyrrhiza chloroplast genomes, and instances of gene rearrangements and inversions were observed in the subfamily Papilionoideae.

Single-cell RNA sequencing analysis to evaluate antimony exposure effects on cell-lineage communications within the Drosophila testicular niche.

The increasing production and prevalence of antimony (Sb)-related products raise concerns regarding its potential hazards to reproductive health. Upon environmental exposure, Sb reportedly induces testicular toxicity during spermatogenesis; moreover, it is known to affect various testicular cell populations, particularly germline stem cell populations. However, the cell-cell communication resulting from Sb exposure within the testicular niche remains poorly understood. To address this gap, herein we analyzed testicular single-cell RNA sequencing data from Sb-exposed Drosophila. Our findings revealed that the epidermal growth factor receptor (EGFR) and WNT signaling pathways were associated with the stem cell niche in Drosophila testes, which may disrupt the homeostasis of the testicular niche in Drosophila. Furthermore, we identified several ligand-receptor pairs, facilitating the elucidation of intercellular crosstalk involved in Sb-mediated reproductive toxicology. We employed scRNA-seq analysis and conducted functional verification to investigate the expression patterns of core downstream factors associated with EGFR and WNT signatures in the testes under the influence of Sb exposure. Altogether, our results shed light on the potential mechanisms of Sb exposure-mediated testicular cell-lineage communications.

Protective effects of curcumin on desipramine-induced islet ß-cell damage via AKAP150/PKA/PP2B complex.

Tricyclic antidepressants (TCAs) are widely used to treat depression and anxiety-related mood disorders. But evidence shows that TCAs elevate blood glucose levels and inhibit insulin secretion, suggesting that TCAs are a risk factor, particularly for individuals with diabetes. Curcumin is a bioactive molecule from the rhizome of the Curcuma longa plant, which has shown both antidepressant and anti-diabetic activities. In the present study, we investigated the protective effect of curcumin against desipramine-induced apoptosis in ß cells and the underlying molecular mechanisms. In the mouse forced swimming test (FST), we found that lower doses of desipramine (5 and 10 mg/kg) or curcumin (2.5 mg/kg) alone did not affect the immobility time, whereas combined treatment with curcumin (2.5 mg/kg) and desipramine (5, 10 mg/kg) significantly decreased the immobility time. Furthermore, desipramine dose-dependently inhibited insulin secretion and elevated blood glucose levels, whereas the combined treatment normalized insulin secretion and blood glucose levels. In RIN-m5F pancreatic ß-cells, desipramine (10 µM) significantly reduced the cell viability, whereas desipramine combined with curcumin dose-dependently prevented the desipramine-induced impairment in glucose-induced insulin release, most effectively with curcumin (1 and 10 µM). We demonstrated that desipramine treatment promoted the cleavage and activation of Caspase 3 in RIN-m5F cells. Curcumin treatment inhibited desipramine-induced apoptosis, increased mitochondrial membrane potential and Bcl-2/Bax ratio. Desipramine increased the generation of reactive oxygen species, which was reversed by curcumin treatment. Curcumin also inhibited the translocation of forkhead box protein O1 (FOXO1) from the cytoplasm to the nucleus and suppressed the binding of A-kinase anchor protein 150 (AKAP150) to protein phosphatase 2B (PP2B, known as calcineurin) that was induced by desipramine. These results suggest that curcumin protects RIN-m5F pancreatic ß-cells against desipramine-induced apoptosis by inhibiting the phosphoinositide 3-kinase/AKT/FOXO1 pathway and the AKAP150/PKA/PP2B interaction. This study suggests that curcumin may have therapeutic potential as an adjunct to antidepressant treatment.

Extracellular fibrin promotes non-small cell lung cancer progression through integrin ß1/PTEN/AKT signaling.

The extracellular matrix (ECM) has been strongly correlated with cancer progression in various tumor types. However, the specific mechanisms underlying ECM-associated tumor behaviors remain unclear. In this study, we found an enriched distribution of fibrin in tumor tissues obtained from high-grade non-small cell lung cancer (NSCLC) patients. For further investigation, we established an in vitro 3D culture system using fibrin gel and found that NSCLC cells grown in this system exhibited increased stemness and tumorigenesis. Mechanistically, we demonstrated that fibrin facilitated the activation of the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway through integrin ß1. Furthermore, we found that blocking integrin ß1 signals enhanced the tumor suppressive effects of chemotherapy, providing a novel approach for clinical therapy for NSCLC.

Scutellaria baicalensis Georgi and Their Natural Flavonoid Compounds in the Treatment of Ovarian Cancer: A Review.

Ovarian cancer (OC) is one of the most common types of cancer in women with a high mortality rate, and the treatment of OC is prone to high recurrence rates and side effects. Scutellaria baicalensis (SB) is a herbal medicine with good anti-cancer activity, and several studies have shown that SB and its flavonoids have some anti-OC properties. This paper elucidated the common pathogenesis of OC, including cell proliferation and cell cycle regulation, cell invasion and metastasis, apoptosis and autophagy, drug resistance and angiogenesis. The mechanisms of SB and its flavonoids, wogonin, baicalein, baicalin, Oroxylin A, and scutellarein, in the treatment of OC, are revealed, such as wogonin inhibits proliferation, induces apoptosis, inhibits invasion and metastasis, and increases the cytotoxicity of the drug. Baicalein also inhibits vascular endothelial growth factor (VEGF) expression etc. Analyzing their advantages and disadvantages in treating OC provides a new perspective on the role of SB and its flavonoids in OC treatment. It serves as a resource for future OC research and development.

Mobile Robotic Balance Assistant (MRBA): a gait assistive and fall intervention robot for daily living.

BACKGROUND: Aging degrades the balance and locomotion ability due to frailty and pathological conditions. This demands balance rehabilitation and assistive technologies that help the affected population to regain mobility, independence, and improve their quality of life. While many overground gait rehabilitation and assistive robots exist in the market, none are designed to be used at home or in community settings. METHODS: A device named Mobile Robotic Balance Assistant (MRBA) is developed to address this problem. MRBA is a hybrid of a gait assistive robot and a powered wheelchair. When the user is walking around performing activities of daily living, the robot follows the person and provides support at the pelvic area in case of loss of balance. It can also be transformed into a wheelchair if the user wants to sit down or commute. To achieve instability detection, sensory data from the robot are compared with a predefined threshold; a fall is identified if the value exceeds the threshold. The experiments involve both healthy young subjects and an individual with spinal cord injury (SCI). Spatial Parametric Mapping is used to assess the effect of the robot on lower limb joint kinematics during walking. The instability detection algorithm is evaluated by calculating the sensitivity and specificity in identifying normal walking and simulated falls. RESULTS: When walking with MRBA, the healthy subjects have a lower speed, smaller step length and longer step time. The SCI subject experiences similar changes as well as a decrease in step width that indicates better stability. Both groups of subjects have reduced joint range of motion. By comparing the force sensor measurement with a calibrated threshold, the instability detection algorithm can identify more than 93% of self-induced falls with a false alarm rate of 0%. CONCLUSIONS: While there is still room for improvement in the robot compliance and the instability identification, the study demonstrates the first step in bringing gait assistive technologies into homes. We hope that the robot can encourage the balance-impaired population to engage in more activities of daily living to improve their quality of life. Future research includes recruiting more subjects with balance difficulty to further refine the device functionalities.

GelMA-MXene hydrogel nerve conduits with microgrooves for spinal cord injury repair.

Repair of spinal cord injury (SCI) depends on microenvironment improvement and the reconnection between injured axons and regenerated neurons. Here, we fabricate a GelMA-MXene hydrogel nerve conduit with electrical conductivity and internal-facing longitudinal grooves and explore its function in SCI repair. It is found that the resultant grooved GelMA-MXene hydrogel could effectively promote the neural stem cells (NSCs) adhesion, directed proliferation and differentiation in vitro. Additionally, when the GelMA-MXene conduit loaded with NSCs (GMN) is implanted into the injured spinal cord site, effective repair capability for the complete transection of SCI was demonstrated. The GMN group shows remarkable nerve recovery and significantly higher BBB scores in comparison to the other groups. Therefore, GMN with the microgroove structure and loaded with NSCs is a promising strategy in treating SCI.

Conductive Nerve Guidance Conduits Based on Morpho Butterfly Wings for Peripheral Nerve Repair.

Peripheral nerve injury (PNI), causing loss of sensory and motor function, is a complex and challenging disease in the clinic due to the restricted regeneration capacity. Nerve guidance conduits (NGCs) have become a promising substitute for peripheral nerve regeneration, but their efficacy is often limited. Here, inspired by the physiological structures of peripheral nerves, we present a conductive topological scaffold for nerve repair by modifying Morpho butterfly wing with reduced graphene oxide (rGO) nanosheets and methacrylated gelatin (GelMA) hydrogel encapsulated brain-derived neurotrophic factor (BDNF). Benefiting from the biocompatibility of GelMA hydrogel, the conductivity of rGO and parallel nanoridge structures of wing scales, PC12 cells, and neural stem cells grown on the modified wing have an increased neurite length with guided cellular orientation. In addition, the NGCs are successfully obtained by manually rolling up the scaffolds and exhibited great performance in repairing 10 mm sciatic nerve defects in rats, and we believe that the NGCs can be applied in reparing longer nerve defects in the future by further optimization. We also demonstrate the feasibility of electrically conductive NGCs based on the rGO/BDNF/GelMA-integrated Morpho butterfly wing as functional nerve regeneration conduits, which may have potential value for application in repairing peripheral nerve injuries.

Emodin prevents renal ischemia-reperfusion injury via suppression of CAMKII/DRP1-mediated mitochondrial fission.

Acute kidney injury (AKI) is a serious threat to human health. Clinically, ischemia-reperfusion (I/R) injury is considered one of the most common contributors to AKI. Emodin has been reported to alleviate I/R injury in the heart, brain, and small intestine in rats and mice through its anti-inflammatory effects. The present study investigated whether emodin improved AKI induced by I/R and elucidated the molecular mechanisms. We used a mouse model of renal I/R injury and human renal tubular epithelial cell model of hypoxia/reoxygenation (H/R) injury. Ischemia/reperfusion resulted in renal dysfunction. Pretreatment with emodin ameliorated renal injury in mice following I/R injury. Emodin reduced mitochondrial-mediated apoptosis, suppressed the overproduction of mitochondrial reactive oxygen species and accelerated the recovery of adenosine triphosphate both in vivo and in vitro. Emodin prevented mitochondrial fission and restored the balance of mitochondrial dynamics. The phosphorylation of dynamin-related protein 1 (DRP1) at Ser616, a master regulator of mitochondrial fission, was upregulated in both models of I/R and H/R injury, and this upregulation was blocked by emodin. Using computational cognate protein kinase prediction and specific kinase inhibitors, we found that emodin inhibited the phosphorylation of calcium/calmodulin-dependent protein kinase II (https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1554), thereby inhibiting its kinase activity and reducing the phosphorylation of DRP1 at Ser616. The results demonstrated that emodin pretreatment could protect renal function by improving mitochondrial dysfunction induced by I/R.

A novel risk score predicts prognosis in melanoma: The combination of three tumor-infiltrating immune cells and four immune-related genes.

Tumor-infiltrating immune cells (TIICs) and immune-related genes (IRGs) of melanoma are associated with prognosis. However, whether the combination of TIICs and IRGs can be used as prognostic clinical biomarkers are still unknown. Here, we downloaded transcription profile of melanoma from TCGA. Then, three TIICs and four IRGs that associated with the overall survival were used to constructed the Immune Cell Score (ICS) and Immune Gene Score (IGS) respectively. Next, to improve the accuracy of ICS and IGS for melanoma prognostic, we combined the ICS and IGS constructed the Immune Cell and Gene Score (ICGS) model. ICGS had higher accuracy and predictive ability than ICS or IGS. Meanwhile, ICGS model reliability was validated by two independent datasets of melanoma. Functional enrichment and protein-protein interaction network analysis based on ICGS were performed to identify T cell mediated immune and inflammatory response are highly associated with melanoma.

Baicalin Inhibits Ferroptosis in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. To date, the exact etiology of ICH-induced brain injury is still unclear. Moreover, there is no effective treatment to delay or prevent disease progression currently. Increasing evidence suggests that ferroptosis plays a dominant role in the pathogenesis of ICH injury. Baicalin is a main active ingredient of Chinese herbal medicine Scutellaria baicalensis. It has been reported to exhibit neuroprotective effects against ICH-induced brain injury as well as reduce iron deposition in multiple tissues. Therefore, in this study, we focused on the protective mechanisms of baicalin against ferroptosis caused by ICH using a hemin-induced in vitro model and a Type IV collagenase-induced in vivo model. Our results revealed that baicalin enhanced cell viability and suppressed ferroptosis in rat pheochromocytoma PC12 cells treated with hemin, erastin and RSL3. Importantly, baicalin showed anti-ferroptosis effect on primary cortical neurons (PCN). Furthermore, baicalin alleviated motor deficits and brain injury in ICH model mice through inhibiting ferroptosis. Additionally, baicalin existed no obvious toxicity towards the liver and kidney of mice. Evidently, ferroptosis is a key pathological feature of ICH and baicalin can prevent the development of ferroptosis in ICH. As such, baicalin is a potential therapeutic drug for ICH treatment.

Nanoparticles improved resveratrol brain delivery and its therapeutic efficacy against intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a neurological disorder resulting from the nontraumatic rupture of blood vessels in the brain. Ferroptosis is a newly identified form of programmed cell death, which is an important pathological feature of ICH injury. At present, the therapeutic efficacy of ICH treatment is far from satisfactory, so it is urgent to develop a safer and more effective method to treat ICH injury. Resveratrol (Res), a widely used nonflavonoid polyphenol compound, plays a neuroprotective role in many diseases. However, its poor oral bioavailability limits its clinical application in ICH. Polymer nanoparticles (NPs) are a commonly used drug delivery matrix material with good biocompatibility. To improve its bioavailability and accumulation in the brain, we used NPs to encapsulate Res. These spherical Res nanoparticles (Res-NPs) had a particle size of 297.57 ± 7.07 nm, a PDI of 0.23 ± 0.02 and a zeta potential of -5.45 ± 0.27 mV. They could be taken up by Madin-Darby canine kidney (MDCK) cells through a variety of nonspecific endocytosis mechanisms, mainly mediated by clathrin and plasma membrane microcapsules. After entering the cell, Res-NPs tend to accumulate in the endoplasmic reticulum and lysosomes. In a zebrafish model, we observed that Res-NPs could transport across physiological barriers. In a Sprague-Dawley (SD) rat model, we found that Res-NPs had more desirable improvements in Res accumulation within the plasma and brain. Moreover, we demonstrated that Res-NPs were able to inhibit ferroptosis induced by erastin in HT22 mouse hippocampal cells, which are commonly used in in vitro studies to examine neuronal differentiation and neurotoxicity implicated in brain injuries or neurological diseases. Finally, in an ICH mouse model, we confirmed that Res-NPs are a safer and effective treatment for ICH injury. Collectively, Res-NPs are effective to improve Res brain delivery and its therapeutic efficacy in ICH treatment.

Electricity production and the analysis of the anode microbial community in a constructed wetland-microbial fuel cell.

The objective of this study is to assess bioelectricity generation, pollutant removal (COD, ammonium, nitrate) and the bacterial communities on anodes in constructed wetlands coupled with microbial fuel cells (CW-MFCs), through feeding the systems with three different types of synthetic wastewater (system 1: normal wastewater; system 2: ammonium-free wastewater; system 3: nitrate-free wastewater). Three CW-MFCs were operated with different wastewater concentrations and hydraulic retention times (HRTs) over a long time period (6 months). The results indicate that the maximum open circuit voltage (775.63 mV) and maximum power density (0.628 W m-3) were observed in system 3 (period 3), and that bioenergy production was inhibited in system 2, when feeding with ammonium-free wastewater continuously. COD removal rates in the three systems were similar during each period and ranged from 82.2 ± 6.8% to 98.3 ± 2.2%. Ammonium removal occurred at the air cathode of the CW-MFCs through nitrification, and a higher level of ammonium removal was found in system 1 (period 3) compared with the others. Meanwhile, denitrification occurred at the anaerobic anode of the CW-MFCs, and a large amount of nitrate was removed effectively. The highest nitrate removal rate was 98.8 ± 0.5% in system 2 (period 3). Additionally, four genera related to electricity generation were detected at the anode: Geothrix; Desulfovibrio; Desulfobulbus; and Geobacter. The relative abundances of Desulfovibrio, Desulfobulbus and Geothrix gradually increased during the three periods in system 3, which might be beneficial for bioelectricity generation. Further investigations are needed to optimize the CW-MFC performance and explain the mechanism behind the pollutant degradation and electron motion in the CW-MFCs.

Gold nanoclusters confined in a supercage of Y zeolite for aerobic oxidation of HMF under mild conditions.

Au nanoclusters with an average size of approximately 1 nm size supported on HY zeolite exhibit a superior catalytic performance for the selective oxidation of 5-hydroxymethyl-2-furfural (HMF) into 2,5-furandicarboxylic acid (FDCA). It achieved >99 % yield of 2,5-furandicarboxylic acid in water under mild conditions (60 °C, 0.3 MPa oxygen), which is much higher than that of Au supported on metal oxides/hydroxide (TiO2 , CeO2 , and Mg(OH)2 ) and channel-type zeolites (ZSM-5 and H-MOR). Detailed characterizations, such as X-ray diffraction, transmission electron microscopy, N2 -physisorption, and H2 -temperature-programmed reduction (TPR), revealed that the Au nanoclusters are well encapsulated in the HY zeolite supercage, which is considered to restrict and avoid further growing of the Au nanoclusters into large particles. The acidic hydroxyl groups of the supercage were proven to be responsible for the formation and stabilization of the gold nanoclusters. Moreover, the interaction between the hydroxyl groups in the supercage and the Au nanoclusters leads to electronic modification of the Au nanoparticles, which is supposed to contribute to the high efficiency in the catalytic oxidation of HMF to FDCA.

Gold nanoparticles confined in the interconnected carbon foams with high temperature stability.

Gold nanoparticle-carbon foam composites with highly-dispersed gold nanoparticles confined in the cavities were prepared. The gold nanoparticles are effectively separated from each other by permeable carbon shells, which show high temperature stability and were fully accessible to the substrate.

Facile preparation of highly-dispersed cobalt-silicon mixed oxide nanosphere and its catalytic application in cyclohexane selective oxidation.

Highly dispersed cobalt-silicon mixed oxide [Co-SiO2] nanosphere was successfully prepared with a modified reverse-phase microemulsion method. This material was characterized in detail by X-ray diffraction, transmission electron microscopy, Fourier transform infrared, ultraviolet-visible diffuse reflectance spectra, X-ray absorption spectroscopy near-edge structure, and N2 adsorption-desorption measurements. High valence state cobalt could be easily obtained without calcination, which is fascinating for the catalytic application for its strong oxidation ability. In the selective oxidation of cyclohexane, Co-SiO2 acted as an efficient catalyst, and good activity could be obtained under mild conditions.

The nature of surface oxides on corrosion-resistant nickel alloy covered by alkaline water.

A nickel alloy with high chrome and molybdenum content was found to form a highly resistive and passive oxide layer. The donor density and mobility of ions in the oxide layer has been determined as a function of the electrical potential when alkaline water layers are on the alloy surface in order to account for the relative inertness of the nickel alloy in corrosive environments.

Flexible Thick-Film Electrochemical Sensors: Impact of Mechanical Bending and Stress on the Electrochemical Behavior.

The influence of the mechanical bending, rolling and crimping of flexible screen-printed electrodes upon their electrical properties and electrochemical behavior has been elucidated. Three different flexible plastic substrates, Mylar, polyethylene naphthalate (PEN), and Kapton, have been tested in connection to the printing of graphite ink working electrodes. Our data indicate that flexible printed electrodes can be bent to extremely small radii of curvature and still function well, despite a marginal increase the electrical resistance. Below critical radii of curvature of ~8 mm, full recovery of the electrical resistance occurs upon strain release. The electrochemical response is maintained for sub-mm bending radii and a 180° pinch of the electrode does not lead to device failure. The electrodes appear to be resistant to repeated bending. Such capabilities are demonstrated using model compounds, including ferrocyanide, trinitrotoluene (TNT) and nitronaphthalene (NN). These printed electrodes hold great promise for widespread applications requiring flexible, yet robust non-planar sensing devices.