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Glioma is one of the most prevalent primary intracranial tumors, and biomarker testing offers a non-invasive modality with high diagnostic efficiency. The aim of this meta-analysis is to evaluate the diagnostic effectiveness of exosomes as biomarkers for glioma. We included 16 studies on exosomes as biomarkers for gliomas. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for 25 biomarkers across these 16 studies were as follows: 82% (95% CI: 0.77-0.86), 91% (95% CI: 0.86-0.94), 9.10 (95% CI: 5.64-14.68), 0.20 (95% CI: 0.16-0.25), 45.94 (95% CI: 25.40-83.09), and 0.92 (95% CI: 0.89-0.94), respectively. Meta-regression indicated that biomarker analysis, biomarker type, and sample size may be sources of heterogeneity. Subgroup analysis suggested that ultracentrifugation (UC) was a better method for extracting exosomes. miRNA and other RNA groups (sncRNA, lncRNA, circRNA) provided higher SEN (0.88 vs. 0.84 vs. 0.78) compared to proteins. This study demonstrates the superior diagnostic efficacy of exosomes as biomarkers for gliomas, with high accuracy in diagnosing gliomas.

Background: The retrospective study examined changes in the root length and alveolar bone surrounding maxillary incisors in patients with skeletal Class III malocclusion treated by surgical orthodontic treatment with either fixed appliances (FAs) or clear aligners (CAs)., Methods: A total of 60 subjects were divided based on appliance type used. Cone beam computed tomography scans were taken at three stages: before treatment, after presurgical orthodontic treatment, and post-treatment for both groups. Vertical alveolar bone level and horizontal alveolar bone thickness (ABT) were measured at four heights (3, 6, and 9 mm from the cementoenamel junction, and the root apex), along with root length, at these time points., Results: Both groups showed a decrease in root length, with the CA group experiencing a significantly smaller reduction (0.4 ± 0.79 mm) compared with the FA group (0.64 ± 0.8 mm; P = 0.02). The FA group demonstrated more significant reduction in palatal ABT (P < 0.05) and greater root resorption, whereas the CA group exhibited considerable labial marginal bone resorption (P = 0.007) and a notable decrease in labiolingual inclination (P = 0.042)., Conclusions: The findings suggest that FA and CA might lead to decreased ABT and significant root resorption, with FA therapy likely resulting in more pronounced effects. Both modalities led to notable vertical bone loss, particularly, on the labial side of the maxillary incisors in the CA group during postsurgical orthodontic treatment. Preventing iatrogenic deterioration of periodontal support surrounding the incisors is crucial during presurgical and postsurgical phases., (Copyright © 2024 World Federation of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Lithium metal batteries (LMBs) with LiNi 0.8 Co 0.1 Mn 0.1 O 2 (NCM811) cathodes have garnered significant interest as next-generation energy storage devices due to their high energy density. However, the instability of their electrode/electrolyte interfaces in regular carbonate electrolytes (RCEs) results in a rapid capacity decay. To address this, a colloid electrolyte consisting of Li 3 P nanoparticles uniformly dispersed in the RCE is developed by a one-step synthesis. This design concurrently creates stable cathode electrolyte interphase (CEI) and solid electrolyte interphase (SEI) on both electrode surfaces. The cathode interface derived from this colloid electrolyte significantly facilitates the decomposition of Li salts (LiPF 6 and LiDFOB) on the cathode surface by weakening the P-F and B-F bonds. This in situ formed P/LiF-rich CEI effectively protects the NCM811 cathode from side reactions. Furthermore, the Li 3 P embedded in the SEI optimizes and homogenizes the Li-ion transport, enabling dendrite-free Li deposition. Compared to the RCE, the designed colloid electrolyte enables robust cathode and anode interfaces in NCM811||Li full cells, minimizing gas and dendrite formation, and delivering a superior capacity retention of 82% over 120 cycles at a 4.7 V cutoff voltage. This approach offers different insights into electrolyte regulation and explores alternative electrolyte shapes and formulations.

Blood vessels and nerve fibers are distributed throughout the skeletal tissue, which enhance the development and function of each other and have an irreplaceable role in bone formation and remodeling. Despite significant progress in bone tissue engineering, the inadequacy of nerve-vascular network reconstruction remains a major limitation. This is partly due to the difficulty of integrating and regulating multiple tissue types with artificial materials. Thus, understanding the anatomy and underlying coupling mechanisms of blood vessels and nerve fibers within bone to further develop neuro-vascularized bone implant biomaterials is an extremely critical aspect in the field of bone regeneration. Hydrogels have good biocompatibility, controllable mechanical characteristics, and osteoconductive and osteoinductive properties, making them important candidates for research related to neuro-vascularized bone regeneration. This review reports the classification and physicochemical properties of hydrogels, with a focus on the application advantages and status of hydrogels for bone regeneration. The authors also highlight the effect of neurovascular coupling on bone repair and regeneration and the necessity of achieving neuro-vascularized bone regeneration. Finally, the recent progress and design strategies of hydrogel-based biomaterials for neuro-vascularized bone regeneration are discussed., (© 2024 Wiley‐VCH GmbH.)

Mesoporous bioactive glasses (MBGs), which belong to the category of modern porous nanomaterials, have garnered significant attention due to their impressive biological activities, appealing physicochemical properties, and desirable morphological features. They hold immense potential for utilization in diverse fields, including adsorption, separation, catalysis, bioengineering, and medicine. Despite possessing interior porous structures, excellent morphological characteristics, and superior biocompatibility, primitive MBGs face challenges related to weak encapsulation efficiency, drug loading, and mechanical strength when applied in biomedical fields. It is important to note that the advantageous attributes of MBGs can be effectively preserved by incorporating supramolecular assemblies, miscellaneous metal species, and their conjugates into the material surfaces or intrinsic mesoporous networks. The innovative advancements in these modified colloidal inorganic nanocarriers inspire researchers to explore novel applications, such as stimuli-responsive drug delivery, with exceptional in-vivo performances. In view of the above, we outline the fabrication process of calcium-silicon-phosphorus based MBGs, followed by discussions on their significant progress in various engineered strategies involving surface functionalization, nanostructures, and network modification. Furthermore, we emphasize the recent advancements in the textural and physicochemical properties of MBGs, along with their theranostic potentials in multiple cancerous and non-cancerous diseases. Lastly, we recapitulate compelling viewpoints, with specific considerations given from bench to bedside., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Engineering mesoporous bioactive glasses for emerging stimuli-responsive drug delivery and theranostic applications”., (© 2024 The Authors.)

Periodontitis is a chronic infectious disease caused by bacterial irritation. As an essential component of the host immunity, macrophages are highly plastic and play a crucial role in inflammatory response. An appropriate and timely transition from proinflammatory (M1) to anti-inflammatory (M2) macrophages is indispensable for treating periodontitis. As M2 macrophage-derived exosomes (M2-exos) can actively target inflammatory sites and modulate immune microenvironments, M2-exos can effectively treat periodontitis. Excessive endoplasmic reticulum stress (ER stress) and unfolded protein response (UPR) are highly destructive pathological characteristics during inflammatory periodontal bone loss. Although melatonin has antioxidant and anti-inflammatory effects, studies focusing on melatonin ER stress modulation remain limited. This study fabricates engineered M2-exos loading with melatonin (Mel@M2-exos) for treating periodontitis. As a result, M2-exos drive an appropriate and timely macrophage reprogramming from M1 to M2 type, which resolves chronic inflammation and accelerated periodontal healing. Melatonin released from Mel@M2-exos rescues the osteogenic and cementogenic differentiation capacity in inflammatory human periodontal ligament cells (hPDLCs) by reducing excessive ER stress and UPR. Injectable gelatin methacryloyl (GelMA) hydrogels with sustained-release Mel@M2-exos accelerate periodontal bone regeneration in rats with ligation-induced periodontitis. Taken together, melatonin engineering M2 macrophage-derived exosomes are promising candidates for inflammatory periodontal tissue regeneration., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Purpose: Our aim was to investigate the normal reference value and to establish an estimation formulae for renal structural parameters (RSPs) based on large-sample CT data of Chinese children, which can provide a data reference for the clinical assessment of kidney development and diseases in Chinese children., Materials and Methods: A total of 438 children aged 0-17 years with normal renal CT images and basic indices were continuously collected. The bilateral RSP, including renal length (RL), renal width (RW), renal thickness (RT), renal volume (RV), renal cortical thickness (RCT), renal artery diameter (RAD) and renal CT value, were measured. Kendall's rank correlation was used to analyze the correlation between RSP and sex. Pearson's correlation was used to analyze the correlation between RSP and age, height and weight. Differences in the RSP of bilateral kidneys were analyzed via a paired samples t-test. Multiple linear regression was used to analyze the multivariate relationships between RSP and basic indices and establish the estimation formula of RSP., Results: The RSP of normal kidneys showed a dynamic increasing trend with age, except for the CT values. The reference value ranges (95% confidence interval) of normal RSP for each age group were determined. Pearson correlation analysis demonstrated strong correlations between RSP (RL, RW, RT, RV, RCT and, RAD) and basic indices (age, height and, weight), with height exhibiting the greatest correlation coefficient, followed by age or weight. Kendall's analysis showed that none of the RSPs were correlated with sex. The RL, RW, RV and RAD of the left kidney were larger than those of the right kidney, and the RT and RCT of the right kidney exhibited opposite results. Multiple linear regression analysis demonstrated a significant linear relationship between the RSP (RL, RW, RT, RV and, RCT) and the variables of the basic indices. The estimation formulae for calculating the RSP were established., Conclusion: This is the first Chinese study to report of the trends, normal reference values and estimation formulae of normal RSP based on large-sample CT data. These results can provide data references for assessing adequate kidney growth or disease damage in Chinese children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Qin, Liu, Ni, Huang, Tian, He, Cai and Li.)

Objective: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common inherited mitochondrial disorders. Due to the high clinical and genetic heterogeneity of MELAS, it is still a major challenge for clinicians to accurately diagnose the disease at an early stage. Herein, we evaluated the neuroimaging findings of MELAS with an m.3243A>G mutation in MT-TL1 and analyzed the possible underlying pathogenesis of stroke-like episodes., Materials and Methods: Fifty-nine imaging studies in 24 patients who had a confirmed genetic diagnosis of m.3243A>G ( MT-TL1; tRNA Leu ) associated with MELAS were reviewed in our case series. The anatomic location, morphological features, signal/intensity characteristics and temporal evolution of lesions were analyzed on magnetic resonance imaging (MRI), and computed tomography (CT) images. The supplying vessels and metabolite content of the lesions were also evaluated by using MR angiography (MRA)/CT angiography (CTA), and MR spectroscopy (MRS), respectively., Results: The lesions were most commonly located in the posterior brain, with 37 (37/59, 63%) in the occipital lobe, 32 (32/59, 54%) in the parietal lobe, and 30 (30/59, 51%) in the temporal lobe. The signal characteristics of the lesions varied and evolved over time. Bilateral basal ganglia calcifications were found in 6 of 9 (67%) patients who underwent CT. Cerebral and cerebellar atrophy were found in 38/59 (64%) and 40/59 (68%) patients, respectively. Lesion polymorphism was found in 37/59 (63%) studies. MRS showed elevated lactate doublet peaks in 9/10 (90%) cases. MRA or CTA revealed that the lesion-related arteries were slightly dilated compared with those of the contralateral side in 4 of 6 (67%) cases., Conclusion: The imaging features of MELAS vary depending on the disease stage. Polymorphic lesions in a single imaging examination should be considered a diagnostic clue for MELAS. Stroke-like episodes may be involved in a complex pathogenetic process, including mitochondrial angiopathy, mitochondrial cytopathy, and neuronal excitotoxicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zheng, Zhang, Tian, Liu, He, Wang, Ding, Guo and Cai.)

Background: Fibroblastic reticular cells (FRCs) are a type of stromal cells located in the T zone in secondary lymphoid organs. Previous studies showed that FRCs possess the potential to promote myeloid differentiation. We aim to investigate whether FRCs in lymph nodes (LNs) could induce tolerogenic macrophage generation and further influence T-cell immunity at an early stage of allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: LNs were assayed to confirm the existence of proliferating macrophages after allo-HSCT. Ex vivo-expanded FRCs and bone marrow cells were cocultured to verify the generation of macrophages. Real-time quantitative PCR and ELISA assays were performed to observe the cytokines expressed by FRC. Transcriptome sequencing was performed to compare the difference between FRC-induced macrophages (FMs) and conventional macrophages. Mixed lymphocyte reaction and the utilization of FMs in acute graft-versus-host disease (aGVHD) mice were used to test the inhibitory function of FMs in T-cell immunity in vitro and in vivo., Results: We found a large number of proliferating macrophages near FRCs in LNs with tolerogenic phenotype under allo-HSCT conditions. Neutralizing anti-macrophage colony-stimulating factor receptor antibody abolished FMs generation in vitro. Phenotypic analysis and transcriptome sequencing suggested FMs possessed immunoinhibitory function. Mixed lymphocyte reaction proved that FMs could inhibit T-cell activation and differentiation toward Th1/Tc1 cells. Injection of FMs in aGVHD mice effectively attenuated aGVHD severity and mortality., Conclusions: This study has revealed a novel mechanism of immune regulation through the generation of FRC-induced tolerogenic macrophages in LNs at an early stage of allo-HSCT., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: We induced the AD-like rat models injected by AlCl 3 and D-galactose, to explore the effects of an oral treatment of A. muciniphila on AD-like rats with periodontitis and its possible mechanism., Main Methods: We used Morris water maze test and micro-CT to assess the cognitive impairment and bone loss; Aβ1-42 deposition was tested by IHC; Serum LPS level and TG, HDL-C and AST/ALT levels were detected by LAL Test and biochemical tests; The gut microbiota was analyzed by 16S rRNA gene sequence., Key Findings: We found that A. muciniphila could alleviate AD-like rats' cognitive impairment and mitigate ligature-induced periodontitis. Furthermore, A. muciniphila reduced Aβ1-42 deposition in the cortex and regions of the rats' brain, and altered TG, HDL-C and AST/ALT levels but had little ability to change circulating LPS level and cross the blood-brain barrier. Notably, A. muciniphila treatment could improve the abundance of some short chain fatty acid (SCFA)-producing or neurotransmitter-producing gut microbiome such as Blautia, Staphylococcus and Lactococcus, while the abundance of pathogenic Aerococcus and Streptococcus, which were associated inflammation, were decreased., Significance: Our findings suggested that A. muciniphila has a remissive effect on AD-like pathologies, potentially by regulating gut-brain axis through altering composition and function of gut microbial community or moderating peripheral circulation metabolism., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: Familial encephalopathy with neuroserpin inclusion bodies (FENIB), a rare neurogenetic disease, is characterized by progressive cognitive decline and myoclonus and caused by pathogenic variants of the SERPINI1 gene that lead to the formation of neuroserpin inclusion bodies., Methods: We described the case of an Asian patient with FENIB associated with a pathogenic variant of SERPINI1 and summarized and analyzed the clinical characteristics of the case. In addition, we conducted a literature review of previously reported patients with this disease., Results: The patient, a 16-year-old Chinese girl, presented with progressive cognitive decline and myoclonus that had started at the age of 11 years. The girl was found to carry a de novo heterozygous c.1175G>A (p.G392E) variant of the SERPINI1 gene, which is a pathogenic variant according to the guidelines of the American College of Medical Genetics and Genomics. She had responded poorly to antiseizure medications (ASMs). At the last follow-up, her myoclonus was still out of control, and her self-care ability was poor. Our literature review revealed that 13 similar cases (including 9 cases in male patients) have been reported so far, in which six pathogenetic variations in SERPINI1, including G392E, were responsible for FENIB. All the patients presented with myoclonus, and 12 patients had experienced at least one other type of seizure. Further, as observed in our case, 9 out of 12 patients did not respond to ASMs. Progressive cognitive decline was observed in all the patients, and 10 out of 13 patients had dyskinesia. The median age of disease onset was 21 years, and the median age at the time of death was 33 years. Further, 9 out of 13 patients showed signs of cerebral and/or cerebellar atrophy. Finally, neuroserpin inclusion bodies were identified in six patients who underwent brain biopsy or autopsy., Conclusions: Pathogenic variants of SERPINI1 should be suspected in children with progressive cognitive decline and myoclonus, especially in those with progressive myoclonus epilepsy. Further, gene detection and brain biopsy are important means for the diagnosis of FENIB., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore whether Fusobacterium nucleatum could lead to behavioral and pathological changes in Alzheimer's disease (AD)-like model rat and whether they could affect the gut microbiota., Methods: The cognitive ability and alveolar bone loss of Sprague-Dawley (SD) rats were tested by Morris water maze and Micro-CT, respectively. HE staining and immunohistochemistry were used to analyze the pathological changes and Aβ1-42 in brains. Western blot was applied to detect the expression of p-Tau 181 in the brain. Limulus amebocyte lysate assay and PCR were performed to determine serum LPS level and whether F. nucleatum accessed the brain, respectively. The gut microbiota was analyzed by the 16S rRNA gene sequence., Results: Oral infection with F. nucleatum could induce increased alveolar bone loss and learning impairment in AD-like rats. Additionally, F. nucleatum exposure increased the Aβ1-42 expression by about one-fourth ( P < 0.05), p-Tau181 by about one-third ( P < 0.05), and serum LPS ( P < 0.05) in AD-like rats. Moreover, F. nucleatum could change the gut microflora composition in AD-like rats, accompanied by a significant increase in the abundance of Streptococcus and Prevotella ., Conclusion: Oral infection with F. nucleatum could contribute to abnormalities in cognitive ability and pathological change in the brain of AD-like rats, which may be related to abnormal gut microbiota composition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Diao, Zhao, Zhang, He, Huang and Li.)

Background: Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder characterized by epilepsy and structural abnormalities of the brain. Little research has been done to explore the relationship between the tuber brain proportion (TBP) and epilepsy. We investigated several quantitative cerebral lesions including TBP on magnetic resonance imaging (MRI) and their impact on the onset age, seizure mode, and antiseizure treatment effectiveness of epilepsy in children with TSC., Methods: We reviewed the clinical characteristics and MRI information of 44 children with TSC who had experienced epileptic seizures. Supratentorial tubers were quantitatively manually measured to calculate the TBP. The numbers of cortical/subcortical cyst-like tubers, diffuse lesions, subependymal nodules, and subependymal giant cell astrocytomas were also evaluated., Results: Twelve children (27.3%) had experienced infantile spasms, thirteen children (29.5%) had early-onset epilepsy, and twenty-seven patients (64.3%) had a significant reduction in the frequency of seizures after antiseizure treatments. The median TBP was 9.2%, and diffuse lesions (range: 0-2) and cortical cyst-like lesions (range: 0-17) were seen in seven and seventeen children, respectively. The values of TBP (P < 0.001), diffuse lesions (P < 0.001), and cortical cyst-like tubers (P < 0.001) were all associated with early-onset epilepsy. The values of TBP (P = 0.004) and cortical cyst-like tuber (P < 0.001) were associated with the occurrence of infantile spasms. The values of TBP (P = 0.01), diffuse lesions (P = 0.04), and cortical cyst-like tubers (P = 0.004) were negatively associated with the effectiveness of antiseizure treatments. There was no significant correlation between subcortical cyst-like tuber, subependymal nodule, subependymal giant cell astrocytoma, and epilepsy severity., Conclusions: Increasing abnormality of the cerebral hemispheres, as shown by quantitative MRI analysis including TBP, cortical cyst-like tubers, and diffuse lesions, is associated with measures of more severe epilepsy due to TSC. The values of TBP demonstrate strong significance for early-onset epilepsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Enterococcus faecalis (E. faecalis) is associated with persistent root canal infection because of its biofilm and various virulence factors. However, E. faecalis exhibits extensive drug resistance. d-Alanine (D-Ala) metabolism is essential for bacterial peptidoglycan biosynthesis. d-cycloserine (DCS), a second line drug used in the treatment of Mycobacterium tuberculosis infection, can inhibit two key enzymes in D-Ala metabolism: alanine racemase and d-alanine-d-alanine ligase. The aim of this study was to evaluate the effect of D-Ala metabolism on E. faecalis growth, cell wall integrity, biofilm formation and virulence gene expression by additional DCS with or without D-Ala. The results showed that DCS inhibited the planktonic growth and biofilm formation of E. faecalis in a dose-dependent manner. Both the minimum inhibitory concentration (MIC) and minimum biofilm inhibition concentration (MBIC) of DCS against E. faecalis were 200 μg/ml, whereas 50 μg/ml of DCS could inhibit planktonic growth and biofilm formation effectively. The addition of DCS also resulted in bacterial cell wall damage, biofilm surface roughness increase and biofilm adhesion force reduction. Moreover, the treatment of DCS downregulated the expression of asa1, esp, efaA, gelE, sprE, fsrB and ace genes. However, all of these inhibitory effects of DCS could be rescued by the addition of exogenous D-Ala. Meanwhile, DCS exhibited no toxicity to HGEs and HOKs. Therefore, D-Ala metabolic pathway in E. faecalis is a potential target for drug designing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The ability of Streptococcus mutans to survive and cause dental caries is dependent on its ability to metabolize various carbohydrates, accompanied by extracellular polysaccharide synthesis and biofilm formation. Here, the role of an rel competence-related regulator (RcrR) in the regulation of multiple sugar transportation and biofilm formation is reported. The deletion of the rcrR gene in S. mutans caused delayed growth, decreased biofilm formation ability, and affected the expression level of its multiple sugar transportation-related genes. Transcriptional profiling revealed 17 differentially expressed genes in the rcrR mutant. Five were downregulated and clustered with the sugar phosphotransferase (PTS) systems (mannitol- and trehalose-specific PTS systems). The conserved sites bound by the rcrR promoter were then determined by electrophoretic mobility shift assays (EMSAs) and DNase I footprinting assays. Furthermore, a potential binding motif in the promoters of the two PTS operons was predicted using MEME Suite 5.1.1. RcrR could bind to the promoter regions of the two operons in vitro , and the sugar transporter-related genes of the two operons were upregulated in an rcrR -overexpressing strain. In addition, when RcrR-binding sites were deleted, the growth rates and final yield of S. mutans were significantly decreased in tryptone-vitamin (TV) medium supplemented with different sugars, but not in absolute TV medium. These results revealed that RcrR acted as a transcription activator to regulate the two PTS systems, accompanied by multiple sugar transportation and biofilm formation. Collectively, these results indicate that RcrR is a critical transcription factor in S. mutans that regulates bacterial growth, biofilm formation, and multiple sugar transportation. IMPORTANCE The human oral cavity is a constantly changing environment. Tooth decay is a commonly prevalent chronic disease mainly caused by the cariogenic bacterium Streptococcus mutans. S. mutans is an oral pathogen that metabolizes various carbohydrates into extracellular polysaccharides (EPSs), biofilm, and tooth-destroying lactic acid. The host diet strongly influences the availability of multiple carbohydrates. Here, we showed that the RcrR transcription regulator plays a significant role in the regulation of biofilm formation and multiple sugar transportation. Further systematic evaluation of how RcrR regulates the transportation of various sugars and biofilm formation was also conducted. Notably, this study decrypts the physiological functions of RcrR as a potential target for the better prevention of dental caries.

Acute graft-versus-host disease (aGVHD) remains a significant and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the occurrence of aGVHD, allo-HSCT significantly increases the mortality rate compared with autologous hematopoietic stem cell transplantation (auto-HSCT). In this study, auto-HSCT and allo-HSCT aGVHD mouse models were built to detect the difference in CD4 + lymphocyte in different tissues based on ribonucleic acid sequencing (RNA-Seq) analysis. Clustering analysis, functional annotation, and pathway enrichment analysis were performed on differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to find hub genes. CD4 + T cells were activated by MLR and cytokine stimulation. Cells were sorted out by a flow cell sorter. The selected genes were verified by qRT-PCR, histology, and immunofluorescence staining. The GSE126518 GEO dataset was used to verify the hub genes. Enrichment analysis revealed four immune-related pathways that play an important role in aGVHD, including immunoregulatory interactions between a lymphoid and a nonlymphoid cell, chemokine receptors binding chemokines, cytokine and cytokine receptor interaction, and the chemokine signaling pathway. At the same time, with the PPI network, 11 novel hub genes that were most likely to participate in immunoregulation in aGVHD were identified, which were further validated by qRT-PCR and the GSE126518 dataset. Besides, the protein expression level of Cxcl7 was consistent with the sequencing results. In summary, this study revealed that immunoregulation-related DEGs and pathways played a vital role in the onset of aGVHD. These findings may provide some new clues for probing the pathogenesis and treatment of aGVHD., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Zhengyu Yu et al.)

Objective: The current study aimed to assess the antimicrobial activity of ursolic acid (UA) against multi-species biofilms formed by Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii, as well as to measure its biocompatibility., Methods: Crystal violet staining, CFU counting, CCK-8 assays and scanning electron microscopy (SEM) were applied to investigate the effect of UA on multi-species biofilms. UA's effect on exopolysaccharides (EPS) production was measured using confocal laser scanning microscopy (CLSM) and the anthrone-sulfuric acid method. Fluorescent in situ hybridization (FISH) was applied to visualize and quantify the microbial composition of multi-species biofilms. Quantitative real-time PCR (qRT-PCR) was used to measure the expression of virulence genes of S. mutans, S. sanguinis, and S. gordonii under UA treatment. Moreover, CCK-8 assays were performed to evaluate its cytotoxicity against human oral keratinocytes (HOKs) and human gingival epithelial cells (HGEs)., Results: The results showed that UA had significant antimicrobial activity against common oral streptococci. UA also reduced the EPS synthesis of oral streptococci and suppressed gtf genes' expression. In addition, UA reduced the proportion of S. mutans in multi-species biofilms. Besides, UA had low cytotoxicity against HOKs and HGEs., Conclusions: UA exhibited antibiofilm activity against oral pathogenic bacteria and had the potential to be used in dental caries treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Multi-marker tests hold promise for identifying symptomatic women at risk of imminent preterm delivery (PTD, <37 week's gestation). This study sought to determine the relationship of inflammatory mediators and metabolites in cervicovaginal fluid (CVF) with spontaneous PTD (sPTD) and delivery within 14 days of presentation with symptoms of preterm labour (PTL). CVF samples from 94 (preterm = 19, term = 75) singleton women with symptoms of PTL studied between 19+0-36+6 weeks' gestation were analysed for cytokines/chemokines by multiplexed bead-based immunoassay, while metabolites were quantified by enzyme-based spectrophotometry in a subset of 61 women (preterm = 16, term = 45). Prevalence of targeted vaginal bacterial species was determined for 70 women (preterm = 14, term = 66) by PCR. Overall, 10 women delivered within 14 days of sampling. Predictive capacities of individual biomarkers and cytokine-metabolite combinations for sPTD and delivery within 14 days of sampling were analysed by logistic regression models and area under the receiver operating characteristic curve. Fusobacterium sp., Mubiluncus mulieris and Mycoplasma hominis were detected in more preterm-delivered than term women (P<0.0001), while, M. curtisii was found in more term-delivered than preterm women (P<0.0001). RANTES (0.91, 0.65-1.0), IL-6 (0.79, 0.67-0.88), and Acetate/Glutamate ratio (0.74, 0.61-0.85) were associated with delivery within 14 days of sampling (AUC, 95% CI). There were significant correlations between cytokines and metabolites, and several cytokine-metabolite combinations were associated with sPTD or delivery within 14 days of sampling (e.g. L/D-lactate ratio+Acetate/Glutamate ratio+IL-6: 0.84, 0.67-0.94). Symptomatic women destined to deliver preterm and within 14 days of sampling express significantly higher pro-inflammatory mediators at mid to late gestation. In this cohort, IL-6, Acetate/Glutamate ratio and RANTES were associated with delivery within 14 days of sampling, consistent with their roles in modulating infection-inflammation-associated preterm labour in women presenting with symptoms of preterm birth. Replication of these observations in larger cohorts of women could show potential clinical utility., Competing Interests: The authors have declared that no competing interests exist.

Magnetic resonance imaging (MRI) based on the ferritin heavy chain 1 (FTH1) reporter gene has been used to trace stem cells. However, whether FTH1 expression is affected by stem cell differentiation or whether cell differentiation is affected by reporter gene expression remains unclear. Here, we explore the relationship between FTH1 expression and neural differentiation in the differentiation of mesenchymal stem cells (MSCs) carrying FTH1 into neuron-like cells and investigate the feasibility of using FTH1 as an MRI reporter gene to detect neurally differentiated cells. By inducing cell differentiation with all-trans retinoic acid and a modified neuronal medium, MSCs and MSCs-FTH1 were successfully differentiated into neuron-like cells (Neurons and Neurons-FTH1), and the neural differentiation rates were (91.56±7.89)% and (92.23±7.64)%, respectively. Neuron-specific markers, including nestin, neuron-specific enolase, and microtubule-associated protein-2, were significantly expressed in Neurons-FTH1 and Neurons without noticeable differences. On the other hand, FTH1 was significantly expressed in MSCs-FTH1 and Neurons-FTH1 cells, and the expression levels were not significantly different. The R2 value was significantly increased in MSCs-FTH1 and Neurons-FTH1 cells, which was consistent with the findings of Prussian blue staining, transmission electron microscopy, and intracellular iron measurements. These results suggest that FTH1 gene expression did not affect MSC differentiation into neurons and was not affected by neural differentiation. Thus, MRI reporter gene imaging based on FTH1 can be used for the detection of neurally differentiated cells from MSCs.

Although mesenchymal stem cells (MSCs) have been demonstrated to possess a tumor‑homing feature, their tropism to liver tumors has not been delineated in a visible manner. The aim of the present study was to evaluate the tumor‑homing capacity of MSCs and to investigate the spatial and temporal distributions of MSCs in liver tumors using magnetic resonance imaging (MRI). MSCs were colabeled with superparamagnetic iron oxide (SPIO) particles and 4',6‑diamidino‑2‑phenylindole (DAPI), and then transplanted into rabbits with VX2 liver tumors through intravenous injections. The rabbits were subjected to MRI before and at 3, 7 and 14 days after cell transplantation using a clinical 1.5‑T MRI system. Immediately after the MRI examination, histological analyses were performed using fluorescence and Prussian blue staining. At 3 days after injection with labeled MSCs, heterogeneous hypointensity was detected on the MRI images of the tumor. At 7 days after transplantation, the tumor exhibited anisointense MRI signal, whereas a hypointense ring was detected at the border of the tumor. At 14 days after transplantation, the MRI signal recovered the hyperintensity. As demonstrated in the histological analyses, the distribution of the iron particles visualized with Prussian blue staining was consistent with the DAPI‑stained bright fluorescent nuclei, and the particles corresponded to the hypointense region on the MR images. Thus, systemically administered MSCs could localize to liver tumors with high specificity and possessed a migration feature with active tumor growth. These results demonstrated that the targeting and distribution of the magnetically labeled stem cells in the tumor could be tracked for 7 days in vivo using a clinical 1.5‑T MRI scanner.

As a promising magnetic resonance imaging (MRI) reporter, ferritin has been used to track cells in vivo; however, its continuous overexpression can be cytotoxic, which restricts its application. In this study, we aimed to develop a switch to turn this genetic reporter "on" or "off" while monitoring cell grafts via MRI. To accomplish this, we genetically modified the ferritin heavy chain (FTH1) with a Tet-On switch and assessed the expression of FTH1 in transduced neuroblastoma cells (SK-N-SH) in vitro and in xenografted tumors in vivo. We found that FTH1 expression induced by doxycycline (Dox) in SK-N-SH-FTH1 cells depended on treatment dose and duration. We successfully detected T2-weighted MRI contrast in cell grafts after switching "on" the reporter gene using Dox, and this contrast disappeared when we switched it "off". The genetic reporter FTH1 can thus be switched "on" or "off" throughout longitudinal monitoring of cell grafts, limiting expression to when MRI contrast is needed. The controllable imaging system we have developed minimizes risks from constitutive reporter gene overexpression and facilitates tumor cell monitoring in vitro and in vivo.

Introduction: Despite the strong appeal of ferritin as a magnetic resonance imaging (MRI) reporter for stem cell research, no attempts have been made to apply this genetic imaging reporter in stem cells in an inducible manner, which is important for minimizing the potential risk related to the constitutive expression of an imaging reporter. The aim of the present study was to develop an inducible genetic MRI reporter system that enables the production of intracellular MRI contrast as needed., Methods: Ferritin heavy chain (FTH1) was genetically modified by adding a Tet-On switch. A C3H10T1/2 cell line carrying Tet-FTH1 (C3H10T1/2-FTH1) was established via lentiviral transduction. The dose- and time-dependent expression of FTH1 in C3H10T1/2 cells was assessed by western blot and immunofluorescence staining. The induced "ON" and non-induced "OFF" expressions of FTH1 were detected using a 3.0 T MRI scanner. Iron accumulation in cells was analyzed by Prussian blue staining and transmission electron microscopy (TEM)., Results: The expression of FTH1 was both dose- and time-dependently induced, and FTH1 expression peaked in response to induction with doxycycline (Dox) at 0.2 μg/ml for 72 h. The induced expression of FTH1 resulted in a significant increase in the transverse relaxation rate of C3H10T1/2-FTH1 cells following iron supplementation. Prussian blue staining and TEM revealed extensive iron accumulation in C3H10T1/2-FTH1 cells in the presence of Dox., Conclusions: Cellular MRI contrast can be produced as needed via the expression of FTH1 under the control of a Tet-On switch. This finding could lay the groundwork for the use of FTH1 to track stem cells in vivo in an inducible manner.

Osteosclerotic metaphyseal dysplasia (OMD) is a very rare sclerosing bone disorder. To date, four cases have been documented in three reports. Here, we present the case of a 12-year-old girl with a history of recurrent respiratory infections, hypotonia, developmental delay, genu valgum, and hepatosplenomegaly. Radiographs revealed profound, ivory-white sclerosis of the metaphyses and epiphyses of the long bones in both the upper and lower extremities. Sclerosis also affected the ends or margins of the flat bones, including the mandible, clavicles, scapulae, ribs, iliac crests, ischia, pubic bones, talus, calcaneus, and some vertebrae, to varying degrees. Based on the clinical, radiographic, and laboratory findings, a diagnosis of OMD was made. Our patient is the fifth case of OMD reported in the international literature and shares clinical and radiological similarities with four other reported cases of OMD. However, the extensive interstitial pulmonary lesions observed on computed tomography images in the present case have not been previously documented. This pulmonary disorder, which may be associated with OMD, should be evaluated in subsequently encountered cases.