Characterizing the metabolome and microbiome at giant panda scent marking sites during the mating season.

Scent marking sites served as a primary means of chemical communication for giant pandas, enabling intraspecific communication. We integrated metabolomics and high-throughput sequencing techniques to examine the non-targeted metabolome and microbial community structure of scent marking sites and feces in the field. Integrative analysis revealed a more comprehensive array of chemical compounds compared to previous investigations, including ketones, acids, heterocycles, alcohols, and aldehydes. Notably, specific compounds such as 2-decenal, (E)-, octanal, decanal, L-α-terpineol, vanillin, and nonanal emerged as potential key players in scent signaling. Intriguingly, our study of the microbial domain identified dominant bacterial species from the Actinobacteria, Bacteroidetes, and Proteobacteria phyla, likely orchestrating metabolic processes at scent marking sites. Comparative analyses showed, for the first time, that feces do not share the same functions as scent markers, indicating distinct functional roles. This research deepens scientific understanding of chemical communication in wild pandas.

Two-dimensional perovskite templates for durable, efficient formamidinium perovskite solar cells.

We present a design strategy for fabricating ultrastable phase-pure films of formamidinium lead iodide (FAPbI3) by lattice templating using specific two-dimensional (2D) perovskites with FA as the cage cation. When a pure FAPbI3 precursor solution is brought in contact with the 2D perovskite, the black phase forms preferentially at 100°C, much lower than the standard FAPbI3 annealing temperature of 150°C. X-ray diffraction and optical spectroscopy suggest that the resulting FAPbI3 film compresses slightly to acquire the (011) interplanar distances of the 2D perovskite seed. The 2D-templated bulk FAPbI3 films exhibited an efficiency of 24.1% in a p-i-n architecture with 0.5-square centimeter active area and an exceptional durability, retaining 97% of their initial efficiency after 1000 hours under 85°C and maximum power point tracking.

The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases.

Interleukin-6 (IL-6) is a pleiotropic cytokine and exerts its complex biological functions mainly through three different signal modes, called cis-, trans-, and cluster signaling. When IL-6 binds to its membrane or soluble receptors, the co-receptor gp130 is activated to initiate downstream signaling and induce the expression of target genes. In the liver, IL-6 can perform its anti-inflammatory activities to promote hepatocyte reprogramming and liver regeneration. On the contrary, IL-6 also exerts the pro-inflammatory functions to induce liver aging, fibrosis, steatosis, and carcinogenesis. However, understanding the roles and underlying mechanisms of IL-6 in liver physiological and pathological processes is still an ongoing process. So far, therapeutic agents against IL­6, IL­6 receptor (IL­6R), IL-6-sIL-6R complex, or IL-6 downstream signal transducers have been developed, and determined to be effective in the intervention of inflammatory diseases and cancers. In this review, we summarized and highlighted the understanding of the double-edged effects of IL-6 in liver homeostasis, aging, inflammation, and chronic diseases, for better shifting the "negative" functions of IL-6 to the "beneficial" actions, and further discussed the potential therapeutic effects of targeting IL-6 signaling in the clinics.

Upconversion Emission and Dual-Mode Sensing Characteristics of NaYF4:Yb3+/Er3+ Microcrystals at High and Ultralow Temperatures.

In this study, we investigate micrometer-sized NaYF4 crystals double-doped with Yb3+/Er3+ lanthanide ions, designed for temperature-sensing applications. In contrast to previous studies, which focused predominantly on the high-temperature regime, our investigation spans a comprehensive range of both high and ultralow temperatures. We explore the relationship between temperature and the upconversion luminescence (UCL) spectra in both frequency and time domains. Our findings highlight the strong dependence of these spectral characteristics of lanthanide-doped NaYF4 crystals on temperature. Furthermore, we introduce a dual-mode luminescence temperature measurement technique, leveraging the upconversion emission intensity ratio for both green and red emissions. This study also examines the correlation between temperature sensing, energy level disparities, and thermal coupling in Er3+ ions across various temperature scales. Our research contributes to advancing the understanding and application of lanthanide-doped materials, setting a foundation for future innovations in temperature sensing across diverse fields.

Four sulfur-containing compounds with anti-colon cancer effect from marine-derived fungus Aspergillus terreus.

Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1-21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30µM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.

Mechanism and functional verification of genes by virulence factors of P. gingivalis in ferroptosis.

OBJECTIVE: Porphyromonas gingivalis (P. gingivalis) is a key etiological agent in periodontitis and functions as a facultative intracellular microorganism and involves many virulence factors. These virulence factors participate in multiple intracellular processes, like ferroptosis, the mechanistic underpinnings remain to be elucidated. Aim of this study was to investigate the effects of virulence factors on the host cells. DESIGN: Human umbilical vein endothelial cells (HUVECs) were treated with 4% paraformaldehyde-fixed P. gingivalis, and subsequent alterations in gene expression were profiled via RNA-seq. Further, the molecules associated with ferroptosis were quantitatively analyzed using qRT-PCR and Western blot. RESULTS: A total of 1125 differentially expressed genes (DEGs) were identified, encompassing 225 upregulated and 900 downregulated. Ferroptosis was conspicuously represented in the kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, with notable upregulation of Heme oxygenase 1 (HMOX1), Ferritin light chain (FTL), and Solute carrier family 3 member 2 (SLC3A2) and downregulation of Scavenger receptor class A member 5 (SCARA5) and glutaminase (GLS). Random selection of DEGs for validation through qRT-PCR corroborated the RNA-Seq data (R2 = 0.93). Kelch like ECH associated protein 1 (Keap1) protein expression decreased after 4 and 8 h, while NFE2 like bZIP transcription factor 2 (Nrf2) and HMOX1 were elevated, with significant nuclear translocation of Nrf2. CONCLUSIONS: The virulence factors of P. gingivalis may potentially instigating ferroptosis through activation of the Keap1-Nrf2-HMOX1 signaling cascade, in conjunction with modulating the expression of other ferroptosis-associated elements. Further research is necessary to achieve a thorough comprehension of these complex molecular interactions.

Exercise promotes brain health: a systematic review of fNIRS studies.

Exercise can induce brain plasticity. Functional near-infrared spectroscopy (fNIRS) is a functional neuroimaging technique that exploits cerebral hemodynamics and has been widely used in the field of sports psychology to reveal the neural mechanisms underlying the effects of exercise. However, most existing fNIRS studies are cross-sectional and do not include exercise interventions. In addition, attributed to differences in experimental designs, the causal relationship between exercise and brain functions remains elusive. Hence, this systematic review aimed to determine the effects of exercise interventions on alterations in brain functional activity in healthy individuals using fNIRS and to determine the applicability of fNIRS in the research design of the effects of various exercise interventions on brain function. Scopus, Web of Science, PubMed, CNKI, Wanfang, and Weipu databases were searched for studies published up to June 15, 2021. This study was performed in accordance with the PRISMA guidelines. Two investigators independently selected articles and extracted relevant information. Disagreements were resolved by discussion with another author. Quality was assessed using the Cochrane risk-of-bias method. Data were pooled using random-effects models. A total of 29 studies were included in the analysis. Our results indicated that exercise interventions alter oxygenated hemoglobin levels in the prefrontal cortex and motor cortex, which are associated with improvements in higher cognitive functions (e.g., inhibitory control and working memory). The frontal cortex and motor cortex may be key regions for exercise-induced promotion of brain health. Future research is warranted on fluctuations in cerebral blood flow during exercise to elucidate the neural mechanism underlying the effects of exercise. Moreover, given that fNIRS is insensitive to motion, this technique is ideally suited for research during exercise interventions. Important factors include the study design, fNIRS device parameters, and exercise protocol. The examination of cerebral blood flow during exercise intervention is a future research direction that has the potential to identify cortical hemodynamic changes and elucidate the relationship between exercise and cognition. Future studies can combine multiple study designs to measure blood flow prior to and after exercise and during exercise in a more in-depth and comprehensive manner.

Time-varying propagation model and dynamic-feedback-phase correction for multiplexed orbital angular momentum beams in atmospheric turbulence.

Freespace optical (FSO) communication in an outdoor setting is complicated by atmospheric turbulence (AT). A time-varying (TV) multiplexed orbital angular momentum (OAM) propagation model to consider AT under transverse-wind conditions is formulated for the first time, and optimized dynamic correction periods for various TV AT situations are found to improve the transmission efficiency. The TV nature of AT has until now been neglected from modeling of OAM propagation models, but it is shown to be important. First, according to the Taylor frozen-turbulence hypothesis, a series of AT phase screens influenced by transverse wind are introduced into the conventional angular-spectrum propagation analysis method to model both the temporal and spatial propagation characteristics of multiplexed OAM beams. Our model shows that while in weak TV AT, the power standard deviation of lower-order modes is usually smaller than that of higher-order modes, the phenomena in strong TV AT are qualitatively different. Moreover, after analyzing the effective time of each OAM phase correction, optimized dynamic correction periods for a dynamic feedback communication link are obtained. An optimized result shows that, under the moderate TV AT, both a system BER within the forward-error-correction limit and a low iterative computation volume with 6% of the real-time correction could be achieved with a correction period of 0.18 s. The research emphasizes the significance of establishing a TV propagation model for exploring the effect of TV AT on multiplexed OAM beams and proposing an optimized phase-correction mechanism to mitigate performance degradation caused by TV AT, ultimately enhancing overall transmission efficiency.

Influence of the community assemblage on sulfur distributions in the South China sea.

Marine distribution of dimethylsulfoniopropionate (DMSP) and its cleavage product dimethyl sulfide (DMS) is greatly affected by the community structures of bacteria, phytoplankton, and zooplankton. Spatial distributions of dissolved and particulate DMSP (DMSPd,p), and DMS were measured and their relationships with DMSP lyase activity (DLA), abundance of DMSP-consuming bacteria (DCB), and the community structures of phytoplankton, zooplankton, and bacteria were determined during summer in the South China Sea (SCS). The depth distributions of DMSPd,p exhibited a similar trend with Chl a, reaching their maxima in the mixing layer. The DMS concentration was positively correlated with DCB abundance and DLA, indicating that DCB and DMSP lyase had a significant effect on DMS production. High DMS concentrations in the horizontal distribution coincided with high DCB abundance and DLA and may be due to the rapid growth of phytoplankton resulting from the high dissolved inorganic nitrogen concentration brought by the cold vortices. Moreover, the highest copepod abundance at station G3 coincided with the highest DMS concentrations there among stations B4, F2, and G3. These results suggest that copepod may play an important role in DMS production. The bacterial SAR11 clade was positively correlated with DLA, indicating its significant contribution to DMSP degradation in the SCS. These findings contribute to the understanding of the effect of the community assemblage on DMSP/DMS distributions in the SCS dominated by mesoscale vortices.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Topotactic Conversion of Titanium-Oxo Clusters to a Stable TOC-Based Metal-Organic Framework with the Selective Adsorption of Cationic Dyes.

Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti6O6(OiPr)8(TTFTC)(phen)2]2 (1, where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1, in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity (qex) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1.

Genome-scale transcriptional activation by non-homologous end joining-mediated integration in Yarrowia lipolytica.

BACKGROUND: Genome-scale screening can be applied to efficiently mine for unknown genes with phenotypes of interest or special functions. It is also useful to identify new targets for engineering desirable properties of cell factories. RESULTS: Here, we designed a new approach for genome-scale transcription activation using non-homologous end joining (NHEJ)-mediated integration in Yarrowia lipolytica. We utilized this approach to screen for genes that, upon activation, confer phenotypes including improved acetic acid tolerance and xylose metabolism. The candidates were validated using gene overexpression, and functional changes including improved growth performance under multiple stressors and activated pentose metabolism were identified. CONCLUSIONS: This study provides a simple and effective approach to randomly activate endogenous genes and mine for key targets associated with phenotypes of interest. The specific gene targets identified here will be useful for cell factory construction and biorefining lignocellulose.

Xinshubao tablet rescues cognitive dysfunction in a mouse model of vascular dementia: Involvement of neurogenesis and neuroinflammation.

Vascular dementia (VaD) represents a severe cognitive dysfunction syndrome closed linked to cardiovascular function. In the present study, we assessed the potential of Xinshubao tablet (XSB), a traditional Chinese prescription widely used for cardiovascular diseases, to mitigate neuropathological damage in a mouse model of VaD and elucidated the underlying mechanisms. Our findings revealed that oral administration of XSB rescued the cardiac dysfunction resulting from bilateral common carotid artery stenosis (BCAS), improved the cerebral blood flow (CBF) and cognitive function, reduced white matter injury, inhibited excessive microglial and astrocytic activation, stimulated hippocampal neurogenesis, and reduced neural apoptosis in the brains of BCAS mice. Mechanistically, RNA-seq analysis indicated that XSB treatment was significantly associated with neuroinflammation, vasculature development, and synaptic transmission, which were further confirmed by q-PCR assays. Western blot results revealed that XSB treatment hindered the nuclear translocation of nuclear factor-κB (NF-κB), thereby suppressing the NF-κB signaling pathway. These results collectively demonstrated that XSB could ameliorate cognitive dysfunction caused by BCAS through regulating CBF, reducing white matter lesions, suppressing glial activation, promoting neurogenesis, and mitigating neuroinflammation. Notably, the NF-κB signaling pathway emerged as a pivotal player in this mechanism.

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

Development of genetic markers in Yarrowia lipolytica.

The oleaginous yeast Yarrowia lipolytica represents a potential microbial cell factory for the recombinant production of various valuable products. Currently, the commonly used selection markers for transformation in Y. lipolytica are limited, and successive genetic manipulations are often restricted by the number of available selection markers. In our study, we developed a dominant marker, dsdA, which encodes a D-serine deaminase for genetic manipulation in Y. lipolytica. In Y. lipolytica, this marker confers the ability to use D-serine as a nitrogen source. In addition, the selection conditions of several infrequently used dominant markers including bleoR (zeocin resistance), kanMX (G418 resistance), and guaB (mycophenolic acid resistance) were also analyzed. Our results demonstrated that these selection markers can be used for the genetic manipulation of Y. lipolytica and their selection conditions were different for various strains. Ultimately, the selection markers tested here will be useful to expand the genetic toolbox of Y. lipolytica. KEY POINTS: • The dsdA from Escherichia coli was developed as a dominant marker. • The applicability of several resistance markers in Y. lipolytica was determined. • We introduced the Cre/mutant lox system for marker recycling.

Effects of nanoplastics exposure on ingestion, life history traits, and dimethyl sulfide production in rotifer Brachionus plicatilis.

Microplastics (MPs) and nanoplastics (NPs) have gained global concern due to their detrimental effects on marine organisms. We investigated the effects of 80 nm polystyrene (PS) NPs on life history traits, ingestion, and dimethyl sulfide (DMS) and dimethylsulfoniopropionate (DMSP) production in the rotifer Brachionus plicatilis. Fluorescently labeled 80 nm PS NPs were ingested by the rotifer B. plicatilis and accumulated in the digestive tract. The lethal rates of B. plicatilis exposed to NPs were dose-dependent. High concentrations of PS NPs exposure had negative effects on developmental duration, leading to prolonged embryonic development and pre-reproductive periods, shortened reproductive period, post-reproductive period, and lifespan in B. plicatilis. High concentrations of PS NPs exposure inhibited life table demographic parameters such as age-specific survivorship and fecundity, generation time, net reproductive rate, and life expectancy. Consequently, the population of B. plicatilis was adversely impacted. Furthermore, exposure to PS NPs resulted in a reduced ingestion rate in B. plicatilis, as well as a decreased in DMS, particulate DMSP (DMSPp) concentration, and DMSP lyase activity (DLA), which exhibited a dose-response relationship. B. plicatilis grazing promoted DLA and therefore increased DMS production. PS NPs exposure caused a decline in the increased DMS induced by rotifer grazing. Our results help to understand the ecotoxicity of NPs on rotifer and their impact on the biogeochemical cycle of dimethylated sulfur compounds.

Immediate effect of recurrent laryngeal nerve stimulation in patients with idiopathic unilateral vocal fold paralysis.

BACKGROUND: There is a lack of effective treatment for idiopathic unilateral vocal fold paralysis (IUVFP). A better phonation was reported by patients after laryngeal nerve stimulation during our clinical examination. OBJECTIVES: This study aims to investigate immediate effect of recurrent laryngeal nerve (RLN) stimulation on phonation in patients with IUVFP. MATERIAL AND METHODS: Sixty-two patients with clinically identified IUVFP underwent RLN stimulation with needle electrodes. Laryngoscopy, acoustic analysis, and voice perception assessment were performed for quantitative comparison of vocal function and voice quality before and after the intervention. RESULTS: Laryngoscopic images showed a larger motion range of the paralyzed vocal fold (p < .01) and better glottal closure (p < .01) after RLN stimulation. Acoustic analysis revealed that the dysphonia severity index increased significantly (p < .01) while the jitter and shimmer decreased after the intervention (p < .05). According to perceptual evaluation, RLN stimulation significantly increased RBH grades in patients with IUVFP (p < .01). Furthermore, the improvement in voice perception had a moderate positive correlation with the decrease in the glottal closure. CONCLUSIONS AND SIGNIFICANCE: This study shows a short-term improvement of phonation in IUVFP patients after RLN stimulation, which provides proof-of-concept for trialing a controlled delivery of RLN stimulation and assessing durability of any observed responses.

Guanylate-binding protein 5-mediated cell-autonomous immunity suppresses inflammation in dental pulpitis: An in vitro study.

AIM: Guanylate-binding protein 5 (GBP5) is an interferon (IFN)-inducible GTPase that plays a crucial role in the cell-autonomous immune response against microbial infections. In this study, we investigated the immunoregulatory role of GBP5 in the pathogenesis of dental pulpitis. METHODOLOGY: Gene-set enrichment analysis (GSEA) was utilized to evaluate the IFN-γ signalling pathway, and the differential expression of GBP mRNA in normal versus inflamed dental pulp tissues was screened, based on Gene Expression Omnibus (GEO) datasets associated with pulpitis. Both normal pulp tissues and inflamed pulp tissues were used for experiments. The expression of IFNs and GBPs was determined by qRT-PCR. Immunoblotting and double immunofluorescence were performed to examine the cellular localization of GBP5 in dental pulp tissues. For the functional studies, IFN-γ priming or lentivirus vector-delivered shRNA was used to, respectively, overexpress or knock down endogenous GBP5 expression in human dental pulp stem cells (HDPSCs). Subsequently, LPS was used to stimulate HDPSCs (overexpressing or with knocked-down GBP5) to establish an in vitro model of inflammation. qRT-PCR and ELISA were employed to examine the expression of proinflammatory cytokines (IL-6, IL-8 and IL-1ß) and cyclooxygenase 2 (COX2). Every experiment has three times of biological replicates and three technical replicates, respectively. Statistical analysis was performed using the Student's t-test and one-way ANOVA, and a p-value of <.05 was considered statistically significant. RESULTS: GSEA analysis based on the GEO dataset revealed a significant activation of the IFN-γ signalling pathway in the human pulpitis group. Among the human GBPs evaluated, GBP5 was selectively upregulated in inflamed dental pulp tissues and predominantly expressed in dental pulp cells. In vitro experiments demonstrated that IFN-γ robustly induced the expression of GBP5 in HDPSCs. Knockdown of GBP5 expression in HDPSCs significantly amplified the LPS-induced upregulation of inflammatory mediators (IL-6, IL-8, IL-1ß and COX2) both with and without IFN-γ priming. CONCLUSION: Our findings demonstrated that GBP5 partook in the pathogenesis of dental pulpitis. The involvement of GBP5 in pulpitis appeared to coordinate the regulation of inflammatory cytokines. Knockdown of GBP5 contributed to the exacerbation of LPS-mediated inflammation.

Sensory nerves, but not sympathetic nerves, promote reparative dentine formation after dentine injury via CGRP-mediated angiogenesis: An in vivo study.

AIM: Dental pulp is richly innervated by nerve fibres, which are mainly involved in the sensation of pain. Aside from pain sensation, little is known regarding the role of dental innervation in reparative dentine formation. We herein generated a mouse model of experimental dentine injury to examine nerve sprouting within the odontoblast and subodontoblastic layers and investigated the potential effects of this innervation in reparative dentinogenesis. METHODOLOGY: Mouse tooth cavity model (bur preparation + etching) was established, and then nerve sprouting, angiogenesis and reparative dentinogenesis were determined by histological and immunofluorescent staining at 1, 3, 7, 14 and 28 days postoperatively. We also established the mouse-denervated molar models to determine the role of sensory and sympathetic nerves in reparative dentinogenesis, respectively. Finally, we applied calcitonin gene-related peptide (CGRP) receptor antagonist to analyse the changes in angiogenesis and reparative dentinogenesis. RESULTS: Sequential histological results from dentine-exposed teeth revealed a significant increase in innervation directly beneath the injured area on the first day after dentine exposure, followed by vascularisation and reparative dentine production at 3 and 7 days, respectively. Intriguingly, abundant type H vessels (CD31+ Endomucin+ ) were present in the innervated area, and their formation precedes the onset of reparative dentine formation. Additionally, we found that sensory denervation led to blunted angiogenesis and impaired dentinogenesis, while sympathetic denervation did not affect dentinogenesis. Moreover, a marked increase in the density of CGRP+ nerve fibres was seen on day 3, which was reduced but remained elevated over the baseline level on day 14, whereas the density of substance P-positive nerve fibres did not change significantly. CGRP receptor antagonist-treated mice showed similar results as those with sensory denervation, including impairments in type H angiogenesis, which confirms the importance of CGRP in the formation of type H vessels. CONCLUSIONS: Dental pulp sensory nerves act as an essential upstream mediator to promote angiogenesis, including the formation of type H vessels, and reparative dentinogenesis. CGRP signalling governs the nerve-vessel-reparative dentine network, which is mostly produced by newly dense sensory nerve fibres within the dental pulp.