[Study on fatigue resistance of mechanical nickel-titanium files by phase-locked infrared flaw detection method].

PURPOSE: The fatigue resistance of mechanical nickel-titanium files was tested by phase-locked infrared flaw detection method, in order to timely detect instrument wear, providing reference for clinical safe use and timely abandonment of nickel-titanium files. METHODS: Twenty sets of mechanical nickel-titanium files were selected from Reciproc-Blue(RB), MTWO and S3 respectively, and resin simulated root canals with 60° and 90° bending were prepared, which were divided into 6 subgroups. The fatigue value after use, the number of uses before breaking and the length of fracture of file 25# of each group of files were recorded and compared with SPSS 26.0 software package. RESULTS: With the increase of the times of use, the fatigue value of the three kinds of files increased gradually. Among the two types of curved root canals, the number of uses before fracture in RB group was significantly increased compared with that in MTWO group and S3 group (P＜0.05). The number of uses of the three kinds of files in the 90° curved root canal were significantly less than in the corresponding groups in the 60° curved root canal(P＜0.05). There was no significant difference in the length of fracture among the three kinds of files(P＞0.05). CONCLUSIONS: Phase-locked infrared flaw detection method can be used for non-destructive testing and quantitative analysis of the fatigue degree of nickel-titanium files.

Disruption of glucose homeostasis by bacterial infection orchestrates host innate immunity through NAD+/NADH balance.

Metabolic reprogramming is crucial for activating innate immunity in macrophages, and the accumulation of immunometabolites is essential for effective defense against infection. The NAD+/NADH (ratio of nicotinamide adenine dinucleotide and its reduced counterpart) redox couple serves as a critical node that integrates metabolic pathways and signaling events, but how this metabolite couple engages macrophage activation remains unclear. Here, we show that the NAD+/NADH ratio serves as a molecular signal that regulates proinflammatory responses and type I interferon (IFN) responses divergently. Salmonella Typhimurium infection leads to a decreased NAD+/NADH ratio by inducing the accumulation of NADH. Further investigation shows that an increased NAD+/NADH ratio correlates with attenuated proinflammatory responses and enhanced type I IFN responses. Conversely, a decreased NAD+/NADH ratio is linked to intensified proinflammatory responses and restrained type I IFN responses. These results show that the NAD+/NADH ratio is an essential cell-intrinsic factor that orchestrates innate immunity, which enhances our understanding of how metabolites fine-tune innate immunity.

Endodontic microsurgery and prosthodontic treatment of a permanent anterior concrescence: A case report.

Concrescence is a rare dental anomaly in which two adjacent teeth are united only by their cementum. Concrescence most frequently occurs in molars, especially a third mandibular molar and a supernumerary tooth. It is rarely seen in the maxillary anterior teeth. This case report is the first in the literature which details the successful treatment of a concrescence between the maxillary central incisor and a supernumerary tooth through multidisciplinary therapy. The treatment plan included root canal treatment, endodontic microsurgery, and prosthodontic treatment.

A phosphodiesterase CpdB in Yersinia pseudotuberculosis degrades CDNs to inhibit innate immune response.

Yersinia pseudotuberculosis (Yptb) is a pathogenic gram-negative bacterium that can colonize the intestines of different animals. Its infection leads to the activation of the host's innate immunity. Both host and bacterial-derived cyclic dinucleotides (CDNs) could activate the innate immune response of host cells. In bacteria, CDNs like c-di-AMP, c-di-GMP, or 3'3'-cGAMP can be hydrolyzed by different hydrolases. Recent studies showed that the degradation of those second messengers helps the pathogen evade immune detection. In this study, we identified a hydrolase, YPK_3776, namely CpdB in Yptb. CpdB is predicted to bind bacterial-derived c-di-AMP, c-di-GMP, 3'3'-cGAMP and host-derived 2'3'-cGAMP. Surprisingly, by using high-performance liquid chromatography (HPLC), we found that CpdB could only degrade bacterial-derived CDNs but not host-derived 2'3'-cGAMP. In addition, CpdB has 2'3'-cNMP activity. Consistently, the Yptb mutant lacking the cpdB gene exhibited a higher level of intracellular c-di-GMP. Furthermore, the ∆cpdB mutant elicited stronger innate immune responses during Yptb infection in macrophages, suggesting CpdB enables Yptb to evade host immune surveillance. Furthermore, CpdB inhibited the Yptb-induced innate immune response in a STING-dependent manner. Finally, we showed the ∆cpdB infection in mice model exhibited in lower bacterial burden, as compared to wild-type strain infection, indicating CpdB is important for bacterial survival in the host. Together, we identified a cyclic dinucleotide hydrolase CpdB in Yptb that could degrade bacterial-derived CDNs which help the pathogen to evade immune detection via the STING pathway.

Motion-Aware Video Frame Interpolation.

Video frame interpolation methodologies endeavor to create novel frames betwixt extant ones, with the intent of augmenting the video's frame frequency. However, current methods are prone to image blurring and spurious artifacts in challenging scenarios involving occlusions and discontinuous motion. Moreover, they typically rely on optical flow estimation, which adds complexity to modeling and computational costs. To address these issues, we introduce a Motion-Aware Video Frame Interpolation (MA-VFI) network, which directly estimates intermediate optical flow from consecutive frames by introducing a novel hierarchical pyramid module. It not only extracts global semantic relationships and spatial details from input frames with different receptive fields, enabling the model to capture intricate motion patterns, but also effectively reduces the required computational cost and complexity. Subsequently, a cross-scale motion structure is presented to estimate and refine intermediate flow maps by the extracted features. This approach facilitates the interplay between input frame features and flow maps during the frame interpolation process and markedly heightens the precision of the intervening flow delineations. Finally, a discerningly fashioned loss centered around an intermediate flow is meticulously contrived, serving as a deft rudder to skillfully guide the prognostication of said intermediate flow, thereby substantially refining the precision of the intervening flow mappings. Experiments illustrate that MA-VFI surpasses several representative VFI methods across various datasets, and can enhance efficiency while maintaining commendable efficacy.

Acteoside Attenuates Recognition Memory Impairment in CUMS Rats via Regulating Synaptic Plasticity and mTOR Signaling Pathway / El Acteoside Atenúa el Deterioro de la Memoria de Reconocimiento en Ratas ELCI Mediante la Regulación de la Plasticidad Sináptica y la Vía de Señalización mTOR

SUMMARY: We evaluated the role and mechanism of acteoside in the regulation of memory impairment induced by chronic unpredictable mild stress (CUMS). CUMS was used to induce depression in rats and the successful establishment of CUMS model were verified by forced swimming test and sucrose preference test. The Y-maze test and novel object recognition test assessed memory functions. The structural changes in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Immunofluorescence staining and western blotting determined the protein levels. Y-maze test and novel object recognition test showed that there was memory performance impairment in rats of CUMS group, which was improved by the acteoside treatment. HE staining showed that CUMS exposure damaged the structure in the cortex and hippocampus, while the acteoside treatment alleviated the structural changes. Compared with the control group, the levels of BNDF and CREB in the cortex and hippocampus of the CUMS group were significantly decreased. Acteoside significantly reversed the expressions of these proteins in CUMS rats. Meanwhile, compared with the control group, the levels of p-mTOR and p- P70S6K in the cortex and hippocampus of the CUMS group were significantly increased, and these changes were significantly reversed by acteoside. Nevertheless, the effect of acteoside on mTOR signaling was markedly blocked by rapamycin, a specific inhibitor of mTOR signaling. Acteoside can attenuate memory impairment and ameliorate neuronal damage and synaptic plasticity in depression rats probably via inhibiting the mTOR signaling pathway. Acteoside may serve as a novel reagent for the prevention of depression.

Evaluamos el papel y el mecanismo del acteoside en la regulación del deterioro de la memoria inducido por estrés leve crónico impredecible (ELCI). Se utilizó ELCI para inducir depresión en ratas y el establecimiento exitoso del modelo ELCI se verificó mediante una prueba de natación forzada y una prueba de preferencia de sacarosa. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos evaluaron las funciones de la memoria. Los cambios estructurales en la corteza y el hipocampo se observaron mediante tinción con hematoxilina y eosina (HE). La tinción por inmunofluorescencia y la transferencia Western determinaron los niveles de proteína. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos mostraron que había un deterioro del rendimiento de la memoria en ratas del grupo ELCI, que mejoró con el tratamiento con acteósidos. La tinción con HE mostró que la exposición a ELCI dañó la estructura de la corteza y el hipocampo, mientras que el tratamiento con actósidos alivió los cambios estructurales. En comparación con el grupo de control, los niveles de BNDF y CREB en la corteza y el hipocampo del grupo ELCI disminuyeron significativamente. Acteoside revirtió significativamente las expresiones de estas proteínas en ratas ELCI. Mientras tanto, en comparación con el grupo control, los niveles de p-mTOR y p-P70S6K en la corteza y el hipocampo del grupo ELCI aumentaron significativamente, y estos cambios fueron revertidos significativamente ELCI por el acteoside. Sin embargo, el efecto del acteoside sobre la señalización de mTOR fue notablemente bloqueado por la rapamicina, un inhibidor específico de la señalización de mTOR. El acteoside puede atenuar el deterioro de la memoria y mejorar el daño neuronal y la plasticidad sináptica en ratas con depresión, probablemente mediante la inhibición de la vía de señalización mTOR. Acteoside puede servir como un reactivo novedoso para la prevención de la depresión.

Irisin delays the onset of type 1 diabetes in NOD mice by enhancing intestinal barrier.

Type 1 diabetes (T1D), a complex autoimmune disease, is intricately linked to the gut's epithelial barrier function. Emerging evidence emphasizes the role of irisin, an exercise-related hormone, in preserving intestinal integrity. This study investigates whether irisin could delay T1D onset by enhancing the colon intestinal barrier. Impaired colon intestinal barriers were observed in newly diagnosed T1D patients and non-obese diabetic (NOD) mice, worsening with age and accompanied by islet inflammation. Using an LPS-induced colonic inflammation model, a dose-dependent impact of LPS on colon cells irisin expression, secretion, and barrier function was revealed. Exogenous irisin demonstrated remarkable effects, mitigating islet insulitis, enhancing energy expenditure, and alleviating autoimmune symptoms by reducing colon intestinal permeability. Single-cell RNA sequencing (scRNA-seq) highlighted irisin's positive impact on colon epithelial cell clusters, effectively restoring the intestinal barrier. Irisin also selectively modulated bacterial composition, averting potential bacterial translocation. Mechanistically, irisin enhanced colon intestinal barrier tight junction proteins through the AMPK/PI3K/AKT pathway, with FAM120A playing a crucial role. Irisin upregulated MUC3 expression, a protector against damage and inflammation. Harnessing irisin's exercise-mimicking properties suggests therapeutic potential in clinical settings for preventing T1D progression, offering valuable insights into fortifying the colon's intestinal barrier and managing autoimmune conditions associated with T1DM.

Pseudomonas aeruginosa outer membrane vesicle-packed sRNAs can enter host cells and regulate innate immune responses.

Bacterial outer membrane vesicles (OMVs) can package and deliver virulence factors into host cells, which is an important mechanism mediating host-pathogen interactions. It has been reported that small RNAs (sRNAs) can be packed into OMVs with varying relative abundance, which might affect the function and/or stability of host mRNAs. In this study, we used OptiPrep density gradient ultra-high-speed centrifugation to purify OMVs from Pseudomonas aeruginosa. Next, the sequences and abundance of sRNAs were detected by using Small RNA-Seq. In particular, sRNA4518698, sRNA2316613 and sRNA809738 were the three most abundant sRNAs in OMVs, which are all fragments of P. aeruginosa non-coding RNAs. sRNAs were shielded within the interior of OMVs and remained resistant to external RNase cleavage. The miRanda and RNAhybrid analysis demonstrated that those sRNAs could target a large number of host mRNAs, which were enriched in host immune responses by the functions of GO and KEGG enrichment. Experimentally, we demonstrated that the transfection of synthetic sRNA4518698, sRNA2316613, or sRNA809738 could reduce the expression of innate immune response genes in RAW264.7 cells. Together, we demonstrated that P. aeruginosa OMVs sRNAs can regulate innate immune responses. This study uncovered a mechanism in which the OMVs regulate host responses by transferring bacterial sRNAs.

The competitive relationship of scrub plants for water use in the subalpine zone of the Qilian Mountains in China.

Samples of scrub plants and soil were collected from May to October 2019 in the subalpine scrub zone of the Qilian Mountains. Based on measured oxygen isotope values (δ18O) in plant xylem water and soil water, the multivariate linear mixed model (IsoSource) and the proportional similarity index (PS index) were used to analyze the using proportion for each potential water source and the competition relationship for water use of scrub plants in different growing periods and habitats. The results showed that the soil water content gradually decreased with increasing depth of the soil layer, with the maximum value in the soil layer of 0-10 cm. Most of the scrub plants mainly used soil water in the soil layer of 0-30 cm during the different periods of growing season, but Salix sclerophylla Anderss. and Salix oritrepha Schneid. on the semi-sunny slope habitat mainly used soil water in the soil layer of 40-80 cm during the middle period of growing season (July-August), with the proportion of 59.5% and 52.1%, respectively; and Potentilla fruticosa Linn. and Salix cupularis Rehd. on the semi-shady slope habitat mainly used soil water in the soil layer of 30-60 cm during the early period of growing season (May-June), with the proportion of 61.1% and 49.7%, respectively. The competition relationships of scrub plants for water use varied during different periods of growing season (P < 0.05). On the semi-sunny slope habitat, they were fiercest for Salix cupularis Rehd. and Rhododendron thymifolium Maxim., Potentilla fruticosa Linn., and Salix sclerophylla Anderss. during the early period of growing season; Salix cupularis Rehd. and Rhododendron thymifolium Maxim. during the middle period of growing season, and Salix sclerophylla Anderss. and Salix oritrepha Schneid. during the end period of growing season (September-October). On the semi-shady slope habitat, they were fiercest for Salix oritrepha Schneid. and Caragana jubata (Pall.) Poir. during the early period of growing season; Rhododendron przewalskii Maxim. and Rhododendron thymifolium Maxim. during the middle period of growing season; and Salix cupularis Rehd. and Salix oritrepha Schneid. during the end period of growing season. This study reveals the competitive relationship of scrub plants for water use in the subalpine zone and their response to environmental changes, so as to provide theoretical references for the ecological conservation in the ecologically fragile areas of the Qilian Mountains.

Salmonella T3SS-elicited inflammatory innate immune response inhibits type I IFN response in macrophages.

As a gram-negative intracellular bacterial pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium) invades different cell types including macrophages. Its infection in macrophages induces robust innate immune responses that are featured by proinflammatory and type I interferon (IFN) responses. The type III secretion systems (T3SSs) of S. Typhimurium play a crucial role in activating host inflammasome pathways. It has been recognized that the inflammasome pathways inhibit the type I IFN cascade. However, the potential role of T3SS in regulating the type I IFN response and the underlying mechanisms are largely unknown. In this study, we showed that S. Typhimurium infection activated strong proinflammatory, type I IFN and IFN-stimulated genes (ISGs) expression in macrophages. Furthermore, we showed that T3SS-defective S. Typhimurium mutant ΔinvC elicited attenuated inflammatory response but enhanced type I IFN and ISGs expression. Additionally, the inhibition of caspase-1 by a specific inhibitor VX-765 resulted in increased type I IFN response. Moreover, cell-permeable pan-caspase inhibitor Z-VAD-FMK also enhanced the type I IFN response upon S. Typhimurium infection. Intriguingly, compared with exponential phase S. Typhimurium infection, stationary phase bacteria triggered higher levels of type I IFN responses. Finally, the inhibition of caspase-1 by VX-765 substantially increased the intracellular S. Typhimurium burden. In conclusion, we demonstrated that the proinflammatory response induced by S. Typhimurium T3SS can inhibit the type I IFN response, which provides insight into the role of T3SS in orchestrating innate immunity during S. Typhimurium infection.

Effects of season and slope orientation on stable isotopes of different water bodies in the subalpine shrub zone of the eastern Qilian Mountains in China.

The subalpine shrub zone of the Qilian Mountains is an important water-retaining area, and it is crucial to clarify the processes of its hydrological cycle. Therefore, based on the stable isotope values of different water bodies in the subalpine shrub zone of the eastern Qilian Mountains from May to October 2019, the characteristics of δD and δ18O of different water bodies and their hydraulic relationships with each other were studied. The results showed that the stable isotope values of precipitation exhibited the largest fluctuations, while they were the most stable for groundwater. Plant transpiration was stronger than the evaporation of other water bodies. The stable isotope of precipitation was enriched in high temperature and low humidity environments. Isotopic values of plant and soil water were higher and more stable on the semi-sunny slope than on the semi-shady slope. According to the stable isotopes, there was a strong hydraulic relationship between the different water bodies in the study area, and precipitation was the ultimate source of all of them. Precipitation replenished soil water through infiltration. Part of the soil water was absorbed by plants, while the rest continued to infiltrate to replenish groundwater. Groundwater and precipitation replenished the river water.

Isolation and Characterization of Three Pseudomonas aeruginosa Viruses with Therapeutic Potential.

As one of the most common pathogens of opportunistic and hospital-acquired infections, Pseudomonas aeruginosa is associated with resistance to diverse antibiotics, which represents a significant challenge to current treatment modalities. Phage therapy is considered a promising alternative to conventional antimicrobials. The characterization and isolation of new bacteriophages and the concurrent evaluation of their therapeutic potential are fundamental for phage therapy. In this study, we employed an enrichment method and a double-layer agar overlay to isolate bacteriophages that infect P. aeruginosa strains PAO1 and PA14. Three phages (named PA_LZ01, PA_LZ02, and PA_LZ03) were isolated and showed icosahedral heads and contractile tails. Following full-genome sequencing, we found that phage PA_LZ01 contained a genome of 65,367 bp in size and harbored 90 predicted open reading frames (ORFs), phage PA_LZ02 contained a genome of 57,243 bp in size and harbored 75 predicted ORFs, and phage PA_LZ03 contained a genome of 57,367 bp in size and carried 77 predicted ORFs. Further comparative analysis showed that phage PA_LZ01 belonged to the genus Pbunavirus genus, phage PA_LZ02 belonged to the genus Pamexvirus, and phage PA_LZ03 belonged to the family Mesyanzhinovviridae. Next, we demonstrated that these phages were rather stable at different temperatures and pHs. One-step growth curves showed that the burst size of PA_LZ01 was 15 PFU/infected cell, and that of PA_LZ02 was 50 PFU/infected cell, while the titer of PA_LZ03 was not elevated. Similarly, the biofilm clearance capacities of PA_LZ01 and PA_LZ02 were also higher than that of PA_LZ03. Therapeutically, PA_LZ01 and PA_LZ02 treatment led to decreased bacterial loads and inflammatory responses in a mouse model. In conclusion, we isolated three phages that can infect P. aeruginosa, which were stable in different environments and could reduce bacterial biofilms, suggesting their potential as promising candidates to treat P. aeruginosa infections. IMPORTANCE Phage therapy is a promising therapeutic option for treating bacterial infections that do not respond to common antimicrobial treatments. Biofilm-mediated infections are particularly difficult to treat with traditional antibiotics, and the emergence of antibiotic-resistant strains has further complicated the situation. Pseudomonas aeruginosa is a bacterial pathogen that causes chronic infections and is highly resistant to many antibiotics. The library of phages that target P. aeruginosa is expanding, and the isolation of new bacteriophages is constantly required. In this study, three bacteriophages that could infect P. aeruginosa were isolated, and their biological characteristics were investigated. In particular, the isolated phages are capable of reducing biofilms formed by P. aeruginosa. Further analysis indicates that treatment with PA_LZ01 and PA_LZ02 phages reduces bacterial loads and inflammatory responses in vivo. This study isolated and characterized bacteriophages that could infect P. aeruginosa, which offers a resource for phage therapy.

[Comparison of clinical effects of different irrigant solutions combined with different agitation techniques in the treatment of chronic apical periodontitis with fistula].

PURPOSE: To evaluate the effect of combination of auxiliary irrigation technology and root canal irrigation solution in the treatment of chronic apical periodontitis with fistula, and try to seek a more effective and minimally invasive therapeutic strategy. METHODS: One hundred and fifty patients with fistulous chronic apical periodontitis who were diagnosed in Hefei Stomatological Hospital from January 2021 to January 2022 were randomly divided into 6 groups, 25 cases in each group. The 6 groups were as follows, group A: 0.5%NaOCl +ultrasonically activated irrigation; Group B: 1.0%NaOCl+ultrasonically activated irrigation; Group C: 2.0%CHX+ultrasonically activated irrigation; Group D: 0.5%NaOCl+sonic activation; Group E: 1.0%NaOCl+sonic activation; Group F: 2.0%CHX+sonic activation. The fistula healing time, treatment effect and postoperative pain were observed in each group. The data were analyzed with SPSS 20.0 software package. RESULTS: In terms of fistula healing, the 10-day fistula healing rate of group E and group F was higher than that of group A and group D，and the difference was statistically significant(P＜0.05); but there was no significant difference between group E and group F (P＞0.05). The effective rate at 1 month after operation in group A was lower, and the difference was significant (P＜0.05). In terms of postoperative pain, the VAS score of group A was lower than that of group E and group F at all time points, and the difference was statistically significant(P＜0.05). CONCLUSIONS: In the treatment of chronic apical periodontitis with fistula, 1.0% NaOCl or 2.0% CHX combined with ultrasonically activated irrigation or sonic activation obtain a better short-term effect，of which the sonic activation group can also obtain early healing of the fistula, but the incidence of postoperative pain is higher when sonic activation is used.

Manganese potentiates lipopolysaccharide-induced innate immune responses and septic shock.

Divalent metal ions such as magnesium (Mg2+), manganese (Mn2+), and zinc (Zn2+) play important roles in regulating innate immune responses. Lipopolysaccharide stimulation led to increased intracellular Mn and Zn in macrophages. However, the effect of those metal ions in regulating lipopolysaccharide-induced innate immune responses remains unclear. Here, we uncovered that both Mn2+ and Zn2+ have immunostimulatory effects, which could potentiate the lipopolysaccharide-induced expression of interferon-stimulated genes (ISGs), cytokines and pro-inflammatory genes in a dose-dependent manner. Enhancement of lipopolysaccharide-induced innate immune gene expression by Mn2+ varies between 10 % and 900 %. Conversely, the chelating of Mn2+ almost totally diminished Mn2+-enhanced lipopolysaccharide-induced gene expression. In addition, Mn2+ exerted its ability to potentiate LPS-induced innate immune gene expression regardless of slight pH changes. Importantly, we found that Mn2+ potentiates lipopolysaccharide-induced immune responses independent of TLR4 but partially relies on cGAS-STING pathway. Further in vivo study showed that colloidal Mn2+ salt (Mn jelly [MnJ]) pretreatment exacerbated lipopolysaccharide-induced septic shock and mice death. In conclusion, we demonstrated that Mn2+ plays an essential role in boosting lipopolysaccharide-induced innate immune responses. These findings greatly expand the current understanding of the immunomodulatory potential of divalent metal Mn2+ and may provide a potential therapeutic target to prevent excessive immune responses.

Only Sunda and Chinese pangolin (Pholidota) are naturally distributed in China.

Actually, only two pangolin species occur naturally in China, namely the Chinese pangolin (Manis pentadactyla) and the Sunda pangolin (Manis javanica). The Sunda pangolin was found to occur naturally in Yunnan, China, but only with a narrow distribution in the Xishuangbanna and Pu'er City. The Indian pangolin (Manis crassicaudata) did not occur in China. The previous claim that this species is naturally distributed in China was found to originate from a mistake in the book "The Mammals of China and Mongolia" written by Allen in 1938.

A Theoretical Review on the Impact of EFL/ESL Students' Self-Sabotaging Behaviors on Their Self-Esteem and Academic Engagement.

Learner emotions have been considerably emphasized in SLA research and practice with the advent of positive psychology. This has led to a surge of scholarly interest in this strand of research over the past years all around the world. However, the impact of students' negative emotions such as self-sabotage that actually occur in english as a foreign language (EFL) classrooms on the construction and development of positive learner emotions like self-esteem and academic engagement has been mostly overlooked by second/foreign language researchers. Against this shortcoming, the present review article presented the theoretical and empirical underpinnings of these three crucial variables in SLA focusing on their conceptualizations, dimensions, typologies, related studies, and research gaps. Finally, the study offers a number of practical implications to [EFL/english as a second language (ESL)] teachers, students, teacher trainers, and SLA researchers in order to increase their awareness of learner emotions and the power of such feelings in language teaching and learning processes.

Salmonella Induces the cGAS-STING-Dependent Type I Interferon Response in Murine Macrophages by Triggering mtDNA Release.

Salmonella enterica serovar Typhimurium (S. Typhimurium) elicited strong innate immune responses in macrophages. To activate innate immunity, pattern recognition receptors (PRRs) in host cells can recognize highly conserved pathogen-associated molecular patterns (PAMPs). Here, we showed that S. Typhimurium induced a robust type I interferon (IFN) response in murine macrophages. Exposure of macrophages to S. Typhimurium activated a Toll-like receptor 4 (TLR4)-dependent type I IFN response. Next, we showed that type I IFN and IFN-stimulated genes (ISGs) were elicited in a TBK1-IFN-dependent manner. Furthermore, cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and immune adaptor protein stimulator of interferon genes (STING) were also required for the induction of type I IFN response during infection. Intriguingly, S. Typhimurium infection triggered mitochondrial DNA (mtDNA) release into the cytosol to activate the type I IFN response. In addition, we also showed that bacterial DNA was enriched in cGAS during infection, which may contribute to cGAS activation. Finally, we showed that cGAS and STING deficient mice and cells were more susceptible to S. Typhimurium infection, signifying the critical role of the cGAS-STING pathway in host defense against S. Typhimurium infection. In conclusion, in addition to TLR4-dependent innate immune response, we demonstrated that S. Typhimurium induced the type I IFN response in a cGAS-STING-dependent manner and the S. Typhimurium-induced mtDNA release was important for the induction of type I IFN. This study elucidated a new mechanism by which bacterial pathogen activated the cGAS-STING pathway and also characterized the important role of cGAS-STING during S. Typhimurium infection. IMPORTANCE As one of the most common foodborne transmitted zoonotic pathogens, S. Typhimurium infection causes diarrheal disease in humans and animals. S. Typhimurium infection has been implicated as an inducer for the type I interferon (IFN) response in macrophages, but the mechanisms are not fully understood. In this study, we reported that in addition to TLR4-dependent response, the cytosolic surveillance pathway (CSP) cGAS-STING is also required for the activation of type I IFN response during S. Typhimurium infection. We further showed that the infection of S. Typhimurium triggered mtDNA release into the cytosol, which induces the type I IFN response. In addition, physical interactions between cGAS and S. Typhimurium DNA have been identified in the context of infection. Importantly, we also provided convincing in vivo and in vitro evidence that the cGAS-STING pathway was potently implicated in the host defense against S. Typhimurium infection. Together, we uncovered a mechanism by which type I IFN response is elicited during S. Typhimurium infection in murine macrophages in an mtDNA-cGAS-STING-dependent manner.

Contribution of recycled moisture to precipitation and its influencing factors in the subalpine zone of Qilian Mountains.

Recycled moisture, the part of precipitating vapor that comes from surface evapotranspiration, plays an important role in the hydrological process and the feedback of the land surface-atmosphere system. In this study, we use the δ2H and δ18O data of precipitation, plant water, and surface water systematically collected in the subalpine area of the Qilian Mountains from May to October, 2019, and assess the contribution of recycled moisture to precipitation based on the three-component isotopic mixing model. The results indicated that the main source of precipitating vapor comes from the advected vapor, and its contribution reaches up to 87.8 ± 1.6%. The contribution of local recycled moisture is 12.2 ± 1.6%, in which the proportion of transpiration and evaporation are 8.9 ± 0.6% and 3.3 ± 1.0%, respectively. In terms of the correlation between recycled moisture and its influencing factors, the temperature has a positive effect on evapotranspiration and promotes moisture recycling, while precipitation and humidity have a certain inhibition effect on evapotranspiration and reduce the contribution of recycled moisture.

Colony composition and nutrient analysis of Polyrhachis dives ants, a natural prey of the Chinese pangolin (Manis pentadactyla).

The Chinese pangolin (Manis pentadactyla) is a critically endangered mammal with a highly specialized diet. To enhance nutritional knowledge of its diet, we analyzed the colony composition of a nest of Polyrhachis dives ants, which is the key natural prey in the Chinese pangolin's diet. In addition, we determined the nutrient composition of the total colony compared with adult ants. Nutrients quantified in this study included: crude protein, crude fat, carbohydrate, and amino acids, minerals, and vitamins, as well as formic acid and chitin, which have not been reported in previous diet studies. Our results showed that the colony consisted of adults (82%), pupae (10%), larvae (7%), and eggs (1%) (fresh mass). Both the total colony and adult ants, respectively, contained high concentrations of crude protein (62.97% and 64.68%), chitin (49.25% and 60.40%), crude fat (10.12% and 9.91%) (dry matter basis), and formic acid (2.06% and 3.07%) (fresh mass). This implies that Chinese pangolin might prefer prey with high protein, high chitin, low fat, and low formic acid content. Colony and adult ants differed in chemical composition in many aspects, thus it might be unsuitable to feed Chinese pangolin with only adult ants. Chitin and formic acid may play important roles in the diet and selectivity of Chinese pangolin. This study provides reference information that may be useful for developing better artificial diets with more comprehensive nutrient compositional data to meet the nutritional requirements of the Chinese pangolin under managed feeding programs.

Neutrophil CD64: a potential biomarker for the diagnosis of infection in patients with haematological malignancies.

METHODS: The clinical data of 76 patients with haematological malignancies and infection who were treated in our department between January 2014 and October 2019 were retrospectively analysed. To evaluate the diagnostic value of some biomarkers, infection indexes such as white blood cell count (WBC), neutrophil count (NEUT), neutrophil CD64 and procalcitonin (PCT) were compared across the patients with confirmed infection status and infection-control status. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were also determined. RESULTS: The WBC and NEUT did not differ significantly, whereas the neutrophil CD64 and PCT levels were significantly elevated in patients with a confirmed infection status (p < 0.05), with sensitivity of 31.0%, 45.2%, 76.2% and 50%, respectively, and specificity of 90.5%, 69%, 71.4% and 64.3%, respectively. The AUC of WBC, NEUT, neutrophil CD64 and PCT was 0.528, 0.517, 0.844 and 0.599, respectively. Further highlighting their diagnostic value, the neutrophil CD64 and PCT levels in neutropenia patients were significantly upregulated in patients with infection status (p < 0.05) but the WBC and NEUT were unchanged, with sensitivity of 73.7%, 63.2%, 68% and 68.4%, respectively, and specificity of 68.4%, 52.6%, 57.9% and 63.2%, respectively. The AUC of neutrophil CD64, PCT, WBC and NEUT was 0.864, 0.593, 0.419 and 0.403, respectively. CONCLUSION: These results indicate that neutrophil CD64 is a promising biomarker with superior sensitivity and specificity for diagnosing infection in patients with haematological malignancies, especially neutropenia patients.