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The intracellular bacterial pathogen Legionella pneumophila utilizes the Dot/Icm system to translocate over 330 effectors into the host cytosol. These virulence factors modify a variety of cell processes, including pathways involved in cell death and survival, to promote bacterial proliferation. Here, we show that the effector LegK3 is a eukaryotic-like Ser/Thr kinase that functions to suppress host apoptosis. Mechanistically, LegK3 directly phosphorylates multiple caspases involved in apoptosis signaling, including Caspase-3, Caspase-7, and Caspase-9. LegK3-induced phosphorylation of these caspases occurs at serine (Ser29 in Caspase-3 and Ser199 in Caspase-7) or threonine (Thr102 in Caspase-9) residues located in the prodomain or interdomain linkers. These modifications interfere with the suitability of the caspases as the substrates of initiator caspases or upstream regulators without impacting their proteolytic activity. Collectively, our study reveals a novel strategy used by L. pneumophila to maintain the integrity of infected cells for its intracellular growth. The bacterial pathogen Legionella pneumophila delivers hundreds of effector proteins to promote infection. Here, Ge et al show that effector LegK3 suppresses host apoptosis via direct phosphorylation of caspases. [ABSTRACT FROM AUTHOR]

When IL-1 receptor antagonist (IL-1rn) is knocked out, mice have shown strain background dependent and major QTL regulated susceptibility to spontaneously inflammatory arthritis disease (SAD). The impact on bone properties resulting from the interactions of IL-1rn, genomic background strains, and the QTL locus, is unknown. Bone properties in the four specifically bred mouse strains with mutation of IL-1rn and variations in genomic components were investigated with high-resolution MicroCT and genomic analytical tools. Two congenic mouse strains were also measured to evaluate the influence on bone properties by a QTL in the region in chromosome 1. Our results reveal that several bone phenotypes, including bone mineral density (BMD), bone volume, tibial length, and cortical thickness of the tibia are different between wild type and IL-1rn knockout mice in both Balb/c and DBA/1 backgrounds, but IL-1rn knockout affects BMD differently between the two mouse strains. The absence of IL-1rn decreases BMD in Balb/c mice but increases BMD in DBA/1−/− mice compared to their respective wild type counterparts. A QTL transferred from the Balb/c genetic background which affects arthritis in congenic strains appears to also regulate BMD. While several genes, including Ctsg and Prg2, may affect BMD, Ifi202b is the most favored candidate gene for regulating BMD as well as SAD. In conclusion, the previously mentioned bone phenotypes are each influenced in different ways by the loss of IL-1ra when considered in mice from varying genomic backgrounds. [ABSTRACT FROM AUTHOR]

The intracellular bacterial pathogen Legionella pneumophila modulates host cell functions by secreting multiple effectors with diverse biochemical activities. In particular, effectors of the SidE family interfere with host protein ubiquitination in a process that involves production of phosphoribosyl ubiquitin (PR-Ub). Here, we show that effector LnaB converts PR-Ub into ADP-ribosylated ubiquitin, which is further processed to ADP-ribose and functional ubiquitin by the (ADP-ribosyl)hydrolase MavL, thus maintaining ubiquitin homeostasis in infected cells. Upon being activated by actin, LnaB also undergoes self-AMPylation on tyrosine residues. The activity of LnaB requires a motif consisting of Ser, His and Glu (SHxxxE) present in a large family of toxins from diverse bacterial pathogens. Thus, our study sheds light on the mechanisms by which a pathogen maintains ubiquitin homeostasis and identifies a family of enzymes capable of protein AMPylation. The bacterial pathogen Legionella pneumophila secretes effectors that affect protein ubiquitination within host cells, involving production of phosphoribosyl ubiquitin (PR-Ub). Here, the authors identify additional effectors that convert PR-Ub back into functional ubiquitin, thus maintaining ubiquitin homeostasis in infected cells. [ABSTRACT FROM AUTHOR]

AMPylation is a post-translational modification in which AMP is added to the amino acid side chains of proteins1,2. Here we show that, with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity towards the phosphoryl group of phosphoribose on PRR42-Ub that is generated by the SidE family of effectors, and deubiquitinases DupA and DupB in an E1- and E2-independent ubiquitination process3–7. The product of LnaB is further hydrolysed by an ADP-ribosylhydrolase, MavL, to Ub, thereby preventing the accumulation of PRR42-Ub and ADPRR42-Ub and protecting canonical ubiquitination in host cells. LnaB represents a large family of AMPylases that adopt a common structural fold, distinct from those of the previously known AMPylases, and LnaB homologues are found in more than 20 species of bacterial pathogens. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity towards phosphorylated residues and produces unique ADPylation modifications in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family of kinases8,9, which dampens downstream phosphorylation signalling in the host. Structural studies reveal the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study identifies, to our knowledge, an unprecedented molecular regulation mechanism in bacterial pathogenesis and protein phosphorylation.An effector protein called LnaB from Legionella pneumophila catalyses a unique type of AMPylation, and LnaB and its homologues represent a distinct family of AMPylases with specific structural features. [ABSTRACT FROM AUTHOR]

Protein ubiquitination is one of the most important posttranslational modifications (PTMs) in eukaryotes and is involved in the regulation of almost all cellular signaling pathways. The intracellular bacterial pathogen Legionella pneumophila translocates at least 26 effectors to hijack host ubiquitination signaling via distinct mechanisms. Among these effectors, SidC/SdcA are novel E3 ubiquitin ligases with the adoption of a Cys-His-Asp catalytic triad. SidC/SdcA are critical for the recruitment of endoplasmic reticulum (ER)-derived vesicles to the Legionella-containing vacuole (LCV). However, the ubiquitination targets of SidC/SdcA are largely unknown, which restricts our understanding of the mechanisms used by these effectors to hijack the vesicle trafficking pathway. Here, we demonstrated that multiple Rab small GTPases and target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins are bona fide ubiquitination substrates of SidC/SdcA. SidC/SdcA-mediated ubiquitination of syntaxin 3 and syntaxin 4 promotes their unconventional pairing with the vesicle-SNARE protein Sec22b, thereby contributing to the membrane fusion of ER-derived vesicles with the phagosome. In addition, our data reveal that ubiquitination of Rab7 by SidC/SdcA is critical for its association with the LCV membrane. Rab7 ubiquitination could impair its binding with the downstream effector Rab-interacting lysosomal protein (RILP), which partially explains why LCVs avoid fusion with lysosomes despite the acquisition of Rab7. Taken together, our study reveals the biological mechanisms employed by SidC/SdcA to promote the maturation of the LCVs. [ABSTRACT FROM AUTHOR]

Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival. The selective degradation of mitochondria by autophagy is essential for cell homeostasis. Here, Nan et al show that the effector protein BipD, secreted by Burkholderia pseudomallei, is able to modulate host mitophagy to promote its survival. [ABSTRACT FROM AUTHOR]

Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria. Overall, we demonstrate that pathogens have evolved an elaborate strategy to modulate host ubiquitin signaling to evade septin-cage entrapment. Here, Xian et al. use phosphoproteomics to identify that the Shigella effector OspG interacts with a regulator of Cullin-RING ubiquitin ligases to promote the ubiquitination of septins and consequent inhibition of septin cage formation. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) due to their outstanding features, such as unique electronic properties and large specific surface areas, have been intensively studied as nanoscale fillers to improve the permittivity of polymer dielectrics. However, due to the unfavourable formation of conductive channels, these CNTs-derived nanocomposites usually suffer from high dielectric loss and low breakdown strength, therefore greatly restricting their practical applications. In this work, we modified pristine multiwalled carbon nanotubes (MWCNTs) by chemical oxidation to prepare partially unzipped carbon nanotubes (PUCNTs), which not only retained excellent electrical properties but also enhanced interfacial interactions with polymers. The obtained PUCNTs/poly(vinylidene fluoride) (PVDF) nanocomposites exhibit higher permittivity and lower dielectric loss compared to raw MWCNTs added. To further alleviate the detrimental influence of conductive channels, we have designed a new class of hybrid composed of PUCNTs-decorated CaCu3Ti4O12 nanoparticles (PUCNTs-CCTO) and their PVDF-based nanocomposites. At 1 kHz, the PUCNTs-CCTO/PVDF nanocomposite filled the ternary nanocomposites also possess strong resistance to electric field failure and achieve significantly enhanced energy storage capability. With 3 vol% PUCNTs and 30 vol% CCTO, the breakdown strength of the nanocomposite can still be maintained at 125 kV mm−1 and the theoretical maximum energy density reaches to 15.5 J cm−3, which is nearly 3 times compared to neat PVDF (5.1 J cm−3). These merits of the PUCNTs-CCTO/PVDF nanocomposites suggest that the strategy proposed herein is a promising avenue for the development of dielectric materials with high energy storage capacity. [ABSTRACT FROM AUTHOR]

Purpose: The efficacy of immune checkpoint inhibitors such as programmed cell death ligand 1 (PD-L1) antibodies in non-small cell lung cancer (NSCLC) is limited, and combined use with other therapies is recommended. Dipeptidyl peptidase 4 (DPP4) inhibitors, a class of small molecule inhibitors, are highly effective for treating type 2 diabetes. Emerging evidence implicates DPP4 inhibitors as immunomodulators that modify aspects of innate and adaptive immunity. We evaluated the combination of a DPP4 inhibitor (anagliptin) and PD-L1 blockade in an NSCLC mouse model. Methods: The effect of the combination of anti-PD-L1 and anagliptin was evaluated in subcutaneous mouse models of NSCLC. Tumor-infiltrating immune cells were analyzed by flow cytometry. Bone marrow-derived monocytes of C57BL/6 mice were isolated in vitro to examine the underlying mechanism of anagliptin on the differentiation and polarization of macrophage. Results: Anagliptin dramatically improved the efficacy of PD-L1 antibody monotherapy by inhibiting macrophage formation and M2 polarization in the tumor microenvironment. Mechanistically, anagliptin suppressed the production of reactive oxygen species in bone marrow monocytes by inhibiting NOX1 and NOX2 expression induced by macrophage colony-stimulating factor, reduced late ERK signaling pathway activation, and inhibited monocyte-macrophage differentiation. However, the inhibitory effect was reactivated by lipopolysaccharide and interferon-gamma interacting with corresponding receptors during M1 macrophage polarization, but not M2. Conclusions: Anagliptin can enhance PD-L1 blockade efficacy in NSCLC by inhibiting macrophage differentiation and M2 macrophage polarization, and combination therapy may be a promising strategy for treating PD-L1 blockade therapy-resistant patients with NSCLC. [ABSTRACT FROM AUTHOR]

Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9's production. Using an orthotopic mouse model of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in bidirectional crosstalk between pancreatic tumor epithelium and TME and results in a pro-‍tumorigenic contexture. Crosstalk between tumor cells and the microenvironment is essential for tumor progression. Here, the authors show Pancreatic ductal adenocarcinoma (PDAC) epithelial cells with high level of Lin28b secrete Wnt5a to upregulate Lin28b expression in cancer-associated fibroblasts, which in turn promote growth of PDAC cells via production of PCSK9. [ABSTRACT FROM AUTHOR]

Objectives : Periodontitis is accompanied by attachment loss and alveolar bone resorption. Vitamin D (VD) deficiency was closely associated with bone loss or osteoporosis. The study aims to investigate the potential relationship between different VD levels and severe periodontal attachment loss in American adults. Methods: A cross-sectional analysis was conducted including 5749 participants in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. The association of periodontal attachment loss progression with total VD, vitamin D3 (VD3), and vitamin D2 (VD2) levels was assessed using multivariable linear regression models, hierarchical regression, fitted smoothing curves, and generalized additive models. Results: Based on the indicators of 5749 subjects, we found that severe attachment loss tended to occur in the elderly or males and was accompanied by less total VD levels, or VD3 levels, as well as a lower poverty-income ratio (PIR). Total VD (below the inflection point: 111 nmol/L) or VD3 were negatively associated with the progression of attachment loss in each multivariable regression model. In threshold analysis, VD3 is linearly correlated with the progression of attachment loss (β = − 0.0183, 95% CI: − 0.0230 to − 0.0136). The relationship between VD2 and attachment loss progression was an S-shaped curve (inflection point: 5.07 nmol/L). Conclusion: Increasing total VD (below 111 nmol/L) and VD3 levels may be beneficial to periodontal health. VD2 levels above 5.07 nmol/L were a risk factor for severe periodontitis. Clinical relevance: The present study reports that different vitamin D levels may serve as different associations with periodontal attachment loss progression. [ABSTRACT FROM AUTHOR]

Improving the compatibility and dispersion between nanoparticles and polymers has become the key to enhance the dielectric properties. In addition, dielectric materials should also have excellent dielectric and thermal stability to meet the application under extreme conditions. Herein, we synthesized a core–shell structure BST@HBPI and BST@HBPI/PEI nanocomposite films. HBPI owns a chemical structure similar to polyetherimide (PEI), and the dipole moment of the polar group contained in it is small, so it can enhance the interface interaction between the nanoparticles and the matrix, hence effectively inhibiting the free charge, and reducing the leakage current in composite. The results show that the introduction of HBPI not only effectively improves the compatibility and dispersion of nanoparticles and polymer matrix, but also greatly enhances the dielectric properties and energy storage properties of nanocomposites. Under an electric field of 200 kV mm−1, the minimum charge-discharge efficiency of BST@HBPI/PEI reaches 74.36%, which is 1.33 times of that for BST/PEI (55.97%), and the maximum discharge energy density reaches 5.01 J cm−3, which is 1.28 times comparing to BST/PEI (3.89 J cm−3). Meanwhile, due to the preeminent electrothermal stability of nanoparticles and matrix, nanocomposites can maintain excellent dielectric properties at high temperatures. The dielectric constant of 10 vol% BST@HBPI/PEI (7.56 J cm−3) is 93.24% at 25 °C (8.113 J cm−3) while the dielectric loss at 200 °C (0.04287) is 114.29% when comparing to that at 25 °C (0.03751). This work provides a promising method for manufacturing dielectric materials that can work in extreme environments. [ABSTRACT FROM AUTHOR]

Main conclusion: LncRNAs regulate flower color formation in Ipomoea nil via vacuolar pH, TCA cycle, and oxidative phosphorylation pathways. The significance of long noncoding RNA (lncRNA) in diverse biological processes is crucial in plant kingdoms. Although study on lncRNAs has been extensive in mammals and model plants, lncRNAs have not been identified in Ipomoea nil (I. nil). In this study, we employed whole transcriptome strand-specific RNA sequencing to identify 11,203 expressed lncRNA candidates, including 961 known lncRNA and 10,242 novel lncRNA in the I. nil genome. These lncRNAs in I. nil had fewer exons and were generally shorter in length compared to mRNA genes. Totally, 1141 different expression lncRNAs (DELs) were significantly identified between white and red flowers. The functional analysis indicated that lncRNA-targeted genes were enriched in the TCA cycle, photosynthesis, and oxidative phosphorylation-related pathway, which was also found in differentially expressed genes (DEGs) functional enrichments. LncRNAs can regulate transcriptional levels through cis- or trans-acting mechanisms. LncRNA cis-targeted genes were significantly enriched in potassium and lysosome. For trans-lncRNA, two energy metabolism pathways, TCA cycles and oxidative phosphorylation, were identified from positive association pairs of trans-lncRNA and mRNA. This research advances our understanding of lncRNAs and their role in flower color development, providing valuable insights for future selective breeding of I. nil. [ABSTRACT FROM AUTHOR]

Introduction: Heat is generated and transferred to the dentine-pulp complex during various dental procedures, such as from friction during cavity preparations, exothermic reactions during the polymerisation of restorative materials and when polishing restorations. For in vitro studies, detrimental effects are possible when intra-pulpal temperature increases by more than 5.5°C (that is, the intra-pulpal temperature exceeds 42.4°C). This excessive heat transfer results in inflammation and necrosis of the pulp. Despite numerous studies stating the importance of heat transfer and control during dental procedures, there are limited studies that have quantified the significance. Past studies incorporated an experimental setup where a thermocouple is placed inside the pulp of an extracted human tooth and connected to an electronic digital thermometer. Methods: This review identified the opportunity for future research and develop both the understanding of various influencing factors on heat generation and the different sensor systems to measure the intrapulpal temperature. Conclusion: Various steps of dental restorative procedures have the potential to generate considerable amounts of heat which can permanently damage the pulp, leading to pulp necrosis, discoloration of the tooth and eventually tooth loss. Thus, measures should be undertaken to limit pulp irritation and injury during procedures. This review highlighted the gap for future research and a need for an experimental setup which can simulate pulp blood flow, temperature, intraoral temperature and intraoral humidity to accurately simulate the intraoral conditions and record temperature changes during various dental procedures. [ABSTRACT FROM AUTHOR]

Purpose: Soil heavy metal distribution is a key issue in environmental and health research. In recent years, an increasing number of anthropogenic disturbances have been identified on the Qinghai-Tibetan Plateau, leading to increased heavy metal contamination of soils. Therefore, this study investigated the distribution, sources, ecological risk, and prediction of heavy metals in soils on the Qinghai-Tibetan Plateau. Material and methods: Here, for each of the seven heavy metals (i.e., Cr, Ni, Cu, Zn, As, Cd, and Pb) investigated in the soil of the Qinghai-Tibet Plateau, we collected soil concentration values from the literature and carried out field sampling to generate new data. We then assessed the pollution characteristics and sources of soil heavy metals on the Qinghai-Tibet Plateau using geostatistics, positive matrix factorization model (PMF), disjunctive kriging, and mapped the pollution risk probability distribution of each heavy metal element. Results and discussion: Spatial autocorrelation was found for all seven heavy metals in the soils. Under different land-use types, the average concentrations of Cr, As, and Cd were highest in the water areas; Ni levels were highest in woodland; and Cu, Zn, and Pb concentrations were highest in residential, industrial, and mining lands. Using analysis by the PMF model and correlation analysis, four heavy metal sources were identified, including industrial sources and atmospheric deposition (Cd), traffic emissions (Cr, Zn, and Zn), natural sources (Ni and As), and mining activities (Cr and Pb). The pollution risk probabilities of Cr, Ni, Cu, Zn, As, and Pb were low in most areas of the Qinghai-Tibet Plateau, whereas the pollution risk probability of Cd was high over 29% of the area of the Qinghai-Tibet Plateau. Conclusion: The results highlighted no potential contamination for Cr, local potential contamination for Ni, Cu, Zn, As and Pb, while Cd exhibits more extensive contamination in the soils of the Qinghai-Tibet Plateau. Cd reduction should therefore be considered an important component of the strategy, policy, and action plan for soil pollution management on the Qinghai-Tibet Plateau. [ABSTRACT FROM AUTHOR]

The conversion of solid chitin into liquid low-molecular-weight polyol compounds using liquefaction technology can realize the high-value utilization of shrimp and crab shell marine waste. In this study, chitin liquefaction was conducted using sulfuric acid as the catalyst and propanetriol and polyethylene glycol as the liquefying agents. Thereafter, the acid number, hydroxyl value, viscosity and molecular weight of the chitin liquefaction product were tested and characterized. A polyurethane foam with low thermal conductivity and high mechanical strength was successfully synthesized. The preparation process was regulated by reacting the hydroxyl group that is abundant in chitin liquefaction with isocyanate instead of polyether polyol. Moreover, adding dimethyl methyl phosphate into the polyurethane to prepare flame retardant polyurethane foam. The flame retardance and thermal-insulation properties of the polyurethane foam synthesized using the chitin liquefaction product are significantly better than those of traditional polyol polyurethane foam, which broadens the application scope of polyurethane foam. [ABSTRACT FROM AUTHOR]

Bismuth (Bi) films were prepared using the molecular beam epitaxy (MBE) method and characterised using Raman spectroscopy, X-ray diffraction, ultraviolet-visible-near-infrared spectrophotometer, physical property measurement system and contact angle measurements. The experiment results demonstrated that Bi films with excellent transport characteristics were obtained via thickness adjustment. The Bi film exhibited excellent strong anisotropy at ~ 29 nm thickness. Meanwhile, the magnetoresistance (MR) was 20%, and the semimetal-semiconductor transition temperature was 54 K. The Bi film had satisfactory luminous transmittance, achieving a balance between light transmittance and electrical properties. Furthermore, the Bi film exhibits excellent hydrophobicity. This work suggests that Bi film become an excellent candidate for transparent conductive film materials and contact electrodes. [ABSTRACT FROM AUTHOR]

Infections induced by fungi, especially the drug-resistant fungi, are difficult clinical problems. Conventional antifungal treatment is effective but due to resistance, treatment failure, and treatment-related toxicity, there is a need for new antifungal drugs. In this study, SA-2 (YYRRLLRVLRRRW) was derived from Cystatin-SA, a saliva protein with a molecular weight of 14 kDa. Meanwhile, the structure–activity of SA-2 and its mutants was also studied. We detected the antimicrobial activity and cytotoxicity of SA-2 and found that SA-2 had a low cytotoxicity toward mammalian cells but a good inhibitory effect on Candida albicans (C. albicans) and Cryptococcus neoformans (C. neoformans), with MIC values of 16–64 μg/mL and 8–32 μg/mL, respectively. Interestingly, SA-2 effectively killed fluconazole-resistant C. neoformans and C. albicans within 12 h. This antifungal activity against fluconazole-resistant fungi was comparable to that of amphotericin B. In addition, the C. neoformans-infected mice model was established to evaluate the anti-infective activity of SA-2 in vivo. Results showed that SA-2 significantly reduced the counts of fungi in lung and brain tissues to protect fluconazole-resistant C. neoformans-infected mice from death without changing mice body weights. Moreover, the dramatically increased pro-inflammatory cytokines TNF-α, IL-6 and IL-1β induced by intranasal infection of C. neoformans could be obviously declined due to the treatment of SA-2, which may be attributed to the elimination of C. neoformans in time in the infected tissue. For the mode of actions underlying SA-2 against C. neoformans, we found that the cationic peptide SA-2 could adhere to the negatively charged fungal cell membrane to increase the surface potential of C. neoformans in a dose-dependent manner, and finally disrupted the integrity of fungal cell membrane, reflecting as a 60% positive rate of propidium iodide uptake of C. neoformans cells after SA-2 (4 × MIC) treatment. Our study indicated that SA-2 has the potential to develop as a new therapeutic agent against infection induced by drug-resistant fungi. [ABSTRACT FROM AUTHOR]

Ingestible robotic capsules with locomotion capabilities and on-board sampling mechanism have great potential for non-invasive diagnostic and interventional use in the gastrointestinal tract. Real-time tracking of capsule location and operational state is necessary for clinical application, yet remains a significant challenge. To this end, we propose an approach that can simultaneously determine the mechanism state and in-plane 2D pose of millimeter capsule robots in an anatomically representative environment using ultrasound imaging. Our work proposes an attention-based hierarchical deep learning approach and adapts the success of transfer learning towards solving the multi-task tracking problem with limited dataset. To train the neural networks, we generate a representative dataset of a robotic capsule within ex-vivo porcine stomachs. Experimental results show that the accuracy of capsule state classification is 97%, and the mean estimation errors for orientation and centroid position are 2.0 degrees and 0.24 mm (1.7% of the capsule's body length) on the hold-out test set. Accurate detection of the capsule while manipulated by an external magnet in a porcine stomach and colon is also demonstrated. The results suggest our proposed method has the potential for advancing the wireless capsule-based technologies by providing accurate detection of capsule robots in clinical scenarios. [ABSTRACT FROM AUTHOR]

Studies conducted at the beginning of this century revealed a warming and humidification trend in northwest China, which lasted for a short period, with some minor variations. The future trend remains uncertain, with uncertainty over the future duration of warming and humidification trends in the region. In this study, a comprehensive index was constructed to quantitatively characterize the degree of humidity. Using observation data, National Center for Atmospheric Research/National Centers for Environmental Prediction (NCAR/NCEP) reanalysis data, and future scenario prediction data we systematically analyzed the temporal and spatial evolution characteristics of the warming and humidification trend in northwest China and its possible causes. The results showed that the temperature in northwest China has been continuously increasing since 1961, and although there was no obvious precipitation trend from 1961 to 1999, it has been increasing nonlinearly since 2000. The wetness index considers the synergy of evaporation and precipitation, and had the same pattern of variation as precipitation. From a spatial perspective, the temperature has consistently increased throughout the whole northwest region, and the degree of warming has gradually increased. Precipitation displayed a trend of increasing in the west and decreasing in the east, but the area with increased rainfall expanded eastward over almost three climatic periods, and the area experiencing humidification extended across the whole of the northwest. There has been an obvious eastward expansion of climate humidification in northwest China since the start of this century. However, the current extent of climate humidification has not changed the basic climate pattern in northwest China. Over the next 30 years, the humidification trend will likely slow down significantly compared with the last 20 years. The eastward expansion of climate humidification since the start of this century may have resulted from the multi-decadal synergistic influence of westerly wind circulation and monsoon circulation. [ABSTRACT FROM AUTHOR]

It was theoretically predicted that electric field intensities generated by surface plasmon resonance (SPR) around plasmonic metallic nanostructures could be reduced after covered by wide bandgap semiconductor, thus worsening the SPR-mediated photocatalytic activities. However, we found that the Ag nanocubes (Ag NCs) covered by AgCl demonstrated an abnormal SPR-mediated catalytic enhancement. Herein the PATP-to-DMAB oxidization was used as a model reaction to explore the photocatalytic conversions. It was observed that the Ag NCs covered by AgCl ultra-thin layer (AgCl@Ag NCs) presented better photocatalytic activities than those of individual Ag NCs under 633-nm excitation. To reveal the mechanism behind the superior activities of AgCl@Ag NCs, the PATP-to-DMAB conversions were also carried out in ambient argon (Ar), in which AgCl@Ag NCs demonstrated significantly higher conversions. These results could be interpreted based on the separation of electron–hole pairs in AgCl through SPR effect of Ag, where the electrons in the valence band of AgCl were excited to the empty states of Ag, leaving holes in the semiconductor and resulting in the oxidation of PATP to DMAB. Thus, our findings may provide a novel way to enhance SPR-mediated photocatalytic activities on plasmonic metallic nanostructures by the cover of an ultra-thin layer of wide bandgap semiconductor. [ABSTRACT FROM AUTHOR]

Water-level fluctuations may affect the abundance and habitat distribution of waterbirds. We surveyed waterbirds in the Yangtze River in the Three Gorges Reservoir Region (TGRR) from January to early February annually from 2003 to 2013 (except 2011) and recorded the locations and numbers of individuals. Based on the survey results, we identified seven species, including the mallard (Anas platyrhynchos Linnaeus, 1758) and Chinese spot-billed duck (Anas zonorhyncha Swinhoe, 1866), in the core wintering waterbird community in the study area. We evaluated the community variation in richness and distribution and analyzed the relationships between the population and water level, temperature, humidity and precipitation. We recorded 23,556 waterbirds in our surveys; the total number of birds decreased slightly but not significantly during the study period. Among the seven species, a significant decreasing trend with increasing water level was observed only for the grey heron (Ardea cinerea Linnaeus, 1758) during the study period. The waterbirds were mainly observed upstream of Wanzhou county due to its shallow shores and meandering and rapid water in the TGRR. The correlations between the waterbird populations and annual average temperature and humidity were significant. Protected areas should be established in the shallows of upper Wanzhou county in the Yangtze River, and waterbird surveys should be strengthened throughout the TGRR. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infection is prevalent all over the world, which may even cause gastric cancer. Unfortunately, current antibiotic therapy cannot completely eradicate drug-resistant H. pylori. HF-18 (GFFKKAWRKVKKAFRRVL-NH2), a novel cationic antimicrobial peptide, showed broad antimicrobial activities, low cytotoxicity toward mammalian cells and low drug tolerance during our previous research. In this paper, to investigate the antibacterial activities and possible mechanisms underlying HF-18 against drug-resistant H. pylori, cytotoxin associated protein (CagA)-carrying recombinant E. coli BL21 was constructed. Subsequently, Zeta potential detection, N-Phenyl-1-naphthylamine uptake, propidium iodide fluorescence uptake, transmission electron microscope, qRT-PCR and Western blot assays were performed. Consequently, we found that HF-18 had potent antibacterial effects on clarithromycin- and amoxicillin- resistant H. pylori. In terms of its mode of action, HF-18 could neutralize negative charges on the surface of H. pylori, penetrate into and disrupt the integrity of bacterial membranes, resulting in the death of drug-resistant H. pylori to reduce cells infection. In addition, HF-18 inhibited the transcription of adhesion gene alpA/alpB and the expression of virulence protein CagA under sub-inhibitory concentration, and ultimately decreased bacterial virulence. Therefore, HF-18 lays a foundation for the development and utilization of new antibiotics. [ABSTRACT FROM AUTHOR]

Purpose: Alcoholic liver disease (ALD) is a major health issue globally. In addition to pharmacotherapy, dietary support is also regarded as reliable strategy for ALD management. As a widely distributed natural constituent within edible plants, the present study aims to investigate the hepatoprotective effects of ursolic acid (UA) against ALD and also to deepen insights into the underlying targets and mechanisms comprehensively. Methods: The hepatoprotective activity of UA against chronic alcohol-induced liver injury was investigated on Lieber–DeCarli liquid diet-based mouse model. In-depth RNA-seq transcriptomics and TMT-based proteomics analyses were conducted in parallel. Data integration as well as bioinformatics analysis were also performed to unravel the targets and mechanisms associated with the hepatoprotective activity of UA intake against alcoholic liver injury comprehensively. Results: The serum biomarkers and pathological characteristics indicated the hepatoprotective effects of UA intake on alcoholic liver injury. 567 target genes and 377 target proteins related to the hepatoprotective activity of UA were identified in transcriptomics and proteomics analysis respectively, most of which were associated with function of cellular process, cell part and binding. After data integration, 56 co-regulated targets, including ADH4, CYP450 enzymes, NQO1, apolipoproteins, glutathione–S–transferase, etc. which were consistently modulated on both mRNA and protein levels were identified. These co-regulated targets were found to be correlated with 70 KEGG pathways led by carcinogenesis, retinol metabolism and CYP450 metabolism pathways. Conclusion: UA intake ameliorated chronic alcohol-induced liver injury. Given the role of the co-regulated targets in ALD and the bioinformatics analysis results, CYP450-, glutathione and redox homeostasis-dependent antioxidation, promotion of lipid transport, and restoration of ethanol metabolic capacity are the potentially underlying mechanisms. This information will further deepen our insights into the hepatoprotective effects of UA-rich edible plants, and provide us valuable instruction for ALD management. [ABSTRACT FROM AUTHOR]

The poor stability of peptides against trypsin largely limits their development as potential antibacterial agents. Here, to obtain a peptide with increased trypsin stability and potent antibacterial activity, TICbf-14 derived from the cationic peptide Cbf-14 was designed by the addition of disulfide-bridged hendecapeptide (CWTKSIPPKPC) loop. Subsequently, the trypsin stability and antimicrobial and antibiofilm activities of this peptide were evaluated. The possible mechanisms underlying its mode of action were also clarified. The results showed that TICbf-14 exhibited elevated trypsin inhibitory activity and effectively mitigated lung histopathological damage in bacteria-infected mice by reducing the bacterial counts, further inhibiting the systemic dissemination of bacteria and host inflammation. Additionally, TICbf-14 significantly repressed bacterial swimming motility and notably inhibited biofilm formation. Considering the mode of action, we observed that TICbf-14 exhibited a potent membrane-disruptive mechanism, which was attributable to its destructive effect on ionic bridges between divalent cations and LPS of the bacterial membrane. Overall, TICbf-14, a bifunctional peptide with both antimicrobial and trypsin inhibitory activity, is highly likely to become an ideal candidate for drug development against bacteria. [ABSTRACT FROM AUTHOR]

Mouse caspase-11 and human caspase-4 and caspase-5 recognize cytosolic lipopolysaccharide (LPS) to induce pyroptosis by cleaving the pore-forming protein GSDMD1–5. This non-canonical inflammasome defends against Gram-negative bacteria6,7. Shigella flexneri, which causes bacillary dysentery, lives freely within the host cytosol where these caspases reside. However, the role of caspase-11-mediated pyroptosis in S. flexneri infection is unknown. Here we show that caspase-11 did not protect mice from S. flexneri infection, in contrast to infection with another cytosolic bacterium, Burkholderia thailandensis8. S. flexneri evaded pyroptosis mediated by caspase-11 or caspase 4 (hereafter referred to as caspase-11/4) using a type III secretion system (T3SS) effector, OspC3. OspC3, but not its paralogues OspC1 and 2, covalently modified caspase-11/4; although it used the NAD+ donor, this modification was not ADP-ribosylation. Biochemical dissections uncovered an ADP-riboxanation modification on Arg314 and Arg310 in caspase-4 and caspase-11, respectively. The enzymatic activity was shared by OspC1 and 2, whose ankyrin-repeat domains, unlike that of OspC3, could not recognize caspase-11/4. ADP-riboxanation of the arginine blocked autoprocessing of caspase-4/11 as well as their recognition and cleavage of GSDMD. ADP-riboxanation of caspase-11 paralysed pyroptosis-mediated defence in Shigella-infected mice and mutation of ospC3 stimulated caspase-11- and GSDMD-dependent anti-Shigella humoral immunity, generating a vaccine-like protective effect. Our study establishes ADP-riboxanation of arginine as a bacterial virulence mechanism that prevents LPS-induced pyroptosis.This study reports the identification of a new post-translational modification, termed ADP riboxanation, which is mediated by the Shigella effector OspC3 and inactivates the cytosolic LPS sensing pathway of caspase-4 and caspase-11. [ABSTRACT FROM AUTHOR]

Evolutionarily, polyploidy represents a smart method for adjusting agronomically important in crops through impacts on genomic abundance and chromatin condensation. Autopolyploids have a relatively concise genetic background with great diversity and provide an ideal system to understand genetic and epigenetic mechanisms attributed to the genome-dosage effect. However, whether and how genome duplication events during autopolyploidization impact chromatin signatures are less understood in crops. To address it, we generated an autotetraploid rice line from a diploid progenitor, Oryza sativa ssp. indica 93-11. Using transposase-accessible chromatin sequencing, we found that autopolyploids lead to a higher number of accessible chromatin regions (ACRs) in euchromatin, most of which encode protein-coding genes. As expected, the profiling of ACR densities supported that the effect of ACRs on transcriptional gene activities relies on their positions in the rice genome, regardless of genome doubling. However, we noticed that genome duplication favors genic ACRs as the main drivers of transcriptional changes. In addition, we probed intricate crosstalk among various kinds of epigenetic marks and expression patterns of ACR-associated gene expression in both diploid and autotetraploid rice plants by integrating multiple-omics analyses, including chromatin immunoprecipitation sequencing and RNA-seq. Our data suggested that the combination of H3K36me2 and H3K36me3 may be associated with dynamic perturbation of ACRs introduced by autopolyploidization. As a consequence, we found that numerous metabolites were stimulated by genome doubling. Collectively, our findings suggest that autotetraploids reshape rice morphology and products by modulating chromatin signatures and transcriptional profiling, resulting in a pragmatic means of crop genetic improvement. [ABSTRACT FROM AUTHOR]

Hexachlorobutadiene (HCBD) was classed as a persistent organic pollutant under the Stockholm Convention in 2015. HCBD is mainly an unintentionally produced by-product of chlorinated hydrocarbon (e.g., trichloroethylene and tetrachloroethylene) synthesis. Few studies of HCBD formation during chemical production processes have been performed, so HCBD emissions from these potentially important sources are not understood. In this study, HCBD concentrations in raw materials, intermediate products, products, and bottom residues from chemical plants producing chlorobenzene, trichloroethylene, and tetrachloroethylene were determined. The results indicated that HCBD is unintentionally produced at much higher concentrations in trichloroethylene and tetrachloroethylene plants than chlorobenzene plants. The sum of the HCBD concentrations in the samples from all of the trichloroethylene and tetrachloroethylene production stages in plant PC was 247000 µg/mL, about three orders of magnitude higher than the concentrations in the tetrachloroethylene production samples (plant PB) and about six orders of magnitude higher than the concentrations in the chlorobenzene production samples (plant PA). The HCBD concentrations were highest in bottom residues from all of the plants. The concentrations in the bottom residue samples contributed 24%–99% of the total HCBD formed in the chemical production plants. The bottom residue, being hazardous waste, could be disposed of by incineration. The HCBD concentrations were much higher in intermediate products than raw materials, indicating that HCBD formed during production of the intended chemicals. The results indicate the concentrations of HCBD unintentionally produced in typical chemical plants and will be useful in developing protocols for controlling HCBD emissions to meet the Stockholm Convention requirements. [ABSTRACT FROM AUTHOR]

This study aimed to examine the cerebral cortex characteristics (thickness, surface area, and curvature) in patients with major depressive disorder (MDD), and explore whether these cortex characteristics are predictors for the antidepressant therapeutic effect. 105 patients with MDD and 49 healthy controls (HCs) were recruited. Both groups were given magnetic resonance image (MRI) scans at baseline period, and then the cerebral cortex characteristics (thickness, surface area, and curvature) were calculated using the DPABISurf software. The Hamilton Depression Scale-24 (HAMD-24) reductive rate was used to measure antidepressant therapeutic effect and Snaith Hamilton Rating Scale (SHAPS) reduction was performed to assess the change of anhedonia after treatment of 8 weeks. Correlation analysis was performed to identify the relationship between cortex characteristics and antidepressant therapeutic effect in patients with MDD. There were no significant differences in the cortical curvature and surface area between MDD and HC groups, while significant decreases were found in the cortical thickness of inferior frontal cortex (IFC), premotor cortex (PMC), orbital and medial prefrontal cortex (OMPFC) in the left hemisphere of MDD group, comparing with HC group (P < 0.05 for all, corrected by threshold-free cluster enhancement). In MDD group, the cortical thickness of left PMC had significant positive correlations with 8-week HAMD-24 reduction (r = 0.228, P = 0.020) and HAMD-24 reductive rate (r = 0.193, P = 0.048); and a negative correlation with the 8-week SHAPS reduction (r = -0.240, P = 0.018). Decreased cortical thickness in left PMC may be a predictor of therapeutic effect in MDD. Determining the cortical thickness of this region before treatment can provide certain reference value for clinical antidepressant treatment. [ABSTRACT FROM AUTHOR]

The East Asia summer monsoon transition zone, a unique area of transition from humid monsoon to arid continental climate, has the most prominent aridification in the world, and has experienced land surface aridification (LSA) in recent years. To investigate the influence of LSA on regional monsoon precipitation, two numerical experiments were run for vegetation degradation over a long period (30 years). Then, precipitation variation of different magnitudes was analyzed. After that, the mechanism of LSA influence on precipitation was studied. The results show that aridification reduced average summer precipitation by 5%. Additionally, LSA considerably changed the frequency of precipitation. Unlike aridification in North Africa caused by albedo variation, LSA in our study area mainly reduced surface thermal capacity, increased surface temperature, sharply increased the transport of surface sensible heat, and raised the atmospheric convective boundary layer. This reduces atmospheric moist static energy, which is not conducive to the generation of precipitation. LSA also increases the surface landscape gradient, local horizontal gradient of land surface turbulent flux, and probability of heavy convective precipitation. This paper reveals the mechanism by which land surface anomalies affect precipitation, which lays a foundation for follow-up studies. [ABSTRACT FROM AUTHOR]

Nanocomposites with great thermal stability and excellent dielectric properties play a vital role in the development of high-temperature resistant capacitors. A facile yet effective method to synthesize enhanced dielectric properties of thermostable three-phase poly(p-phenylene benzobisoxazole) (mCCTO@CFGO/PBO) nanocomposite films is demonstrated in this work. The amino-functionalized oxide CaCu3Ti4O12 nanoparticles (mCCTO) are enwrapped by the carboxyl-functionalized ultrathin graphene shells (CFGO), forming the silk-cocoon structure to achieve homogeneous dispersion in the matrix. The final films are fabricated via in situ polymerization by introducing the mCCTO@CFGO nanoparticles into the PBO precursor polymer. The mCCTO@CFGO/PBO nanocomposite films exhibit high thermal stability (the 5% thermal decomposition temperature is 655 °C), while the unique silk-cocoon structure effectively confers the high dielectric constant up to 86.9 and ultra-low dielectric loss (0.063) with the loading of 10 wt% mCCTO@3 wt% CFGO/PBO at 1 kHz and 200 °C. This promising strategy accelerates the development of electronic devices used under high temperatures. [ABSTRACT FROM AUTHOR]

SDG711 is a histone H3K27me2/3 transmethylase in rice, a homolog of CLF in Arabidopsis, and plays key roles in regulating flowering time and panicle development. In this work, we investigated the role of SDG711 in rice seed development. Overexpression and downregulation of SDG711 lead to a decrease and increase in the expression level of genes related to starch accumulation, resulting in smaller seeds or even seed abortion. ChIP assay showed that SDG711-mediated H3K27me3 changed significantly in genes related to endosperm development, and SDG711 can directly bind to the gene body region of several starch synthesis genes and amylase genes. In addition, H3K4me3 and H3K9ac modifications also cooperate with H3K27me3 to regulate the development of the endosperm. Our results suggest that the crosstalk between SDG711-mediated H3K27me3 and H3K4me3, and H3K9ac are involved in starch accumulation to control normal seed development. [ABSTRACT FROM AUTHOR]

The climatic warming and humidification observed in the arid region of Northwest China (ARNC) and their impacts on the ecological environment have become an issue of concern. The associated multi-scale characteristics and environmental responses are currently poorly understood. Using data from satellite remote sensing, field observations, and the Coupled Model Intercomparison Project phase 6, this paper systematically analyzes the process and scale characteristics of the climatic warming and humidification in the ARNC and their impacts on ecological vegetation. The results show that not only have temperature and precipitation increased significantly in the ARNC over the past 60 years, but the increasing trend of precipitation is also obviously intensifying. The dryness index, which comprehensively considers the effects of precipitation and temperature, has clearly decreased, and the trend in humidification has increased. Spatially, the trend of temperature increase has occurred over the entire region, while 93.4% of the region has experienced an increase in precipitation, suggesting a spatially consistent climatic warming and humidification throughout the ARNC. Long-term trends and interannual changes in temperature and precipitation dominate the changes in climatic warming and humidification. Compared to interannual variations in temperature, the trend change of temperature contributes more to the overall temperature change. However, the contribution of interannual variations in precipitation is greater than that of the precipitation trend to the overall precipitation change. The current climatic warming and humidification generally promote the growth of ecological vegetation. Since the 1980s, 82.4% of the regional vegetation has thrived. The vegetation index has a significant positive correlation with precipitation and temperature. However, it responds more significantly to interannual precipitation variation, although the vegetation response varies significantly under different types of land use. The warming and humidification of the climate in the ARNC are probably related to intensifications of the westerly wind circulation and ascending air motions. They are expected to continue in the future, although the strength of the changes will probably be insufficient to significantly change the basic climate pattern in the ARNC. The results of this study provide helpful information for decision making related to China's "Belt and Road" development strategies. [ABSTRACT FROM AUTHOR]

Background: The incidence of thyroid cancer (TC) is increasing rapidly worldwide. The target therapy for papillary TC (PTC) is limited, and the studies of PTC prognostic biomarkers are not common. As a new member of annexin A (ANXA) family, the function and clinical significance of ANXA10 in PTC have not been well investigated. Methods: Expressions of all the 12 ANXA members were detected with qPCR in 12 PTC tissues, and the ANXA10 mRNAs in PTCs and their adjacent normal thyroid tissues were compared. The subcellular location and expression of ANXA10 in 121 PTC patients were investigated with immunohistochemistry, which further classified the patients into subgroups with low or high ANXA10. The clinical significance and prognostic value of ANXA10 were estimated by analyzing its correlation with clinical factors and overall survival rates by the chi-squared test, univariate analyses, and multivariate analyses. Results: ANXA10 had the highest expression in PTCs among all the ANXA members. Moreover, ANXA10 was significantly upregulated in PTC compared with normal thyroid tissues. The PTC patients with low and high expression of ANXA10 took up 70.25% (85/121) and 29.75% (36/121), respectively. ANXA10 expression was associated with tumor size, differentiation, and overall survival rates of PTC. ANXA10 was an independent prognostic biomarker predicting the poor outcome of PTC. Conclusions: ANXA10 expression was upregulated in PTC, and it was an independent prognostic biomarker of PTC, suggesting that ANXA10 may be a promising target for individual treatment of ANXA10. [ABSTRACT FROM AUTHOR]

Background: Cholinesterase as a sensitive biomarker for prognosis in a variety of conditions but it is rare in stroke studies. The very elderly (≥ 80 years of age) represent the most susceptible group of ischemic stroke. We aimed to determine whether admission serum cholinesterase concentration had any effect on clinical outcome in very elderly patients (individuals aged ≥ 80 years) with acute ischemic stroke. Methods: A retrospective record review was conducted in two tertiary university hospitals. Elderly patients aged ≥ 80 years admitted with a diagnosis of acute ischemic stroke from January 1, 2014 to November 30, 2019, who had a cholinesterase concentration drawn, were included. The patients were grouped based on the inflection points of the locally weighted regression and smoothing scatterplot (LOESS) curve between cholinesterase levels and in-hospital mortality (study outcome) with lower concentration as reference group. Results: A total of 612 patients were admitted with a diagnosis of acute ischemic stroke, and 569 met the inclusion criteria. A threshold effect was identified using regression smoothing scatterplot (LOESS), with one cutoff point of 4.0 KU/L. There was a significant difference in-hospital mortality was observed (P < 0.001). After adjusted demographic and clinical features, the OR of cholinesterase for mortality was 0.43 (95% CI 0.34–0.54, P < 0.001), suggesting that lower admission cholinesterase level was an independent risk factors for all-cause mortality among patients with AIS. Conclusions: We have demonstrated a significant association between admission cholinesterase concentration and in-hospital mortality in very elderly patients with AIS. [ABSTRACT FROM AUTHOR]

Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. The dorsolateral striatum (DLS) is part of corticostriatal circuits that is involved in flexible behavior. Pro-brain-derived neurotrophic factor (proBDNF) can enhance fear memory extinction and weaken synaptic transmission, which may enable flexible adaptations. However, the role of proBDNF in cognitive flexibility is unclear. Here, through infusion of cleavage-resistant proBDNF or its antibody into the DLS of rats, we sought evidence for the influences by employing behavioral tests, immunoblotting, immunocytochemistry, and electrophysiological recoding. Infusion of proBDNF significantly facilitated reversal learning while inhibiting DLS proBDNF by anti-proBDNF antibody impaired the behavioral performance. Furthermore, elevation of DLS proBDNF facilitated neural correlate with reversal performance while blocking proBDNF expression decayed the spike-field coupling during the correct turning. Reversal learning induced increases in endogenous neuronal proBDNF, with a strong correlation between DLS and infralimbic cortex (IL), but not prelimbic cortex (PL) or sensory-motor cortex (SM). Importantly, blockade of IL proBDNF disrupted the DLS-mediated reversal learning enhancement, implying the involvement of both IL and DLS regions in reversal habitual behavior. Taken together, our findings provide first evidence for the essential role of the DLS proBDNF in cognitive flexibility and suggest that proBDNF-mediated neural function could be the mechanism. [ABSTRACT FROM AUTHOR]

Purpose: The different mechanisms that trigger the autoimmune attack to the thyroid between Hashimoto's thyroiditis (HT) and Graves' disease (GD) are still unclear. The aim of this study was to recognize thyroid antigens specific CD8+ T-cell epitopes and explore the relationship between these epitopes and thyroid autoantibodies, duration and classification in these two diseases. Methods: Free thiiodothyronine, free tetraiodothyronine, thyroid-stimulating hormone, TgAb, and TPOAb were all measured by immunochemiluminometric assays, while TRAb was tested by radioimmunoassay. HLA class I peptide affinity algorithms were applied to predict candidate thyroid autoantigen peptides that blind to HLA-A*0201. The ELISpot assay was used to detect Tg-, TPO-, and TSHR-specific CD8+ T cells. Results: We demonstrated that TG-6 was a novel HLA-A*0201-restricted CTL epitope in GD. TG-6, TG-7, TG-10, TG-11, and TPO-6 were immunodominant in GD patients compared with HT patients (TG-6: 38.5 vs. 8%, P = 0.034; TG-7, TG-10, TG-11, and TPO-6: 23.1 vs. 0%, P = 0.034). The immunodominance of TG-6 in GD patients was more evident than healthy controls (HC) (TG-6: 35.8 vs. 0%, P = 0.011), but there was no statistically significant difference between HT patients and HC. Subgroup analyses revealed the T-cell responsiveness to TG-6 was stronger in TgAb-negative HT patients (0 vs. 40%, P = 0.033). However, there was no correlation showed for TPOAb, TRAb, medication and duration in both HT and GD patients. Conclusions: We report for the first time that both diseases, HT and GD, recognize different antigen-specific CD8-positive T cells. Tg maybe the dominant thyroid autoantigen contributing to breaking tolerance in GD. It could improve our knowledge of autoimmune thyroid diseases pathogenesis as well as offer new therapeutical tools in terms of peptide vaccine therapy. [ABSTRACT FROM AUTHOR]

Chemical profile and antioxidant potency of essential oils (EOs) of Thymus quinquecostatus Celak. (thyme oils) obtained from Loess Plateau in China had been studied. 130 constituents of thyme oils were determined using gas chromatography-mass spectrometry (GC–MS) and carvacrol ethyl ether was firstly reported as a new natural product, which has been used as a synthetic flavoring substance with no safety concern. The thyme oils showed the anti-oxidant activity using 2,2 diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) and conferred protection against oxidative stress in zebrafish. In addition, a class of carvacrol analogues was found to develop as potential natural antioxidant products of thyme oils from Loess Plateau by the correlation analysis. YL-thyme oil performed the best antioxidant activity in this research, which could be recommended as preferred sources of thyme oils. Furthermore, YL-thyme oil exhibited a potent antioxidant capacity by reactive oxygen species (ROS) scavenging, enhancing the endogenous antioxidant system, inhibiting lipid peroxidation and activation of Keap1/Nrf2 pathway in zebrafish. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Typhimurium, an intracellular Gram-negative bacterial pathogen, employs two type III secretion systems to deliver virulence effector proteins to host cells. One such effector, SseK3, is a Golgi-targeting arginine GlcNAc transferase. Here, we show that SseK3 colocalizes with cis-Golgi via lipid binding. Arg-GlcNAc-omics profiling reveals that SseK3 modifies Rab1 and some phylogenetically related Rab GTPases. These modifications are dependent on C-termini of Rabs but independent of the GTP- or GDP-bound forms. Arginine GlcNAcylation occurs in the switch II region and the third α-helix and severely disturbs the function of Rab1. The arginine GlcNAc transferase activity of SseK3 is required for the replication of Salmonella in RAW264.7 macrophages and bacterial virulence in the mouse model of Salmonella infection. Therefore, this SseK3 mechanism of action represents a new understanding of the strategy adopted by Salmonella to target host trafficking systems. Meng, Zhuang, Peng et al. study the role of a Golgi-targeting arginine GlcNAc transferase, SseK3, in the pathogenesis of Salmonella enterica. Through R-GlcNAcylated proteome analysis, they identify Rab proteins as targets for SseK3 as well as their modification sites. They demonstrate that SseK3 GlcNAc transferase activity is required for bacterial virulence in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The deformation and failure of composite rock masses at the contact zone can cause serious safety hazards in underground engineering. Therefore, uniaxial compression experiment and numerical studies of composite samples were conducted. Combined with theoretical analysis, the effects of differences in the mechanical properties of two media on the mechanical properties and failure form of composite samples were investigated. The results show that the difference in mechanical properties of two media weakened the strength and elastic modulus of the composite sample and resulted in complex failure form of the sample. Additionally, the peaks of the AE frequencies of the two media occurred successively after the peak stress of the sample. At the macrolevel, the two media failed successively. These effects are more pronounced as the degree of difference in the mechanical properties of the two media increased. The difference in mechanical properties of the two media resulted in uncoordinated deformation and constrained stress near the contact interface, and the difference in Poisson's ratio is the main factor. The influence (enhanced or weakened) of uncoordinated deformation on the mechanical properties of the composite sample is affected by differences in the elastic modulus and Poisson's ratios of the two media. [ABSTRACT FROM AUTHOR]

The Corresponding Author has stated that ethics approval was obtained, but the number was not included in the article by mistake. In addition, the authors have not provided the ethics approval number and consent statement in the article, and the patients are not well described. [Extracted from the article]

In this study, a Gram-negative, rod-shaped, and non-spore-forming bacterium, which was designated as strain CCBUA 65841T, was isolated from a root nodule of Calopogonium mucunoides grown in Yunan Province of China. The sequence alignment results of 16S rRNA and four housekeeping genes (including gyrB, recA, dnaK and rpoB) indicated the isolated strain is a member of the genus Microvirga, closely related to Microvirga lotononidis WSM3557T. In addition, results of genome average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) had revealed the lower values (ANI ≤ 88.72%, dDDH ≤ 39.5%) between strain CCABU 65841T and other related Microvirga species. The genome of the novel strain exhibits a G + C content of 64.48% and contains 7296 protein-coding genes and 93 RNA genes. The major polar lipids were found to be phosphatidylcholine and phosphatidylethanolamine. The predominant cellar fatty acids were identified to be C16:0, C18:0, C19:0 cyclo ω8c, summed feature 2, summed feature 3 and summed feature 8. Moreover, menaquinone 8 (MK-8) was detected to be the predominant quinone. Based on the phylogenetic and phenotypic dissimilarity, a novel species Microvirga calopogonii sp. nov. is proposed with the type strain CCABU 65841T (= LMG 25488 T = HAMBI 3033T). [ABSTRACT FROM AUTHOR]

To explore the mechanism of transcranial direct current stimulation (tDCS) on the improved performance of professional rowing athletes. Twelve male professional rowing athletes were randomly divided into two groups (low-stimulation group, 1 mA, n = 6; high-stimulation group, 2 mA, n = 6), and they accepted tDCS for two consecutive weeks while undergoing regular training (20 min each time, five times a week, totally ten times). The assessments of depression, anxiety, executive function, fatigue perception, lactate threshold power (LTP) and isokinetic muscle strength as well as the collection of functional magnetic resonance imaging (fMRI) data were performed at baseline and at follow-up (the end of the fourth week). The voxel-mirrored homotopic connectivity (VMHC) value was calculated in the whole brain. After stimulation, there were significant increases in executive function and athletic performance. Analysis of variance (ANOVA) analysis indicated time factor, stimulation intensity factor had a main effect on LTP and 60RK, respectively. There was no significant difference of VMHC value between the high- and low-stimulation groups at baseline. Comparing with low-stimulation group, significant increased VMHC values of the bilateral middle temporal gyrus (MTG), precentral gyrus and superior frontal gyrus (SFG) were found in high-stimulation group at follow-up. Correlation analyses showed that in high-stimulation group, the VMHC values of bilateral MTG and SFG were both positively correlated with the measures of athletic performance. tDCS may contribute to the improvement of athletic performance in professional rowing athletes, and the increased interhemispheric coordination may be involved in the mechanism of the improved athletic performance. [ABSTRACT FROM AUTHOR]

Candicidin is one of the frequent antibiotics for its high antifungal activity, but the productivity is still extremely low. Introduction of adpA into Streptomyces ZYJ-6 could improve candicidin productivity significantly and achieved 9338 μg/mL, which was the highest value ever reported in the literature. Combined analyses of transcriptional levels, metabolic flux and metabolomics indicate that para-aminobenzoic acid and the first step of shikimic acid metabolism were not the bottleneck for the candicidin production in the control. However, methylmalonyl-CoA played a central role in the candicidin production and the gene methB responsible for the biosynthesis of methylmalonyl-CoA might be the candidate gene target for further improving the production of candicidin. [ABSTRACT FROM AUTHOR]

Candicidin is one of the most effective antimonilial agents. In order to enhance candicidin productivity, medium optimization and pH stepwise control strategy in process optimization were conducted by Streptomyces ZYJ-6. With the aid of Design Expert software and N/C/P-sources regulation, chemically defined medium fit for cell growth and candicidin biosynthesis was developed. Moreover, pH effects on cell growth and metabolism were investigated. The results indicated that the optimal pH for cell growth and candicidin biosynthesis were 6.8 and 7.8, respectively. The metabolomics analysis revealed that the pH stepwise control strategy (pH 6.8-7.8) combined the advantages of pH 6.8 and pH 7.8 and avoided precursor limitation in pH 6.8 and 7.8. Consequently, the pH stepwise control strategy played positive performance on cell growth and candicidin biosynthesis with the maximum titer of 5161 µg/mL. The titer of 5161 µg/mL was the highest level ever reported for candicidin production, which laid a solid foundation for industrial application. Additionally, pH stepwise control strategy was important reference for process optimization. [ABSTRACT FROM AUTHOR]

The high-throughput, cost-efficient transformation systems determine the success of gene cloning and functional analysis. Among various factors that affect this transformation systems, the competence ability of target cells is one of the most important factors. We found antimicrobial peptides LFcin-B can increase the permeability of the cell membrane, and their lethal antibacterial properties can be inhibited by moderately high concentrations of Ca2+ and Mn2+. In this study, we established a convenient and rapid method (CRM) by adding small concentrations of (0.35 mg/L) and moderately high concentrations of MnCl2 (50 mM) and CaCl2 (30 mM) in transformation buffer. The transformation efficiency of E. coli cells (DH5α, JM109 and TOP10) prepared by CRM were comparable with electroporation for plasmid transformation (3.1 ± 0.3 × 109 cfu/µg). Unlike competent cells prepared using other chemical methods, those obtained using CRM method are extremely competent for receiving larger size DNA fragments (> 5000 bp) into plasmid vectors. The competent E. coli cells prepared by CRM method are particularly useful for most high-efficiency transformation experiments under normal laboratory conditions. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to explore some novel diagnostic biomarkers for papillary thyroid carcinoma (PTC) by identifying the different expression of TROP-2, SLP-2 and CD56 in benign and malignant thyroid lesions.Methods: We evaluated the mRNA expressions of TROP-2 and SLP-2 in fine needle aspirates (FNAs) which contained 10 PTCs and 10 benign follicular adenomas (FAs) using quantitative real-time PCR (qRT-PCR). Immunohistochemical (IHC) staining of TROP-2, SLP-2 and CD56 was also performed on postoperative samples of 30 PTCs and 29 FAs. Membranous or cytoplasmic staining in > 10% of cells was considered as positive. Diagnostic sensitivity, specificity, positive predictive value, negative predictive value (NPV) and diagnostic accuracy of these three biomarkers were carried out. We further analyzed the associations between the clinical features and the expressions of markers in PTCs.Results: The mRNA expressions of both TROP-2 and SLP-2 were increased substantially in PTCs in comparison with those in FAs (P < 0.05). Similarly, IHC for these two proteins demonstrated higher positive staining in PTCs than in FAs (96.5% vs. 12.5% for TROP-2, 83.3% vs. 20.7% for SLP-2, P < 0.05). Conversely, CD56 expression was lost with 86.7% of PTCs. In identifying malignancy, TROP-2 was the most sensitive marker and CD56 was the most specific one. When the markers were combined, the sensitivity and NPV increased to 100% and had better diagnostic accuracy. However, no association was found between biomarker expressions and clinicopathological factors in PTCs.Conclusions: We found that TROP-2, SLP-2 and CD56 were effective diagnostic markers for PTC, especially when they were combined to use. [ABSTRACT FROM AUTHOR]