Pyridine-Based Covalent Organic Frameworks with Pyridyl-Imine Structures for Boosting Photocatalytic H2O2 Production via One-Step 2e- Oxygen Reduction.

Bipyridine-based covalent organic frameworks (COFs) have emerged as promising contenders for the photocatalytic generation of hydrogen peroxide (H2O2). However, the presence of imine nitrogen alters the mode of H2O2 generation from an efficient one-step two-electron (2e-) route to a two-step 2e- oxygen reduction pathway. In this work, we introduce 3,3'-bipyridine units into imine-based COF skeletons, creating a pyridyl-imine structure with two adjacent nitrogen atoms between the pyridine ring and imine linkage. This unique bipyridine-like architecture can effectively suppress the two-step 2e- ORR process at the single imine-nitrogen site, facilitating a more efficient one-step 2e- pathway. Consequently, the optimized pyridyl-imine COF (PyIm-COF) exhibits a remarkable H2O2 production rate of up to 5850 µmol h-1 g-1, nearly double that of pristine bipyridine COFs. This work provides valuable insight into the rational design of functionalized COFs for enhanced H2O2 production in photocatalysis.

Monitoring dynamics of Kyagar Glacier surge and repeated draining of Ice-dammed lake using multi-source remote sensing.

Glacier surges, a primary factor contributing to various glacial hazards, has long captivated the attention of the global glaciological community. This study delves into the dynamics of Kyagar Glacier surging and the associated drainage features of its Ice-dammed lake, employing high temporal resolution optical imagery. Our findings indicate that the surge on Kyagar Glacier began in late spring and early summer of 2014 and concluded during the summer of 2016. This surge resulted in the transfer of 0.321 ± 0.012 km3 of glacier mass from the reservoir zone to the receiving zone, leading to the formation of an ice-dammed lake at the glacier's terminus. The lake experienced five outbursts between 2015 and 2019, with the largest discharge occurring in 2017. And the maximum water depth during this period was 112 ± 11 m, resulting in a water storage volume of (158.37 ± 28.32) × 106 m3. On the other hand, our analysis of the relationship between glacier surface velocity and albedo, coupled with an examination of subglacial dynamics, revealed that increased precipitation during the active phase of the Kyagar Glacier results in accumulation of mass in the upper glacier. This accumulation induces changes in basal shear stress, triggering the glacier's transition into an unstable state. Consequently, glacier deformation rates escalate, surface crevasses proliferate, potentially providing conduits for surface meltwater to infiltrate the glacier bed. This, in turn, leaded to elevated basal water pressure, initiating glacier sliding. Furthermore, we postulated that the repetitive drainage of Kyagar Ice-dammed lake was primarily influenced by the opening and closing of subglacial drainage pathways and variations in inflow volumes. Future endeavors necessitate rigorous field observations to enhance glacier surge simulations, deepening our comprehension of glacier surge mechanisms and mitigating the impact of associated glacial hazards.

A randomized proof-of-mechanism trial of TNF antagonism for motivational anhedonia and related corticostriatal circuitry in depressed patients with high inflammation.

Chronic, low-grade inflammation has been associated with motivational deficits in patients with major depression (MD). In turn, impaired motivation has been linked to poor quality of life across psychiatric disorders. We thus determined effects of the anti-inflammatory drug infliximab-a potent tumor necrosis factor (TNF) antagonist-on behavioral and neural measures of motivation in 42 medically stable, unmedicated MD patients with a C-reactive protein > 3mg/L. All patients underwent a double-blind, placebo-controlled, single-dose, randomized clinical trial with infliximab (5mg/kg) versus placebo. Behavioral performance on an effort-based decision-making task, self-report questionnaires, and neural responses during event-related functional magnetic resonance imaging were assessed at baseline and 2 weeks following infusion. We found that relative to placebo, patients receiving infliximab were more willing to expend effort for rewards. Moreover, increase in effortful choices was associated with reduced TNF signaling as indexed by decreased soluble TNF receptor type 2 (sTNFR2). Changes in effort-based decision-making and sTNFR2 were also associated with changes in task-related activity in a network of brain areas, including dmPFC, ventral striatum, and putamen, as well as the functional connectivity between these regions. Changes in sTNFR2 also mediated the relationships between drug condition and behavioral and neuroimaging measures. Finally, changes in self-reported anhedonia symptoms and effort-discounting behavior were associated with greater responses of an independently validated whole-brain predictive model (aka "neural signature") sensitive to monetary rewards. Taken together, these data support the use of anti-inflammatory treatment to improve effort-based decision-making and associated brain circuitry in depressed patients with high inflammation.

Yiqi Jiedu Xiaoying Decoction Improves Experimental Autoimmune Thyroiditis in Rats by Regulating Th17/Treg Cell Balance.

BACKGROUND: Experimental autoimmune thyroiditis (EAT) is a widely used animal model to study the pathogenesis and treatment of autoimmune thyroid diseases. Yiqi Jiedu Xiaoying Decoction (YJXD) is a traditional Chinese medicine formula with potential immunomodulatory effects. In this study, we investigated the therapeutic effects of YJXD on EAT in rats and explored its underlying mechanisms. METHODS: Female Wistar rats were induced to develop EAT by immunization with thyroglobulin (Tg) and taken sodium iodide water (0.05%) and then treated with YJXD or sodium selenite. HE staining was used to observe the pathological changes of thyroid tissue in EAT rats. Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expression levels of Th17- and Treg-related cytokines and thyroid autoantibody were determined by enzyme-linked immunosorbent assay (ELISA). The expression of Th17- and Treg-related transcriptional factors was detected by real-time polymerase chain reaction (RT-PCR) and Immunohistochemistry (IHC). RESULTS: Our results demonstrated that treatment with YJXD significantly attenuated the severity of EAT, as evidenced by reduced thyroid gland inflammatory infiltration and decreased serum thyroglobulin autoantibody levels. Importantly, YJXD treatment effectively modulated the Th17/Treg cell balance by suppressing Th17 cell differentiation and promoting Treg cell expansion. Moreover, YJXD was also found to regulate the expression levels of Th17- and Tregrelated cytokines and transcriptional factors, further supporting its immunomodulatory effects in EAT. CONCLUSION: YJXD exerted therapeutic effects on EAT by regulating the Th17/Treg cell balance, modulating the production of Th17- and Treg-related cytokines and the expression of transcriptional factors.

Dynamics of algal blooms in typical low-latitude plateau lakes: Spatiotemporal patterns and driving factors.

The alpine lakes distributed on the plateau are crucial for the hydrological, and biogeochemical cycle, and also serve as a guarantee for regional economic development and human survival. However, under the influence of human interference and climate fluctuations, lakes are facing problems of eutrophication and subsequent algal blooms (ABs) with acceleration, and the development and driving factors of this phenomenon need to be considered as a whole. In this study, ten lakes located on the Yunnan-Guizhou Plateau were selected as the study area to analyze the spatiotemporal distribution of ABs and possible controlling forces. The FAI (Floating Algae Index) derived from multiple MODIS products and water quality data under high-frequency monitoring were selected as the data sources for characterizing ABs. Three nutrient parameters and five meteorological variables were used to explore the driving factors affecting ABs. Various methods of trend detection and correlation analysis have been applied. The main results are as follows: (1) Dianchi Lake (in lake area) and Xingyun Lake (in area proportion) are the two lakes with the most serious ABs in the historical period; (2) ABs are mainly distributed on the shoreline and northern edge of lakes, and tend to stay away from the lake center during high-temperature periods of the day; (3) Six lakes show a decreasing trend in ABs, especially after 2018, while other lakes (including Fuxian, Chenghai, Yangzong, and Erhai) are increasing, not only in peak value but also in duration; (4) Lakes with severe ABs are all P-restricted lakes, the minimum temperature is the most sensitive meteorological factor, while the impact of precipitation against ABs has a time lag; (5) Establishing a warning system of temperature and nutrient concentration is critical in ABs adaptive strategy. This study is expected to provide scientific references for regional water management and the restoration of the eutrophic aquatic ecosystem.

In Vivo Characterization of Cerebellar Peduncles in Chronic Ankle Instability: A Single and Multishell Diffusion-Weighted Imaging Study.

BACKGROUND: Ankle sprain causes proprioceptor injuries and prolonged joint deafferentation, which might lead to maladaptive neuroplasticity in patients with chronic ankle instability (CAI), especially in the cerebellum. Previous studies have indicated the impairment of superior cerebellar peduncle (SCP), but the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) have not been fully analyzed. HYPOTHESIS: The cerebellar peduncles of participants with CAI would have altered fractional anisotropy (FA) and orientation dispersion index (ODI) in comparison with healthy controls without ankle injury history. In addition, FA and ODI would be correlated with the duration or severity of the sensorimotor deficits in CAI. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: A group of 27 participants with CAI and 26 healthy controls underwent diffusion-weighted imaging scanning, with the cerebellar peduncles as the regions of interest. The measures obtained by single-shell diffusion tensor imaging and the multishell neurite orientation dispersion and density imaging were used. Correlation analyses were performed to examine the potential relationship between the FA/ODI and both the normalized Y-balance scores and the durations of ankle instability. RESULTS: The ipsilateral ICP of the injured ankle in participants with CAI showed significantly lower FA (Cohen d 95% CI, -1.33 to -0.21; P = 0.04) and marginally significant higher ODI (Cohen d 95% CI, 0.10 to 1.20, P = 0.08) when compared with the same measures in the control group, with the ODI being positively correlated with the duration of ankle instability (r = 0.42, P = 0.03). CONCLUSION: The ICP in participants with CAI exhibited impaired integrity and a trend of abnormally organized neurites in comparison with a healthy control group. CLINICAL RELEVANCE: The impairments of ICP might be an ongoing part of the pathological process of CAI, having the potential to become a target for the diagnostic evaluation of this clinical entity.

Construction of Covalent Organic Framework Nanofiber Membranes for Efficient Adsorption of Antibiotics.

Techniques beyond crystal engineering are critical for manufacturing covalent organic frameworks (COFs) and to explore them for advanced applications. However, COFs are normally obtained as insoluble, unmeltable, and thus nonprocessible microcrystalline powders. Therefore, it is a significant challenge to implement COFs into larger architectures and structural control on different length scales. Herein, a facile strategy is presented to prepare flexible COF nanofiber membranes by in-situ growth of COFs on polyacrylonitrile (PAN) nanofiber substrates via a reversible polycondensation-termination approach. The obtained PAN@COF nanofiber membranes with vertically aligned COF nanoplates combine a large functional surface with efficient mass transport, thus making it a promising adsorbent, for example, for water purification. The antibiotic pollutant ofloxacin (OFX) is removed from water with a superior absorption capacity of ≈236 mg g-1 and removal efficiency as high as 98%. The here presented in-situ growth of COFs on nanofiber membranes can be extended to various Schiff base-derived COF materials with different compositions, providing a highly efficient way to construct flexible COF-based membranes for several applications.

Quantitative Magnetic Resonance Imaging-Based Tendon Healing of Different Regions of the Shoulder: Comparison Between the Suture-Bridge and Single-Row Techniques.

Background: Rotator cuff retears occur more often at the proximal region with the suture-bridge (SB) technique than at the typical footprint region with the single-row (SR) technique. Few longitudinal clinical trials have focused on the postoperative tendon quality of the repaired rotator cuff at different regions between the 2 techniques. Purpose: To compare tendon healing of the proximal and distal regions between the SB and SR techniques. Study Design: Cohort study; Level of evidence, 3. Methods: Included were consecutive patients who underwent arthroscopic rotator cuff repair and undertook clinical and magnetic resonance imaging (MRI) examinations at 3, 6, and 12 months postoperatively between 2016 and 2017. These patients were divided into the SB and SR groups according to the technique used. The repaired tendon was segmented into distal and proximal regions on ultrashort echo time-T2* mapping images. Clinical outcomes (Constant score, American Shoulder and Elbow Surgeons score, Fudan University Shoulder Score, and visual analog scale for pain) and MRI-based tendon healing (T2* values) of different regions were compared between the 2 groups. The differences in T2* values and clinical scores were determined by 1-way analysis of variance for repeated measurements. Results: A total of 31 patients (17 in SB group and 14 in SR group) were included. At 12-month follow-up, significant improvements from preoperatively were achieved for all patients in all clinical scores (P < .001 for all). No significant between-group differences were found in T2* values of the distal region at any time point; however, the mean T2* value of the proximal region at 3 months was significantly higher in the SB group compared with the SR group (P = .03). This difference became nonsignificant at subsequent follow-up time points. Conclusion: Significant clinical improvements over time can be expected in the first year after arthroscopic rotator cuff repair. In the early postoperative period, higher T2* values in the proximal region of the repaired tendon (representing inferior tendon quality) were seen with the SB technique compared with the SR technique; however, this phenomenon was resolved over time.

Discovery of cysteine-targeting covalent histone methyltransferase inhibitors.

Post-translational methylation of histone lysine or arginine residues by histone methyltransferases (HMTs) plays crucial roles in gene regulation and diverse physiological processes and is implicated in a plethora of human diseases, especially cancer. Therefore, histone methyltransferases have been increasingly recognized as potential therapeutic targets. Consequently, the discovery and development of histone methyltransferase inhibitors have been pursued with steadily increasing interest over the past decade. However, the disadvantages of limited clinical efficacy, moderate selectivity, and propensity for acquired resistance have hindered the development of HMTs inhibitors. Targeted covalent modification represents a proven strategy for kinase drug development and has gained increasing attention in HMTs drug discovery. In this review, we focus on the discovery, characterization, and biological applications of covalent inhibitors for HMTs with emphasis on advancements in the field. In addition, we identify the challenges and future directions in this fast-growing research area of drug discovery.

A covalent organic framework/graphene aerogel electrocatalyst for enhanced overall water splitting.

The rational design of covalent organic framework (COF) based hybrid materials is of paramount importance to address the fundamental challenges of COFs with respect to their poor electron mobilization and the limited number of accessible active sites. Herein, we propose a new strategy for the fabrication of covalently bonded COF grafted graphene aerogel hybrid materials for electrocatalytic application. An in situ step-growth polymerization approach was developed to achieve the hybridization of COFs along the surface of amino-functionalized graphene nanosheets. By taking advantage of the three-dimensional conductive networks and highly accessible active sites, the cobalt-incorporated COF/graphene hybrid aerogel shows high oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) performances with an overpotential of 300 and 275 mV at 10 mA cm-2, respectively, under alkaline conditions. When applied to an electrochemical water-splitting electrolyzer, it is able to produce hydrogen and oxygen at competitive rates of 1.14 and 0.58 µL s-1, respectively, under ambient conditions, demonstrating its potential for practical applications.

Globally elevated chemical weathering rates beneath glaciers.

Physical erosion and chemical weathering rates beneath glaciers are expected to increase in a warming climate with enhanced melting but are poorly constrained. We present a global dataset of cations in meltwaters of 77 glaciers, including new data from 19 Asian glaciers. Our study shows that contemporary cation denudation rates (CDRs) beneath glaciers (2174 ± 977 Σ*meq+ m-2 year-1) are ~3 times higher than two decades ago, up to 10 times higher than ice sheet catchments (~150-2000 Σ*meq+ m-2 year-1), up to 50 times higher than whole ice sheet means (~30-45 Σ*meq+ m-2 year-1) and ~4 times higher than major non-glacial riverine means (~500 Σ*meq+ m-2 year-1). Glacial CDRs are positively correlated with air temperature, suggesting glacial chemical weathering yields are likely to increase in future. Our findings highlight that chemical weathering beneath glaciers is more intense than many other terrestrial systems and may become increasingly important for regional biogeochemical cycles.

Saponins of Momordica charantia increase insulin secretion in INS-1 pancreatic ß-cells via the PI3K/Akt/FoxO1 signaling pathway.

Saponins are the main bioactive substances with anti-hyperglycemic activities of Momordica charantia. This study aimed to verify the effects of M. charantia saponins on insulin secretion and explore the potential underlying mechanisms in INS-1 pancreatic ß-cells. We injured INS-1 cells with 33.3mM glucose and then treated them with saponins. Saponins improved cell morphology and viability as demonstrated by inverted microscopy and CCK8 detection and significantly increased insulin secretion in a concentration-dependent manner as shown by ELISA. Thus, we obtained the optimal concentration for the subsequent experiments. Potential mechanisms were explored by immunofluorescence, western blotting, and RT-qPCR techniques. First, saponins increased the mRNA and protein levels of IRS-2 but decreased the serine 731 phosphorylation level of IRS-2. Moreover, saponins increased the phosphorylation of Akt protein and decreased the protein level of FoxO1, which were both reversed by the PI3K inhibitor ly294002. Furthermore, saponins increased the protein level of the downstream molecule and insulin initiating factor PDX-1, which was also reversed by ly294002. Saponins also increased Akt and PDX-1 mRNA and decreased FoxO1 mRNA, which were both reversed by ly294002. Saponins increased glucose-stimulated insulin secretion (GSIS) and intracellular insulin content, which were reversed by ly294002, as determined by ELISA. The immunofluorescence results also confirmed this tendency. In conclusion, our findings improve our understanding of the function of saponins in INS-1 pancreatic ß-cells and suggest that saponins may increase insulin secretion via the PI3K/Akt/FoxO1 signaling pathway.

Overview of terrestrial water storage changes over the Indus River Basin based on GRACE/GRACE-FO solutions.

Water resources are under severe stress in the highly populated Indus River Basin due to the increased consumption of water across different sectors and climate change. Coping with these challenges, requires a clear understanding on hydrological processes and anthropogenic activities, and how these are influencing recharging and spatiotemporal availability of groundwater in the basin. The present study aims to investigate the natural and anthropogenic impact on Terrestrial Water Storage (TWS) over the Indus River Basin by using a series of statistical methods and the observation data from the Gravity Recovery and Climate Experiment (GRACE) and Follow-On (GRACE-FO). Our results show that (i) TWS Anomaly (TWSA) experienced a significant decrease from 2002 to 2020, particularly in the MUIP; (ii) the UIB showed a weak decreasing trend in TWSA as a result of the accelerated glacier melting; (iii) there was significant loss of groundwater (1.57 mm/month) caused by ineffective water management and over-exploitation; and (iv) assisted by favorable meteorological conditions, the precipitation presented a positive trend against the weakness of the Westerlies, which exerted the positive influence on TWSA.

Saponins of Momordica charantia increase insulin secretion in INS-1 pancreatic ß-cells via the PI3K/Akt/FoxO1 signaling pathway.

Saponins are the main bioactive substances with anti-hyperglycemic activities of Momordica charantia. This study aimed to verify the effects of M. charantia saponins on insulin secretion and explore the potential underlying mechanisms in INS-1 pancreatic ß-cells. We injured INS-1 cells with 33.3mM glucose and then treated them with saponins. Saponins improved cell morphology and viability as demonstrated by inverted microscopy and CCK8 detection and significantly increased insulin secretion in a concentration-dependent manner as shown by ELISA. Thus, we obtained the optimal concentration for the subsequent experiments. Potential mechanisms were explored by immunofluorescence, western blotting, and RT-qPCR techniques. First, saponins increased the mRNA and protein levels of IRS-2 but decreased the serine 731 phosphorylation level of IRS-2. Moreover, saponins increased the phosphorylation of Akt protein and decreased the protein level of FoxO1, which were both reversed by the PI3K inhibitor ly294002. Furthermore, saponins increased the protein level of the downstream molecule and insulin initiating factor PDX-1, which was also reversed by ly294002. Saponins also increased Akt and PDX-1 mRNA and decreased FoxO1 mRNA, which were both reversed by ly294002. Saponins increased glucose-stimulated insulin secretion (GSIS) and intracellular insulin content, which were reversed by ly294002, as determined by ELISA. The immunofluorescence results also confirmed this tendency. In conclusion, our findings improve our understanding of the function of saponins in INS-1 pancreatic ß-cells and suggest that saponins may increase insulin secretion via the PI3K/Akt/FoxO1 signaling pathway.

Spatiotemporal variability of glacier changes and their controlling factors in the Kanchenjunga region, Himalaya based on multi-source remote sensing data from 1975 to 2015.

Spatio-temporal behavior of glaciers in the Himalayas has varied greatly in response to reported climate warming and other modulating factors such as topography, debris cover, and glacier morphology. In this paper, 429 glaciers were examined in the Kanchenjunga region in the middle of the Himalayas. Geodetic methods, feature-based image matching, and multi-parametric integrated approaches were used to detect differences of glacier change and the dominant characteristics driving these differences based on digital elevation models (DEMs), Landsat TM/ETM+/OLI images, Envisat/ASAR and Sentinel-1 data. The results showed that the average change rates in glacier area and surface elevation in 1975-2015 were -0.18 ± 0.07% a-1 and - 0.32 ± 0.02 m a-1, respectively. The rates of areal shrinkage of glaciers and the glacier surface velocity on the northern side of the Himalayan crest were 1.25 and 1.7 times larger than those of the glaciers on the southern slopes, respectively, whereas the rates of glacier thinning were lower in the north than in the south. The temperature increase from 1975 to 2015 caused an overall widespread glacier retreat in the region. However, differences in the topography of the Kanchenjunga region led to spatial variability in glacier changes with discrepancies as large as several times. The features of individual glaciers, such as glacier size, debris cover, and development of ice-contact glacial lakes enhanced the local complexity of glacier change and elusive response behaviors of the glaciers to climate warming led by the different topographic conditions.

Pseudomonas sp. ST4 produces variety of active compounds to interfere fungal sexual mating and hyphal growth.

Sexual mating of compatible sporida is essential for Sporisorium scitamineum to form dikaryotic mycelia and then cause infection on sugarcane. Our previous work identified a Pseudomonas sp. ST4 from a soil sample, which showed a promising biocontrol potential by inhibiting the mating of S. scitamineum sporida and hyphal growth. In this study, we set to isolate the active compounds from Pseudomonas sp. ST4 through solid fermentation. High-performance liquid chromatography (HPLC) separation coupling with bioassay showed that Pseudomonas sp. ST4 produced a range of antimicrobial compounds. Two of the major components were purified following acetate extraction, silica gel and HPLC separation. Nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS) analysis identified these active compounds are 4-hydroxybenzaldehyde and indole-3-carbaldehyde respectively. Further analysis showed that the former compound only inhibited the hyphal growth of the fungus at a concentration of 3 mM, while the latter interfered the fungal sexual mating at a concentration of 0.6 mM and affected hyphal growth at a concentration of 2 mM. Treatment of corn plants with 3 mM indole-3-carbaldehyde significantly inhibited corn smut infection, with a control rate up to 94%. Further analysis of the structure and activity relationship revealed that indole has a much stronger inhibitory activity against the fungal sexual mating than indole-3-carbaldehyde. The results from this study provide new agents for control and prevention of the sugarcane smut disease, and the active compounds could also be used to probe the molecular mechanisms of fungal sexual mating.

Fluctuation analysis in the dynamic characteristics of continental glacier based on Full-Stokes model.

Ice thickness has a great influence on glacial movement and ablation. Over the course of the change in thickness, area and external climate, the dynamic process of how glaciers change and whether a glacier's changes in melting tend to be stable or irregular is a problem that needs to be studied in depth. In our study, the changes in the dynamic process of the No. 8 Glacier in Hei Valley (H8) under the conditions of different thicknesses in 1969 and 2009 were simulated based on the Full-Stokes code Elmer/Ice (http://www.csc.fi/elmer/). The results were as follows: (1) The thickness reduction in glaciers would lead to a decrease in ice surface tension and basal pressure and friction at the bottom, and the resulting extensional and compressional flow played an important role in the variations in glacial velocity. (2) The force at the bottom of the glacier was key to maintaining the overall stress balance, and the glaciers that often melted and collapsed in bedrock were more easily destroyed by the overall force balance and increased change rate of glacial thaw. (3) Temperature changes at different altitudes affected the ice viscous force. The closer the ice surface temperature was to the melting point, the greater the influence of temperature changes on the ice viscous force and ice surface velocity. Finally, we used the RCP 4.8 and 8.5 climate models to simulate the changes in H8 over the next 40 years. The results showed that with some decreases in ice surface compression and tension, the gravity component changes caused by local topography begin to control the ice flow movement on the surface of glacier, and melting of the glacial surface will appear as an irregular change. The simulation results further confirmed that the fluctuation in glacial dynamic characteristics could be attributed to the change in the gravity component caused by ablation.

Biocontrol of Sugarcane Smut Disease by Interference of Fungal Sexual Mating and Hyphal Growth Using a Bacterial Isolate.

Sugarcane smut is a fungal disease caused by Sporisorium scitamineum, which can cause severe economic losses in sugarcane industry. The infection depends on the mating of bipolar sporida to form a dikaryon and develops into hyphae to penetrate the meristematic tissue of sugarcane. In this study, we set to isolate bacterial strains capable of blocking the fungal mating and evaluate their potential in control of sugarcane smut disease. A bacterial isolate ST4 from rhizosphere displayed potent inhibitory activity against the mating of S. scitamineum bipolar sporida and was selected for further study. Phylogenetic analyses and biochemical characterization showed that the isolate was most similar to Pseudomonas guariconensis. Methanol extracts from minimum and potato dextrose agar (PDA) agar medium, on which strain ST4 has grown, showed strong inhibitory activity on the sexual mating of S. scitamineum sporida, without killing the haploid cells MAT-1 or MAT-2. Further analysis showed that only glucose, but not sucrose, maltose, and fructose, could support strain ST4 to produce antagonistic chemicals. Consistent with the above findings, greenhouse trials showed that addition of 2% glucose to the bacterial inoculum significantly increased the strain ST4 biocontrol efficiency against sugarcane smut disease by 77% than the inoculum without glucose. The results from this study depict a new strategy to screen for biocontrol agents for control and prevention of the sugarcane smut disease.

Genetic Modulation of c-di-GMP Turnover Affects Multiple Virulence Traits and Bacterial Virulence in Rice Pathogen Dickeya zeae.

The frequent outbreaks of rice foot rot disease caused by Dickeya zeae have become a significant concern in rice planting regions and countries, but the regulatory mechanisms that govern the virulence of this important pathogen remain vague. Given that the second messenger cyclic di-GMP (c-di-GMP) is associated with modulation of various virulence-related traits in various microorganisms, here we set to investigate the role of the genes encoding c-di-GMP metabolism in the regulation of the bacterial physiology and virulence by construction all in-frame deletion mutants targeting the annotated c-di-GMP turnover genes in D. zeae strain EC1. Phenotype analyses identified individual mutants showing altered production of exoenzymes and phytotoxins, biofilm formation and bacterial motilities. The results provide useful clues and a valuable toolkit for further characterization and dissection of the regulatory complex that modulates the pathogenesis and persistence of this important bacterial pathogen.

Quorum sensing and microbial drug resistance.

Microbial drug resistance has become a serious problem of global concern, and the evolution and regulatory mechanisms of microbial drug resistance has become a hotspot of research in recent years. Recent studies showed that certain microbial resistance mechanisms are regulated by quorum sensing system. Quorum sensing is a ubiquitous cell-cell communication system in the microbial world, which associates with cell density. High-density microbial cells produce sufficient amount of small signal molecules, activating a range of downstream cellular processes including virulence and drug resistance mechanisms, which increases bacterial drug tolerance and causes infections on host organisms. In this review, the general mechanisms of microbial drug resistance and quorum-sensing systems are summarized with a focus on the association of quorum sensing and chemical signaling systems with microbial drug resistance mechanisms, including biofilm formation and drug efflux pump. The potential use of quorum quenching as a new strategy to control microbial resistance is also discussed.