Low-Toxicity Self-Photosensitized Biohybrid Systems for Enhanced Light-Driven H2 Production.

Nanoparticles (NPs) represent a potential optoelectronic source capable of significantly boosting hydrogen production; however, their inevitable cytotoxicity may lead to oxidative damage of bacterial cell membranes. In this study, we employed non-photosynthetic Escherichia coli K-12 as a model organism and utilized self-assembled cadmium sulfide (CdS) nanoparticles to construct a low-toxicity and hydrogen-production-enhancing self-photosensitive hybrid system. To mitigate the cytotoxicity of CdS NPs and synthesize biocompatible CdS NPs on the cell surface, we employed engineered E. coli (efeB/OE) for bioremediation, achieving this goal through the overexpression of the peroxidase enzyme (EfeB). A comparative analysis with E. coli-CdS revealed a significant downregulation of genes encoding oxidative stress proteins in efeB/OE-CdS post-irradiation. Atomic force microscopy (AFM) confirmed the stability of bacterial cell membranes. Due to the enhanced stability of the cell membrane, the hydrogen yield of the efeB/OE-CdS system increased by 1.3 times compared to the control, accompanied by a 49.1% reduction in malondialdehyde (MDA) content. This study proposes an effective strategy to alleviate the toxicity of mixed biological nanoparticle systems and efficiently harness optoelectronic electrons, thereby achieving higher hydrogen production in bioremediation.

The effect of Par3 on the cellular junctions and biological functions of odontoblast-lineage cells.

Perfect intercellular junctions are key for odontoblast barrier function. However, whether Partitioning defective-3 (Par3) is expressed in odontoblasts and its potential effects on odontoblast junctions are unknown. Herein, we investigated the effect of Par3 on cellular junctions and the biological behavior of odontoblast-lineage cells (OLCs). Whole-transcriptome sequencing was used to analyze the effects of Par3 on OLCs and the underlying molecular mechanism. Par3 was detected under physiological and inflammatory conditions in OLCs. To investigate the regulatory effect of Par3 on junctions between mouse OLCs, the effects of Par3 downregulation on the proliferation, migration, cycle and apoptosis of OLCs were detected by 5-ethyl-2'-deoxyuridine (EdU) and Transwell assays and flow cytometry. Western blotting and alizarin red S and alkaline phosphatase (ALP) staining were used to observe the effect of Par3 downregulation on OLC mineralization. Whole-transcriptome sequencing was used to investigate the biological role of Par3 in OLCs and potential molecular mechanisms. Par3 was located along the odontoblast layer in the rat pulp tissue and in the cytoplasm of OLCs. Par3 expression was downregulated under inflammatory conditions. The OLC junctions were discontinuous, and total Zona occluden-1 (ZO-1) expression and expression of ZO-1 at the membrane in OLCs were reduced after Par3 silencing (P < 0.05). Expression of a junction-related protein (ZO-1) was downregulated after the downregulation of Par3 (P < 0.05), and ZO-1 moved from the cell membrane to the cytoplasm. OLC proliferation and migration were enhanced, but apoptosis and mineralization were inhibited in shPar3-transfected cells (P < 0.05). Sequencing identified 2996 differentially expressed genes (DEGs), which were mainly enriched in the response to stimuli and binding. Downregulation of Par3 could overactivate the PI3k-AKT pathway by promoting AKT phosphorylation (P < 0.05). Downregulation of Par3 may disrupt junctions between OLCs by affecting ZO-1 expression and distribution and promote OLC proliferation and migration but inhibit OLC mineralization. Par3 may interact with 14-3-3 proteins for PI3K-AKT pathway activation to affect OLC junctions and function.

Fe3 O4 nanozyme coating enhances light-driven biohydrogen production in self-photosensitized Shewanella oneidensis-CdS hybrid systems.

Solar-driven biohybrid systems that produce chemical energy are a valuable objective in ongoing research. However, reactive oxygen species (ROS) that accompany nanoparticle production under light radiation severely affect the efficiency of biohybrid systems. In this study, we successfully constructed a two-hybrid system, Shewanella oneidensis-CdS and S. oneidensis-CdS@Fe3 O4 , in a simple, economical, and gentle manner. With the Fe3 O4 coating, ROS were considerably eliminated; the hydroxyl radical, superoxide radical, and hydrogen peroxide contents were reduced by 66.7%, 65.4%, and 72%, respectively, during light-driven S. oneidensis-CdS hydrogen production. S. oneidensis-CdS@Fe3 O4 showed a 2.6-fold higher hydrogen production (70 h) than S. oneidensis-CdS. Moreover, the S. oneidensis-CdS system produced an additional 367.8 µmol g-dcw-1 (70 h) of hydrogen compared with S. oneidensis during irradiation. The apparent quantum efficiencies of S. oneidensis-CdS and S. oneidensis-CdS@Fe3 O4 were 6.2% and 11.5%, respectively, exceeding values previously reported. In conclusion, a stable nanozyme coating effectively inhibited the cytotoxicity of CdS nanoparticles, providing an excellent production environment for bacteria. This study provides a rational strategy for protecting biohybrid systems from ROS toxicity and contributes to more efficient solar energy conversion in the future.

Spatial and Temporal Trends in Travel for COVID-19 Vaccinations.

Introduction: Understanding spatial and temporal trends in travel for COVID-19 vaccinations by key demographic characteristics (i.e., gender, race, age) is important for ensuring equitable access to and increasing distribution efficiency of vaccines and other health services. The aim of this study is to examine trends in travel distance for COVID-19 vaccinations over the course of the vaccination rollout in North Carolina. Methods: Data were collected using electronic medical records of individuals who had first- or single-dose COVID-19 vaccination appointments through UNC Health between December 15, 2020, and August 31, 2021 (N = 204,718). Travel distances to appointments were calculated using the Euclidean distance from individuals' home ZIP code centroids to clinic addresses. Descriptive statistics and multivariable regression models with individuals' home ZIP codes incorporated as fixed effects were used to examine differences in travel distances by gender, race, and age. Results: Males and White individuals traveled significantly farther for vaccination appointments throughout the vaccination rollout. On average, females traveled 14. 4 miles, 3.5% shorter distances than males; Black individuals traveled 13.6 miles, 10.0% shorter distances than White individuals; and people aged 65 and older traveled 14.5 miles, 2.6% longer distances than younger people living in the same ZIP code. Conclusions: Controlling for socioeconomic status and spatial proximity to vaccination clinics at the ZIP code level, males and White individuals traveled longer distances for vaccination appointments, demonstrating more ability to travel for vaccinations. Results indicate a need to consider differential ability to travel to vaccinations by key demographic characteristics in COVID-19 vaccination programs and future mass health service delivery efforts.

Fo-Shou-San Ameliorates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment in Mice by Regulating NRF2/HO-1 Pathway Against Ferroptosis.

BACKGROUND: Fo-Shou-San (FSS) is a traditional Chinese medicine (TCM) decoction that can effectively treat vascular dementia (VD). In the face of unclear pharmacological mechanisms, we set out to validate that FSS treats chronic cerebral hypoperfusion (CCH)-induced cognitive impairment in mice. METHODS: CCH animal model caused by permanent right unilateral common carotid arteries occlusion (rUCCAO) was established to verify that FSS could treat subcortical ischemic vascular dementia (SIVD). We performed novel object recognition test and Morris water maze test, observed morphological changes via HE and Nissl staining, and detected hippocampus apoptosis by TUNEL staining and oxidative stress by biochemical assays. Ferroptosis-related markers and NRF2/HO-1 signaling-related expressions were examined via qPCR and immunofluorescence staining. RESULTS: We found that FSS ameliorated cognitive disorders, and lessened oxidative stress by decreasing MDA and GSH-PX while increasing the reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) ratio, which are associated with ferroptosis. Additionally, FSS reduced expression of SLC7A11, GPX4, ROX and 4HNE, as vital markers of ferroptosis. Further, FSS regulated NRF2/HO-1 signaling by downregulating NRF2 and HO-1. CONCLUSIONS: Our study suggests that FSS may ameliorate chronic cerebral hypoperfusion-induced cognitive deficits through regulation of the NRF2/HO-1 pathway against ferroptosis. Taken together, our study highlights the neuroprotective efficacy of FSS.

Cobalt-doped double-layer α-Fe2O3 nanorod arrays for enhanced photoelectrochemical reduction of Cr(VI).

Element doping is an important method for improving the performance levels of photoelectrochemical (PEC) cells. Nevertheless, to date, the PEC conversion efficiency and photocurrent characteristics of the available photoanodes remain very low. In this study, cobalt (Co) was selectively doped into the bottom and/or top layers of double-layered α-Fe2O3 nanorod arrays grown on conductive transparent substrates (F:SnO2, FTO) via a two-step hydrothermal method; this process was performed to enhance the charge transfer ability and thus significantly improve the PEC performance. The light response capabilities of all α-Fe2O3 films were evaluated by an electrochemical workstation under dark or visible light irradiation conditions. The sample of Co doped in the bottom layer exhibited a high photoelectrochemical performance, achieving a current density of 1.37 mA/cm2 at + 1.0 V versus saturated calomel electrode (SCE); additionally, the sample exhibited a photoelectric synergistic ability to reduce Cr(VI) in an aqueous solution, with 84.85% reduction in 180 min. Under the influence of the electric field inside the double-layer electrode, the photoexcited electrons and holes are transferred to the surfaces of the FTO substrate and the photoanode, increasing the current density and enhancing Cr(VI) reduction. The results of this study offer an alternative approach for designing novel photoanodes with improved PEC performance levels by engineering the electron density distribution and band structure for efficient carrier separation; the results may provide new solutions in heavy metal reduction and contaminant degradation projects.

Light-driven biodegradation of azo dyes by Shewanella decolorationis-CdS biohybrid in wastewater lacking electron donors.

The lack of electron donors prevents the effective degradation of azo dyes by bacteria, which severely limits the practical application of conventional biological treatment. Herein, we innovatively designed a bio-photoelectric reduction degradation system composed of CdS and Shewanella decolorationis, which could effectively degrade amaranth in anaerobic conditions driven by light when electron donors were unavailable. Compared with bare S. decolorationis and S. decolorationis (heat-killed)-CdS biohybrid, S. decolorationis-CdS biohybrid had 39.36-fold and 3.82-fold higher first-order kinetic constants, respectively. The morphology, particle size, elemental composition, crystalline type, photovoltaic properties, and band structure of the nanoparticles synthesized by S. decolorationis were carefully examined and analyzed. Light-driven biodegradation experiments showed that amaranth was degraded by the synergy of CdS and S. decolorationis. Reductive degradation of amaranth by electrons was demonstrated by electron and hole trapping. The effect of potential coexisting contaminants, which might serve as hole scavengers, on the degradation of amaranth was evaluated. Membrane protein inhibition experiments also suggested that NADH dehydrogenase, menaquinone, and cytochrome P450 played an important role in electron transfer between CdS and Shewanella decolorationis. The cyclic conversion of NAD+/NADH was probably the most critical rate-limiting step. Electrochemical measurements suggested that faster electron transfer might facilitate the degradation of amaranth. Our findings might contribute to the degradation of azo dyes in wastewater lacking electron donors and deepen our recognition of the microbe-material interface. KEY POINTS: • A BPRDS was constructed with Shewanella decolorationis and CdS. • Amaranth was effectively degraded by BPRDS in anaerobic conditions driven by light. • NDH, MQ, and CYP450 were involved in electron transfer.

Transportation barriers to care among frequent health care users during the COVID pandemic.

BACKGROUND: Transportation problems are known barriers to health care and can result in late arrivals and delayed or missed care. Groups already prone to greater social and economic disadvantage, including low-income individuals and people with chronic conditions, encounter more transportation barriers and experience greater negative health care consequences. Addressing transportation barriers is important not only for mitigating adverse health care outcomes among patients, but also for avoiding additional costs to the health care system. In this study, we investigate transportation barriers to accessing health care services during the COVID-19 pandemic among high-frequency health care users. METHODS: A web-based survey was administered to North Carolina residents aged 18 and older in the UNC Health system who were enrolled in Medicaid or Medicare and had at least six outpatient medical appointments in the past year. 323 complete responses were analyzed to investigate the prevalence of reporting transportation barriers that resulted in having arrived late to, delayed, or missed care, as well as relationships between demographic and other independent variables and transportation barriers. Qualitative analyses were performed on text response data to explain transportation barriers. RESULTS: Approximately 1 in 3 respondents experienced transportation barriers to health care between June 2020 and June 2021. Multivariate logistic regressions indicate individuals aged 18-64, people with disabilities, and people without a household vehicle were significantly more likely to encounter transportation barriers. Costs of traveling for medical appointments and a lack of driver or car availability emerged as major transportation barriers; however, respondents explained that barriers were often complex, involving circumstantial problems related to one's ability to access and pay for transportation as well as to personal health. CONCLUSIONS: To address transportation barriers, we recommend more coordination between transportation and health professionals and the implementation of programs that expand access to and improve patient awareness of health care mobility services. We also recommend transportation and health entities direct resources to address transportation barriers equitably, as barriers disproportionately burden younger adults under age 65 enrolled in public insurance programs.

Photocatalytic performance of an α-Fe2O3 electrode and its effects on the growth and metabolism of Citrobacter freundii.

Electronic exchanges occur between semiconductor minerals and microorganisms. However, researchers have focused on the photocatalytic degradation of pollutants by semiconductor minerals, and there is a limited amount of studies on semiconductor photogenerated electrons that influence the growth and energetic mechanisms of bacteria. Bioelectrochemical systems (BES) are important new bioengineering technologies for investigating the mechanisms by which bacteria absorb electrons. In this work, we built a BES that used α-Fe2O3 nanorods as a photoanode and Citrobacter freundii as bio-cathode bacteria to explore the effect of photoelectrons on C. freundii growth and metabolism. The photoanode was prepared by a hydrothermal synthesis method. As confirmed by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), the photoanode was made of α-Fe2O3. Corresponding scanning electron microscope (SEM) images showed that α-Fe2O3 nanorod arrays formed with a diameter of 50 nm, and the band gap was 2.03 eV, as indicated by UV-vis diffuse reflectance spectroscopy (UV-vis DRS). The C. freundii growth metabolism changed significantly because of photoelectrons; under light conditions, the growth rate of C. freundii significantly accelerated, and as inferred from the three-dimensional fluorescence spectrum, the protein, humic acid, and NADH concentrations were significantly higher at 72 h. According to the changes in the organic acid content, photoelectrons participated in the reductive tricarboxylic acid cycle (rTCA) to enhance growth and metabolism. The results of the study have broad implications for advancing fields that study the effects of semiconductor minerals on electroactive microorganisms and the semiconductor-photoelectronic transport mechanisms of electroautotrophic microorganisms. KEY POINTS: • For the first time, A BES was built that used α-Fe2O3 nanorods as a photoanode and C. freundii as a bio-cathode bacteria. • Photoelectrons produced by α-Fe2O3 photoelectrode promote the growth of C. freundii. • Effects of photoelectrons on C. freundii metabolism were conjectured by the changes of organic acids and NADH.

Socio-economic disparities in activity-travel behavior adaptation during the COVID-19 pandemic in North Carolina.

The COVID-19 pandemic significantly affected human mobility. This study examines the changes in people's activity-travel behavior over 23 months (from Jan 2020 to Nov 2021) and how these changes are associated with the socio-economic status (SES) at the block group level in North Carolina. We identified 5 pandemic stages with different restriction regimes: the pre-pandemic, lockdown, reopening stage, restriction, and complete opening stage. Using the block-group mobility data from SafeGraph, we quantify visits to 8 types of destinations during the 5 stages. We construct regression models with interaction terms between SES and stages and find that visit patterns during the pandemic vary for different types of destinations and SES areas. Specifically, we show that visits to retail stores have a slight decrease for low and medium SES areas, and visits to retail stores and restaurants and bars bounced back immediately after the lockdown for all SES areas. The results suggest that people in low SES areas continued traveling during the pandemic. Transportation planners and policymakers should carefully design the transportation system to satisfy travel needs of those residents. Furthermore, the results also highlight the importance of designing mitigation policies that recognize the immediate recovery of visits to retail locations, restaurants, and bars.

Label-free fluorescence detection of hydrogen peroxide and glucose based on the Ni-MOF nanozyme-induced self-ligand emission.

A bifunctional Ni-MOF nanosheet was synthesized and developed for label-free fluorescent detection of H2O2 and glucose. The Ni-MOF exhibited intrinsic peroxidase-like activity and its catalytic activity was demonstrated to be originated from the hydroxyl radicals (•OH) produced in catalytic process. Since the generated •OH enabled terephthalic acid, the non-fluorescent organic ligand of Ni-MOF, to form a strongly fluorescent 2-hydroxy terephthalic acid, the Ni-MOF nanozyme was endowed with dual-function properties of mimicking peroxidase and emitting fluorescence. Based on this bifunctional Ni-MOF nanozyme, the proposed label-free fluorescence sensing strategy was applied to detecting H2O2 and glucose with wide linear ranges of 0.1-20 mM and 8-30 µM, and low detection limits of 4.0 × 10-5 M and 4.0 × 10-6 M, respectively. Furthermore, the bifunctional Ni-MOF-based label-free sensing platform was successfully used for the glucose detection in human serum samples, showing good reproducibility and high accuracy. This strategy provides a green and sensitive method for the determination of small biomolecules in practical applications by the combination of enzyme cascade reaction.

Profiling long noncoding RNA alterations during the stromal cell-derived factor-1α-induced odontogenic differentiation of human dental pulp stem cells.

OBJECTIVE: The purpose of this study was to investigate the differential expression of long noncoding RNAs (lncRNAs) in dental pulp stem cells (DPSCs) after stromal cell-derived factor-1α (SDF-1α) induction and to explore the lncRNAs that regulate the odontogenic differentiation and migration of DPSCs. DESIGN: We examined the altered expression of lncRNAs in DPSCs after SDF-1α induction by performing lncRNA microarray and qRT-PCR analyses. Moreover, a bioinformatics analysis was conducted to predict the interactions of lncRNAs and identify core regulatory factors. A small interfering RNA (siRNA) was used to knock down lncRNA AC080037.1 expression in DPSCs. Cell transmigration assays, alizarin red staining, qRT-PCR and Western blotting were performed to detect the expression of osteo/dentinogenic differentiation markers or Rho GTPase after lncRNA knockdown in DPSCs. RESULTS: The microarray analysis identified 206 differentially expressed lncRNAs at 7 days after treatment. One lncRNA, AC080037.1, was shown to regulate the odontogenic differentiation of DPSCs. An siRNA targeting lncRNA AC080037.1 suppressed DPSCs migration and the expression of Rho GTPase induced by SDF-1α. Moreover, AC080037.1 knockdown significantly affected mineralized nodule formation and substantially suppressed runt-related factor-2 (RUNX-2), dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) expression in DPSCs. CONCLUSIONS: Our results revealed the differential expression of lncRNAs in DPSCs before and after SDF-1α induction. Furthermore, we highlighted the significant involvement of one lncRNA, AC080037.1, in the positive regulation of the osteo/odontogenic differentiation of DPSCs and indicated that this lncRNA might be a potential target in regenerative endodontics. These findings may further advance translational studies of pulp engineering.

Fabrication and characterization of CdS nanowires templated in tobacco mosaic virus with improved photocatalytic ability.

Using a virus as a template to synthesize nanomaterial is a simple, green, and controllable method to acquire unique structure nanoparticles. In this study, CdS nanowires were synthesized using the tobacco mosaic virus (TMV) as a template and for deposition in the inner center channel of TMV. TMV/CdS was successfully characterized, with the results showing a diameter of 4.0 nm, a cubic-phase composition, and strong fluorescence emission peaks, with an absorption edge of 566 nm and bandgap energy of 2.28 eV. The bandgap energy is narrower than that of template-free CdS. Furthermore, TMV/CdS exhibited an increased transient photocurrent, which was attributed to the effective separation of electron-hole pairs. The photoactivities of TMV/CdS and template-free CdS were tested; the results showed that the TMV/CdS had a better performance in methylene blue (MB) photodegradation, indicating that the photoactivity of TMV/CdS was higher than that of the template-free CdS. Further research on TMV/CdS regarding the photocatalytic mechanism showed that O2•- and •OH were the major species involved in photocatalysis, rather than holes (h+). Therefore, TMV/CdS might have applications as a novel visible-light-responsive photocatalyst. KEY POINTS: • CdS nanowires were firstly synthesized in the inner center channel of TMV • TMV/CdS presented higher photocatalytic efficiency compared with template-free CdS • The O2•- and •OH were responsible for the photocatalytic reaction of TMV/CdS.

Health care visits during the COVID-19 pandemic: A spatial and temporal analysis of mobile device data.

Transportation disruptions caused by COVID-19 have exacerbated difficulties in health care delivery and access, which may lead to changes in health care use. This study uses mobile device data from SafeGraph to explore the temporal patterns of visits to health care points of interest (POIs) during 2020 and examines how these patterns are associated with socio-demographic and spatial characteristics at the Census Block Group level in North Carolina. Specifically, using the K-medoid time-series clustering method, we identify three distinct types of temporal patterns of visits to health care facilities. Furthermore, by estimating multinomial logit models, we find that Census Block Groups with higher percentages of elderly persons, minorities, low-income individuals, and people without vehicle access are areas most at-risk for decreased health care access during the pandemic and exhibit lower health care access prior to the pandemic. The results suggest that the ability to conduct in-person medical visits during the pandemic has been unequally distributed, which highlights the importance of tailoring policy strategies for specific socio-demographic groups to ensure equitable health care access and delivery.

Mechanism of validamycin A inhibiting DON biosynthesis and synergizing with DMI fungicides against Fusarium graminearum.

Deoxynivalenol (DON) is a vital virulence factor of Fusarium graminearum, which causes Fusarium head blight (FHB). We recently found that validamycin A (VMA), an aminoglycoside antibiotic, can be used to control FHB and inhibit DON contamination, but its molecular mechanism is still unclear. In this study, we found that both neutral and acid trehalase (FgNTH and FgATH) are the targets of VMA in F. graminearum, and the deficiency of FgNTH and FgATH reduces the sensitivity to VMA by 2.12- and 1.79-fold, respectively, indicating that FgNTH is the main target of VMA. We found FgNTH is responsible for vegetative growth, FgATH is critical to sexual reproduction, and both of them play an important role in conidiation and virulence in F. graminearum. We found that FgNTH resided in the cytoplasm, affected the localization of FgATH, and positively regulated DON biosynthesis; however, FgATH resided in vacuole and negatively regulated DON biosynthesis. FgNTH interacted with FgPK (pyruvate kinase), a key enzyme in glycolysis, and the interaction was reduced by VMA; the deficiency of FgNTH affected the localization of FgPK under DON induction condition. Strains with a deficiency of FgNTH were more sensitive to demethylation inhibitor (DMI) fungicides. FgNTH regulated the expression level of FgCYP51A and FgCYP51B by interacting with FgCYP51B. Taken together, VMA inhibits DON biosynthesis by targeting FgNTH and reducing the interaction between FgNTH and FgPK, and synergizes with DMI fungicides against F. graminearum by decreasing FgCYP51A and FgCYP51B expression.

Validamycin A Induces Broad-Spectrum Resistance Involving Salicylic Acid and Jasmonic Acid/Ethylene Signaling Pathways.

Validamycin A (VMA) is an aminoglycoside antibiotic used to control rice sheath blight. Although it has been reported that VMA can induce the plant defense responses, the mechanism remains poorly understood. Here, we found that reactive oxygen species (ROS) bursts and callose deposition in Arabidopsis thaliana, rice (Oryza sativa L.), and wheat (Triticum aestivum L.) were induced by VMA and were most intense with 10 µg of VMA per milliliter at 24 h. Moreover, we showed that VMA induced resistance against Pseudomonas syringae, Botrytis cinerea, and Fusarium graminearum in Arabidopsis leaves, indicating that VMA induces broad-spectrum disease resistance in both dicots and monocots. In addition, VMA-mediated resistance against P. syringae was not induced in NahG transgenic plants, was partially decreased in npr1 mutants, and VMA-mediated resistance to B. cinerea was not induced in npr1, jar1, and ein2 mutants. These results strongly indicated that VMA triggers plant defense responses to both biotrophic and necrotrophic pathogens involved in salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) signaling pathways and is dependent on NPR1. In addition, transcriptome analysis further revealed that VMA regulated the expression of genes involved in SA, JA/ET, abscisic acid (ABA), and auxin signal pathways. Taken together, VMA induces systemic resistance involving in SA and JA/ET signaling pathways and also exerts a positive influence on ABA and auxin signaling pathways. Our study highlights the creative application of VMA in triggering plant defense responses against plant pathogens, providing a valuable insight into applying VMA to enhance plant resistance and reduce the use of chemical pesticides.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

A Defect in the Twin-Arginine Translocation Pathway Decreases the Tolerance of Xanthomonas campestris pv. campestris to Phenazines.

Phenazine-1-carboxylic acid (PCA), a member of phenazines secreted by microorganisms, inhibits the growth of many bacteria and fungi. Xanthomonas campestris pv. campestris is the causal agent of black rot, the most important disease of cruciferous crops worldwide, and is more tolerant to PCA than other Xanthomonas species. Previous studies reported that reactive oxygen species (ROS) scavenging ability is involved in regulating the PCA tolerance of Xanthomonas species. Additionally, the cytochrome c maturation (CCM) system has been found to play a more important role in tolerance to phenazines than the ROS scavenging system. In this study, a highly PCA-sensitive insertion mutant of X. campestris pv. campestris, X-5, was identified and studied. The insertion site of X-5 was found to be in tatB gene (XC_4183), which encodes a subunit of the twin-arginine translocation (TAT) complex. Disruption of the three genes of TAT pathway resulted in decreased biological fitness and reduced tolerance to phenazines in comparison with the wild-type strain 8004. These results imply that the tolerance mechanism of the TAT pathway to phenazines is related to the CCM system, but not due to the ROS scavenging system. Furthermore, respiration-related characteristic tests and peptide analysis suggested that disruption of the TAT complex causes a defect in the cytochrome bc1 complex, which may be involved in the tolerance to phenazines. In summary, this study sheds new light on the critical role of the TAT pathway in influencing the fitness and phenazines tolerance of Xanthomonas species.

In vitro antifungal activity and possible mechanisms of action of chelerythrine.

Chelerythrine (CHE) possesses broad pharmacological activities. In this study, the extract of Chelidonium majus L. were characterized by high performance liquid chromatography (HPLC), infrared radiation (IR) spectroscopy and nuclear magnetic resonance (NMR). It was proved that the extract was CHE. The antifungal activity of CHE against five fungal pathogens of rice was researched in vitro, revealing that CHE inhibited Ustilaginoidea virens (U. virens) and Cochliobolus miyabeanus (C. miyabeanus) with 50% effective concentrations (EC50) of 6.53 × 10-3 mg/mL and 5.62 × 10-3 mg/mL, respectively. When the concentration of CHE was 7.5 × 10-3 mg/mL, the inhibition rate of U. virens reached 56.1%. Moreover, CHE (4 × 10-3 mg/mL) exhibited the greatest efficacy in inhibiting spore of U. virens growth with an inhibition rate as high as 86.7%. CHE displayed the best inhibitory activity against U. virens at the concentration of 7.5 × 10-3 mg/mL, compared with the other two isoquinoline alkaloids and commercial fungicide validamycin. After treating U. virens mycelia with CHE, twisted and atrophied mycelia were observed by optical microscopy. SEM results demonstrated narrow and locally fractured mycelium. TEM observations showed that the cell wall had become thin and broken, and most organelles were difficult to recognize. Furthermore, membrane of mycelia was destroyed and reactive oxygen species (ROS) of spores was accumulated, which induced apoptosis of pathogenic fungi. From these results, our understanding of the mechanisms of antifungal activity of CHE against U. virens was enriched and this research is relevant for developing novel pesticides.

Schaftoside alleviates HFD-induced hepatic lipid accumulation in mice via upregulating farnesoid X receptor.

ETHNOPHARMACOLOGY RELEVANCE: The farnesoid X receptor (FXR) is a therapeutic target of for the treatment of non-alcoholic fatty liver disease (NAFLD) owing to its regulatory role in lipid homeostasis. Schaftoside (SS) is a bioactive compound of Herba Desmodii Styracifolii, which has traditionally been used to treat hepatitis and cholelithiasis. However, the potential hepatoprotective effect of SS against NAFLD and the underlying mechanisms remain unknown. AIM OF THE STUDY: We investigated whether SS could improve NAFLD-induced liver injury by decreasing lipid accumulation via the activation of FXR signalling. MATERIALS AND METHODS: In vivo, the effects of SS on high-fat diet (HFD)-induced lipid accumulation in the liver of mice were evaluated by serum biochemical parameters and histopathological analysis. In vitro, the intracellular triglyceride (TG) level and Oil Red O staining were used to evaluate the lipid removal ability of SS in Huh-7 cells or FXR knockout mouse primary hepatocytes (MPHs) induced by oleic acid (OA). Moreover, FXR/sterol regulatory element-binding protein 1 (SREBP1) mRNA and protein expression levels were detected. RESULTS: SS reduced HFD-induced lipid accumulation in the liver, as indicated by decreased aspartate aminotransferase (AST), cholesterol (Ch), and TG levels in serum and TG levels in liver tissue, and subsequently resulting in attenuation of liver histopathological injury. Gene expression profiles demonstrated that SS dose-dependently prevented HFD-induced decrease of FXR expression and inversely inhibited SREBP1 expression in the nucleus. Furthermore, SS significantly suppressed excessive TG accumulation and decreased intracellular TG level in Huh-7 cells or MPHs via the upregulation of FXR and inhibition of SREBP1 expression in the nucleus. CONCLUSION: Our results suggest that SS ameliorates HFD-induced NAFLD by the decrease of lipid accumulation via the control of FXR-SREBP1 signalling.

Activation of Farnesoid X Receptor by Schaftoside Ameliorates Acetaminophen-Induced Hepatotoxicity by Modulating Oxidative Stress and Inflammation.

Aims: Acetaminophen (APAP) overdose leads to acute liver injury by inducing hepatic mitochondrial oxidative stress and inflammation. However, the molecular mechanisms involved are still unclear. Farnesoid X receptor (FXR) serves as a therapeutic target for the treatment of liver disorders, whose activation has been proved to protect APAP-induced hepatotoxicity. In this study, we examined whether FXR activation by schaftoside (SS), a naturally occurring flavonoid from Desmodium styracifolium, could protect mice against APAP-induced hepatotoxicity via regulation of oxidative stress and inflammation. Results: We first found that SS exhibited potent protective effects against APAP-induced hepatotoxicity in mice. The study reveals that SS is a potential agonist of FXR, which protects mice from hepatotoxicity mostly via regulation of oxidative stress and inflammation. Mechanistically, the hepatoprotective SS is associated with the induction of the genes of phase II detoxifying enzymes (e.g., UGT1A1, GSTα1), phase III drug efflux transporters (e.g., bile salt export pump, organic solvent transporter protein ß), and glutathione metabolism-related enzymes (e.g., glutamate-cysteine ligase modifier subunit [Gclm], glutamate-cysteine ligase catalytic subunit [Gclc]). More importantly, SS-mediated FXR activation could fine-tune the pro- and anti-inflammatory eicosanoids generation via altering eicosanoids metabolic pathway, thereby resulting in decrease of hepatic inflammation. In contrast, FXR deficiency can abrogate the above effects. Innovation and Conclusion: Our results provided the direct evidence that FXR activation by SS could attenuate APAP-induced hepatotoxicity via inhibition of nuclear factor kappa-B signaling and fine-tuning the generation of proinflammatory mediators' eicosanoids. Our findings indicate that strategies to activate FXR signaling in hepatocytes may provide a promising therapeutic approach to alleviate liver injury induced by APAP overdose.