Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Objective To explore growth pattern of neo-aortic root as well as development of neo-aortic regurgitation after arterial switch operation (ASO) for Taussig-Bing anomaly. Methods From 2002 to 2017, the patients who received ASO, and were discharged alive from Shanghai Children’s Medical Center and followed up for more than 3 years were retrospectively involved in this study. Results A total of 127 patients were enrolled. There were 98 (77.2%) males, the median age at ASO was 73.0 d and the average weight was 4.7 kg. Forty-five (35.4%) children were complicated with mild or mild-to-moderate pulmonary insufficiency (PI) before ASO. The average follow-up time was 7.0 years. During the follow-up, 14 (11.0%) children presented moderate or greater neo-aortic regurgitation (neo-AR). The diameter of neo-aortic annulus and sinus of Valsalva was beyond normal range during the entire follow-up. The average diameter of neo-aortic annulus was 18.0 mm at 5 years and 20.5 mm at 10 years. The average diameter of sinus of Valsalva was 25.9 mm at 5 years and 31.1 mm at 10 years. Neo-AR continued to develop over time. The diameter of children who developed moderate or greater neo-AR was constantly larger than that of children who did not (χ2=18.3, P<0.001). Preoperative mild or mild-to-moderate PI was an independent risk factor for the development of moderate or greater neo-AR during mid-to-long term follow-up (c-HR=3.46, P=0.03). Conclusion The diameters of neo-aortic annulus and sinus of Valsalva of Taussig-Bing children who receive ASO repair continue to expand without normalization. The dilation of annulus correlates with the development of neo-AR. PI before ASO repair increases the risk of neo-AR development.

FOXM1(forkhead box M1)is an important member of the FOX transcription factor family and plays a critical role in driving the progression of multiple malignancies through its transcriptional regulatory functions.Moreover,the overexpression of FOXM1 is associated with poor prognosis in many types of cancer,as it regulates a variety of biological processes such as gene expression,cell proliferation,invasion,metastasis,and apoptosis.Presently,aberrant metabolic reprogramming has been considered as the major characteristic of cancer development,determining the survival,growth,and proliferation of tumor cells.Accumulating evidence suggests that FOXM1 serves as a"bridge"between metabolism and tumorigenesis.This review aims to provide a comprehensive summary of the research progress in the relationship between FOXM1 and tumor cell metabolism,offering theoretical insights for the development of novel anti-cancer drugs targeting FOXM1.

Olfactory bulb is a critical component in encoding and processing olfactory signals, characterized by its intricate neural projections and networks dedicated to this function. It has been found that descending neural projections from the olfactory cortex and other advanced brain regions can modulate the excitability of olfactory bulb output neurons in the olfactory bulb, either directly or indirectly, which can further influence olfactory discrimination, learning, and other abilities. In recent years, advancements in optogenetic technology have facilitated extensive application of neuron manipulation for studying neural circuits, thereby greatly accelerating research into olfactory mechanisms. This review summarizes the latest research progress on the regulatory effects of neural projections from the olfactory cortex, basal forebrain, raphe nucleus, and locus coeruleus on olfactory bulb function. Furthermore, the important role that photogenetic technology plays in olfactory mechanism research is evaluated. Finally, the existing problems and future development trends in current research are preliminarily proposed and explained. This review aims to provide new insights into the mechanisms underlying olfactory neural regulation as well as applications of optogenetic technology, which are crucial for advancing the research on olfactory mechanism and the application of optogenetic technology.
Olfactory Bulb/physiology* ; Optogenetics/methods* ; Animals ; Humans ; Olfactory Pathways/physiology* ; Olfactory Cortex/physiology* ; Smell/physiology*

Objective    To explore the effect of LeCompte maneuver on in-hospital mortality and mid-to-long term reintervention after single-stage arterial switch operation in children with side-by-side Taussig-Bing anomaly. Methods     Clinical data of patients diagnosed with side-by-side Taussig-Bing anomaly and undergoing single-stage arterial switch operation in Shanghai Children’s Medical Center from 2006 to 2017 were retrospectively analyzed. Patients were divided into two groups based on whether LeCompte maneuver was performed: a LeCompte maneuver group and a non LeCompte maneuver group. The clinical data of two groups were compared. Results    Finally 92 patients were collected. LeCompte maneuver was performed in 32 out of 92 patients with a median age of 65.0 days and an average weight of 4.3 kg, among whom 24 (75.0%) were male. Fifteen (46.9%) patients received concomitant aortic arch repair while 12 (37.5%) patients were associated with coronary artery malformation. LeCompte maneuver was not performed in 60 patients with a median age of 81.0 days and an average weight of 4.8 kg, among whom 45 (75.0%) were male. Twenty-two (36.7%) patients received concomitant aortic arch repair while 35 (58.3%) patients were associated with coronary artery malformation. The average cardiopulmonary bypass duration of the LeCompte maneuver group showed no statistical difference from the non LeCompte maneuver group (179.0±60.0 min vs. 203.0±74.0 min, P=0.093). The in-hospital mortality of the two groups were 6 (18.8%) and 7 (11.7%), respectively, which also showed no statistical difference (P=0.364). The median follow-up period was 4.1 (1.6, 7.5) years for 79 patients with 8 lost to follow-up, and no death was observed. Kaplan-Meier curve and log-rank test showed no statistical difference in overall mid-to-long term reintervention rate (P=0.850) as well as right ventricular outflow tract and pulmonary artery reintervention rate (P=0.240) with or without LeCompte maneuver. Conclusion    Whether or not to perform LeCompte maneuver shows no statistical impact on in-hospital mortality and mid-to-long term reintervention rate of single-stage arterial switch operation for side-by-side Taussig-Bing anomaly.

Objective: This study aimed to evaluate the zygomaticotemporal suture (ZTS) maturation, analyze the age distribution patterns of ZTS maturation stages, and investigate the relationship between ZTS and cervical vertebral maturation (CVM). Methods: A total of 261 patients who underwent cone-beam computed tomography (112 males, mean age, 13.1 ± 3.3 years; 149 females, mean age, 13.7 ± 3.1 years) were examined to evaluate the ZTS stages. The ZTS stages were defined based on a modified method from previous studies on zygomaticomaxillary sutures. Differences between groups and correlations between indicators were analyzed using the Spearman correlation test, intraclass coefficient of correlation (ICC), one-way analysis of variance and rank sum test.Statistical significance was set at p < 0.05. The diagnostic value of CVM stages in identifying ZTS maturation stages was evaluated using positive likelihood ratios (LRs). Results: A positive relationship was found between the ZTS and CVM stage (r = 0.747, ICC = 0.621, p < 0.01) and between the ZTS stage and chronological age (r = 0.727, ICC = 0.330, p < 0.01). Positive LRs > 10 were found for several cervical stages (CSs), including CS1 and CS2 for the diagnosis of stage B, CS1 to CS3 for the diagnosis of stages B and C, and CS6 for the diagnosis of stages D and E. Conclusions The ZTS maturation stage may be more relevant to the CVM stage than to the chronological age. The CVM stages can be good indicators for clinical decisions regarding maxillary protraction, except for CS4 and CS5.

Organic acids are organic compounds that can be synthesized using biological systems. They often contain one or more low molecular weight acidic groups, such as carboxyl group and sulphonic group. Organic acids are widely used in food, agriculture, medicine, bio-based materials industry and other fields. Yeast has unique advantages of biosafety, strong stress resistance, wide substrate spectrum, convenient genetic transformation, and mature large-scale culture technology. Therefore, it is appealing to produce organic acids by yeast. However, challenges such as low concentration, many by-products and low fermentation efficiency still exist. With the development of yeast metabolic engineering and synthetic biology technology, rapid progress has been made in this field recently. Here we summarize the progress of biosynthesis of 11 organic acids by yeast. These organic acids include bulk carboxylic acids and high-value organic acids that can be produced naturally or heterologously. Finally, future prospects in this field were proposed.
Saccharomyces cerevisiae/metabolism* ; Organic Chemicals ; Carboxylic Acids/metabolism* ; Metabolic Engineering ; Fermentation ; Acids

Hepatic ischemia/reperfusion injury (HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI. Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16S rRNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening (ZT12, 20:00) when compared with the morning (ZT0, 08:00); however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite 3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro. This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase (HDAC) inhibition in macrophages.