Carotenoid biosynthesis genes LcLCYB, LcLCYE, and LcBCH from wolfberry confer increased carotenoid content and improved salt tolerance in tobacco.

Carotenoids play essential roles in plant growth and development and provide plants with a tolerance to a series of abiotic stresses. In this study, the function and biological significance of lycopene ß-cyclase, lycopene ε-cyclase, and ß-carotene hydroxylase, which are responsible for the modification of the tetraterpene skeleton procedure, were isolated from Lycium chinense and analyzed. The overexpression of lycopene ß-cyclase, lycopene ε-cyclase, and ß-carotene hydroxylase promoted the accumulation of total carotenoids and photosynthesis enhancement, reactive oxygen species scavenging activity, and proline content of tobacco seedlings after exposure to the salt stress. Furthermore, the expression of the carotenoid biosynthesis genes and stress-related genes (ascorbate peroxidase, catalase, peroxidase, superoxide dismutase, and pyrroline-5-carboxylate reductase) were detected and showed increased gene expression level, which were strongly associated with the carotenoid content and reactive oxygen species scavenging activity. After exposure to salt stress, the endogenous abscisic acid content was significantly increased and much higher than those in control plants. This research contributes to the development of new breeding aimed at obtaining stronger salt tolerance plants with increased total carotenoids and vitamin A content.

Rutin prevents EqHV-8 induced infection and oxidative stress via Nrf2/HO-1 signaling pathway.

Introduction: The Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway has been extensively studied for its role in regulating antioxidant and antiviral responses. The Equid herpesvirus type 8 (EqHV-8) poses a significant threat to the equine industry, primarily manifesting as respiratory disease, abortions, and neurological disorders in horses and donkeys. Oxidative stress is considered a key factor associated with pathogenesis of EqHV-8 infection. Unfortunately, there is currently a dearth of therapeutic interventions available for the effective control of EqHV-8. Rutin has been well documented for its antioxidant and antiviral potential. In current study we focused on the evaluation of Rutin as a potential therapeutic agent against EqHV-8 infection. Methods: For this purpose, we encompassed both in-vitro and in-vivo investigations to assess the effectiveness of Rutin in combatting EqHV-8 infection. Results and Discussion: The results obtained from in vitro experiments demonstrated that Rutin exerted a pronounced inhibitory effect on EqHV-8 at multiple stages of the viral life cycle. Through meticulous experimentation, we elucidated that Rutin's antiviral action against EqHV-8 is intricately linked to the Nrf2/HO-1 signaling pathway-mediated antioxidant response. Activation of this pathway by Rutin was found to significantly impede EqHV-8 replication, thereby diminishing the viral load. This mechanistic insight not only enhances our understanding of the antiviral potential of Rutin but also highlights the significance of antioxidant stress responses in combating EqHV-8 infection. To complement our in vitro findings, we conducted in vivo studies employing a mouse model. These experiments revealed that Rutin administration resulted in a substantial reduction in EqHV-8 infection within the lungs of the mice, underscoring the compound's therapeutic promise in vivo. Conclusion: In summation, our finding showed that Rutin holds promise as a novel and effective therapeutic agent for the prevention and control of EqHV-8 infections.

ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. METHODS: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). RESULTS: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. CONCLUSIONS: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.

Induction of Peroxiredoxin 1 by Hypoxia Promotes Cellular Autophagy and Cell Proliferation in Oral Leukoplakia via HIF-1α/BNIP3 Pathway.

Hypoxia is a key trigger in the transformation of oral leukoplakia into oral cancer. However, it is still too early to determine the role of hypoxia in the development of oral leukoplakia. Prx1, an antioxidant protein, upregulated by hypoxia, regulates cellular autophagy in leukoplakia. This study aimed to understand the mechanisms by which hypoxia induces Prx1 expression during autophagy in oral leukoplakia. We used an experimental model of tongue epithelial hyperplasia induced by 4-nitroquinoline-1-oxide (4NQO) and dysplastic oral keratinocytes. Prx1 knockdown DOK cells, Leuk-1 cells and control cells were harvested, and cell proliferation was assayed using the Cell Counting Kit-8. Several hypoxia and autophagy-related proteins were examined using quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and western blotting in cells and mouse tongue tissues. In addition, the ultrastructure of the cells was observed by transmission electron microscopy. Hypoxia induces cell proliferation, autophagic vesicles and the expression of Prx1, BNIP3, LC3II/I and Beclin-1 in DOK and Leuk-1 cells. However, these effects were all attenuated by Prx1 knockdown. Histologically, 4NQO induced epithelial hyperplasia in the tongue mucosa. The expression of proliferation marker PCNA, autophagy-related proteins LC3B and Beclin-1, as well as HIF-1α/BNIP3 was significantly lower in the tongue tissues of Prx1flox/flox:Cre+ mice compared with Prx1flox/flox mice. In Prx1flox/flox:Cre+ mice, an increased expression of HIF-1α/BNIP3, LC3B and Beclin-1 was detected in epithelial hyperplasia tongue tissues compared to normal tissues. The current study suggests that Prx1 may promotes cell proliferation and autophagy in oral leukoplakia cells via the HIF-1α/BNIP3 pathway.

Hydrogen gas inhalation ameliorates LPS-induced BPD by inhibiting inflammation via regulating the TLR4-NFκB-IL6/NLRP3 signaling pathway in the placenta.

INTRODUCTION: Hydrogen (H2) is regarded as a novel therapeutic agent against several diseases owing to its inherent biosafety. Bronchopulmonary dysplasia (BPD) has been widely considered among adverse pregnancy outcomes, without effective treatment. Placenta plays a role in defense, synthesis, and immunity, which provides a new perspective for the treatment of BPD. This study aimed to investigate if H2 reduced the placental inflammation to protect the neonatal rat against BPD damage and potential mechanisms. METHODS: We induced neonatal BPD model by injecting lipopolysaccharide (LPS, 1 µg) into the amniotic fluid at embryonic day 16.5 as LPS group. LPS + H2 group inhaled 42% H2 gas (4 h/day) until the samples were collected. We primarily analyzed the neonatal outcomes and then compared inflammatory levels from the control group (CON), LPS group and LPS + H2 group. HE staining was performed to evaluate inflammatory levels. RNA sequencing revealed dominant differentially expressed genes. Bioinformatics analysis (GO and KEGG) of RNA-seq was applied to mine the signaling pathways involved in protective effect of H2 on the development of LPS-induced BPD. We further used qRT-PCR, Western blot and ELISA methods to verify differential expression of mRNA and proteins. Moreover, we verified the correlation between the upstream signaling pathways and the downstream targets in LPS-induced BPD model. RESULTS: Upon administration of H2, the inflammatory infiltration degree of the LPS-induced placenta was reduced, and infiltration significantly narrowed. Hydrogen normalized LPS-induced perturbed lung development and reduced the death ratio of the fetus and neonate. RNA-seq results revealed the importance of inflammatory response biological processes and Toll-like receptor signaling pathway in protective effect of hydrogen on BPD. The over-activated upstream signals [Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), Caspase1 (Casp1) and NLR family pyrin domain containing 3 (NLRP3) inflammasome] in LPS placenta were attenuated by H2 inhalation. The downstream targets, inflammatory cytokines/chemokines [interleukin (IL)-6, IL-18, IL-1ß, C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 1 (CXCL1)], were decreased both in mRNA and protein levels by H2 inhalation in LPS-induced placentas to rescue them from BPD. Correlation analysis displayed a positive association of TLR4-mediated signaling pathway both proinflammatory cytokines and chemokines in placenta. CONCLUSION: H2 inhalation ameliorates LPS-induced BPD by inhibiting excessive inflammatory cytokines and chemokines via the TLR4-NFκB-IL6/NLRP3 signaling pathway in placenta and may be a potential therapeutic strategy for BPD.

Molecular phylogenetic analysis of the East Asian hemicultrine fishes (Teleostei: Cyprinidae: Xenocypridinae), with suggestions to their generic classification and redescription of the recently described species Hemiculter yungaoi Vasil'eva et al. 2022.

The hemicultrine fishes are a group of small-sized cyprinids, widely distributed but endemic to East Asian rivers and lakes. Till now, the taxonomic boundaries and relationships within this group remain poorly explored. In the present study, we study the phylogeny of this group, providing suggestions for classification of the hemicultrine group. Using two mitochondrial and three nuclear genes, and samples representing all genera, our results showed that the group consists of seven major lineages, of which four (Hemiculterella, Hainania, Pseudolaubuca, and Anabarilius) were monophyletic and three (Hemiculter, Toxabramis, and Pseudohemiculter) were not. Based on the phylogenetic tree, we redefined the genera. We revive the genus Siniichthys, which has three species, Siniichthys bleekeri, Siniichthys lucidus, and S. varpachovskii, that were previously treated as members of the genus Hemiculter but showed distant relationships to the genus Hemiculter in our phylogenetic tree. With the new results, a diagnostic key for clades of the hemicultrine group is provided. Furthermore, we provide more detailed information on diagnostic features of the recently described species Hemiculter yungaoi (Vasil'eva et al., 2022). This work will facilitate future systematic studies, pave the way for evolutionary studies, and provide valuable information for the urgent conservation of hemicultrine fishes.

A Fast Feedforward Small-World Neural Network for Nonlinear System Modeling.

It is well-documented that cross-layer connections in feedforward small-world neural networks (FSWNNs) enhance the efficient transmission for gradients, thus improving its generalization ability with a fast learning. However, the merits of long-distance cross-layer connections are not fully utilized due to the random rewiring. In this study, aiming to further improve the learning efficiency, a fast FSWNN (FFSWNN) is proposed by taking into account the positive effects of long-distance cross-layer connections, and applied to nonlinear system modeling. First, a novel rewiring rule by giving priority to long-distance cross-layer connections is proposed to increase the gradient transmission efficiency when constructing FFSWNN. Second, an improved ridge regression method is put forward to determine the initial weights with high activation for the sigmoidal neurons in FFSWNN. Finally, to further improve the learning efficiency, an asynchronous learning algorithm is designed to train FFSWNN, with the weights connected to the output layer updated by the ridge regression method and other weights by the gradient descent method. Several experiments are conducted on four benchmark datasets from the University of California Irvine (UCI) machine learning repository and two datasets from real-life problems to evaluate the performance of FFSWNN on nonlinear system modeling. The results show that FFSWNN has significantly faster convergence speed and higher modeling accuracy than the comparative models, and the positive effects of the novel rewiring rule, the improved weight initialization, and the asynchronous learning algorithm on learning efficiency are demonstrated.

Novel trifluoromethyl ketone derivatives as oral cPLA2/COX-2 dual inhibitors for resolution of inflammation in rheumatoid arthritis.

Thirty-five trifluoromethyl hydrazones and seventeen trifluoromethyl oxime esters were designed and synthesized via molecular hybridization. All the target compounds were initially screened for in vitro anti-inflammatory activity by assessing their inhibitory effect on NO release in LPS-stimulated RAW264.7 cells, and the optimal compound was finally identified as 2-(3-Methoxyphenyl)-N'-((6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-ylidene)acetohydrazide (F26, IC50 = 4.55 ± 0.92 µM) with no cytotoxicity. Moreover, F26 potently reduced the production of PGE2 in LPS-stimulated RAW264.7 cells compared to indomethacin. The interaction of F26 with COX-2 and cPLA2 was directly verified by the CETSA technique. F26 was found to modulate the phosphorylation levels of p38 MAPK and NF-κB p65, as well as the protein expression of IκB, cPLA2, COX-2, and iNOS in LPS-stimulated rat peritoneal macrophages. Additionally, F26 was observed to prevent the nuclear translocation of NF-κB p65 in LPS-stimulated rat peritoneal macrophages by immunofluorescence localization. Therefore, the aforementioned in vitro experiments demonstrated that F26 blocked the p38 MAPK and NF-κB pathways by binding to COX-2 and cPLA2. In the adjuvant-induced arthritis model, F26 demonstrated a significant effect in preventing arthritis symptoms and inflammatory status in rats, exerting an immunomodulatory role by regulating the homeostasis between Th17 and Treg through inhibition of the p38 MAPK/cPLA2/COX-2/PGE2 and NF-κB pathways. Encouragingly, F26 caused less acute ulcerogenicity in rats at a dose of 50 mg/kg compared to indomethacin. Overall, F26 is a promising candidate worthy of further investigation for treating inflammation and associated pain with lesser gastrointestinal irritation, as well as other symptoms in which cPLA2 and COX-2 are implicated in the pathophysiology.

Influence of experiencing SARS-CoV-2 infection on anxiety levels in Chinese patients undergoing third molar surgery.

Background: In China, most of the citizens experienced SARS-CoV-2 infection since the end of 2022. The Coronavirus disease 2019 (COVID-19) pandemic affected people's physical health and also had a significant impact on mental well-being. The present study aims to discover if the experience of SARS-CoV-2 infection influences patients' anxiety toward third molar surgery in the Chinese population. Materials and methods: The present study took the form of a questionnaire survey. From January 1, 2023, to June 30, 2023, patients who went to the Stomatology Center of China-Japan Friendship Hospital (Beijing, China) for the third molar extraction were included according to the inclusion criteria. The information on COVID-19 infection and the Modified Dental Anxiety Scale (MDAS) was collected. The software SPSS 22.0 was used for the statistical analyses. Results: A total of 574 survey results were harvested in the present study. The infection rate of COVID-19 was 86.6% (p > 0.05). The Average MDAS scores between patients who had been infected with COVID-19 and patients who were never infected were not significantly different (11.65 ± 4.41 vs. 11.42 ± 4.41, p > 0.05). The subgroup analysis was conducted according to the length of time after the recovery of COVID-19 (Model 1), and the highest temperature during the infection (Model 2). In Model 1 and Model 2, the one-way ANOVA test did not find statistical significance between the groups (Model 1 p = 0.114; Model 2 p = 0.481). The MDAS scores in female patients were significantly higher than in male patients (12.29 ± 4.53 vs. 9.91 ± 3.80, p < 0.001). Patients who extracted double teeth got significantly higher MDAS scores than those who extracted single teeth before the surgery (12.03 ± 4.74 vs. 11.24 ± 4.18, p = 0.037). Conclusion: The present study did not establish a significant impact of SARS-CoV-2 infection on the anxiety levels associated with third molar surgery among Chinese patients. The potential long-term biopsychological effects of the virus warrant further investigation.

Influence of disease course and comprehensive management on blood glucose level in children and adolescents with type 2 diabetes mellitus.

AIMS/INTRODUCTION: The aim of the present study was to evaluate the status of glycemic control, and assess the effects of the disease course and comprehensive management measures on the blood glucose level in children and adolescents with type 2 diabetes mellitus. MATERIALS AND METHODS: The study collected the clinical data of type 2 diabetes patients in Beijing Children's Hospital from January 2015 to September 2020. Patients were grouped based on the disease course to compare their glycated hemoglobin (HbA1c) level, islet ß-cell function, insulin resistance and comprehensive management measures. RESULTS: Of the 170 participants, the median disease course was 2.0 years (interquartile range [IQR] 1.0-4.0 years). The baseline HbA1c was 11.2% (IQR 9.2-12.4%). According to the grouping by the disease course, the median HbA1c was the lowest (5.7% [IQR 5.3-6.1%]) in the half-year course group and the highest in the 4-year course group (9.0 [IQR 6.8%-11.3%]). Compared with the group with a disease duration <2 years, patients in the >4 years group had a lower proportion of patients with HbA1c <7% (29.2% vs 66.2%), a lower homeostasis model assessment of ß-cell function, and a lower proportion with a controlled diet, moderate-intensity exercise, regular follow up and no drug treatment. We deemed HbA1c as the dependent variable, and found that disease duration, homeostasis model assessment of ß-cell function at follow up, continuous moderate-intensity exercise, regular review and treatment regimen were significant influencing factors for glycemic control. CONCLUSIONS: Children and adolescents with type 2 diabetes and a prolonged disease course showed poor glycemic control and decreased islet ß-cell function. A good lifestyle, especially moderate-intensity exercise, can help such cases better control their blood glucose level.

[Tibiotalocalcaneal arthrodesis for end-stage ankle and hindfoot arthropathy: Short- and mid-term clinical outcomes].

OBJECTIVE: To analyze the clinical data of patients with end-stage ankle and hindfoot arthropathy who underwent tibiotalocalcaneal (TTC) arthrodesis by the same surgeon, explore the short- and mid-term clinical results, complications and functional improvement, and discuss the clinical prognosis and precautions of TTC arthrodesis. METHODS: Retrospective analysis was made on the clinical data of 40 patients who underwent TTC arthrodesis by the same surgeon from March 2011 to December 2020. In this study, 23 males and 17 females were included, with an average age of (49.1±16.0) years. All the patients underwent unilateral surgery. The clinical characteristics, imaging manifestations, main diagnosis and specific surgical techniques of the patients were recorded. The clinical outcomes were evaluated by comparison of the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) between pre-operation and at the last follow-up. The fusion healing time, symptom improvement (significant improvement, certain improvement, no improvement or deterioration) and postoperative complications were also recorded. RESULTS: The median follow-up time was 38.0 (26.3, 58.8) months. The preoperative VAS score was 6.0 (4.0, 7.0), and the AOFAS score was 33.0 (25.3, 47.3). At the last follow-up, the median VAS score was 0 (0, 3.0), and the AOFAS score was 80.0 (59.0, 84.0). All the significantly improved compared with their preoperative corresponding values (P < 0.05). There was no wound necrosis or infection in the patients. One patient suffered from subtalar joint nonunion, which was syphilitic Charcot arthropathy. The median bony healing time of other patients was 15.0 (12.0, 20.0) weeks. Among the included patients, there were 25 cases with significant improvement in symptom compared with that preoperative, 8 cases with certain improvement, 4 cases with no improvement, and 3 cases with worse symptoms than that before operation. CONCLUSION: TTC arthrodesis is a reliable method for the treatment of the end-stage ankle and hindfoot arthropathy. The function of most patients was improved postoperatively, with little impact on daily life. The causes of poor prognosis included toe stiffness, stress concentration in adjacent knee joints, nonunion and pain of unknown causes.

Analysis of dissolved oxygen influencing factors and concentration prediction using input variable selection technique: A hybrid machine learning approach.

Accurate quantification of dissolved oxygen (DO) is critically important for the protection and management of aquatic ecosystems. Successful applications have utilized mechanistic and data-driven models to simulate DO content in aquatic ecosystems. However, mechanistic models present challenges due to their complex and difficult-to-solve conditions, making them less portable. Additionally, data-driven model predictions are hindered by the challenge of numerous input variables, impacting both the running speed and prediction performance of the model. To address these challenges, water quality data and meteorological data of the Tanjiang River were obtained. The maximum information coefficient (MIC) input variable selection technique was employed to identify primary environmental factors influencing DO changes. Furthermore, coupled with support vector regression (SVR), two models (SVR and MIC-SVR) were employed to estimate the DO concentration of the Tanjiang River, and the optimal model was established. The results indicated a shift in the primary pollution factor from ammonia nitrogen to total phosphorus after recent treatment in the Tanjiang River. In comparison with the SVR model, the root mean square error (RMSE) of the MIC-SVR model was reduced by 4.46%, and the Nash-efficiency coefficient (NSE) was improved by 45.85%. In addition, study of kernel function selection revealed that considering as many kernel functions as possible is necessary for improving the performance of the SVR model. Conclusively, the proposed MIC-SVR model serves as an effective tool to analyze the relationship between DO and environmental factors, identifying the primary causes of low DO, and accurately predict the DO concentration in the Tanjiang River (especially in its middle and lower reaches), thus providing a reference for governmental decision-making on water environmental protection and water resource management.

Advanced Multifunctional Hydrogels for Enhanced Wound Healing through Ultra-Fast Selenol-SNAr Chemistry.

Fabrication of versatile hydrogels in a facile and effective manner represents a pivotal challenge in the field of biomaterials. Herein, a novel strategy is presented for preparing on-demand degradable hydrogels with multilevel responsiveness. By employing selenol-dichlorotetrazine nucleophilic aromatic substitution (SNAr) to synthesize hydrogels under mild conditions in a buffer solution, the necessity of additives or posttreatments can be obviated. The nucleophilic and redox reactions between selenol and tetrazine culminate in the formation of three degradable chemical bonds-diselenide, aryl selenide, and dearomatized selenide-in a single, expeditious step. The resultant hydrogel manifests exceptional adaptability to intricate environments in conjunction with self-healing and on-demand degradation properties. Furthermore, the resulting material demonstrated light-triggered antibacterial activity. Animal studies further underscore the potential of integrating metformin into Se-Tz hydrogels under green light irradiation, as it effectively stimulates angiogenesis and collagen deposition, thereby fostering efficient wound healing. In comparison to previously documented hydrogels, Se-Tz hydrogels exhibit controlled degradation and drug release, outstanding antibacterial activity, mechanical robustness, and bioactivity, all without the need for costly and intricate preparation procedures. These findings underscore Se-Tz hydrogels as a safe and effective therapeutic option for diabetic wound dressings.

[Relationship between short-chain fatty acids in the gingival crevicular fluid and periodontitis of stage â ¢ or â £].

OBJECTIVE: To analyze the concentration of formic acid, propionic acid and butyric acid in gingival crevicular fluid (GCF) of patients with stages Ⅲ and Ⅳ periodontitis, and their relationship with periodontitis. METHODS: The study enrolled 37 systemically healthy patients with periodontitis and 19 healthy controls who visited Department of Periodontology, Peking University School and Hospital of Stomatology from February 2008 to May 2011. Their GCFs were collected from the mesial-buccal site of one molar or incisor in each quadrant. Periodontal clinical parameters, including plaque index(PLI), probing depth(PD), bleeding index(BI), and attachment loss(AL). Concentrations of formic acid, propionic acid and butyric acid in the supernatant of the GCFs were analyzed by high-performance capillary electrophoresis (HPCE). The prediction ability of formic acid, propionic acid and butyric acid with the risk of periodontitis and the differences between grade B and grade C periodontitis were analyzed. RESULTS: In this study, 32 patients with stage Ⅲ and 5 patients with stage Ⅳ were enrolled, including 9 patients with grade B and 28 patients with grade C. Clinical periodontal variables in the patients with periodontitis were significantly higher than those in the control group (P<0.001). Formic acid was significantly lower in periodontitis than that in the control group [5.37 (3.39, 8.49) mmol/L vs. 12.29 (8.35, 16.57) mmol/L, P<0.001]. Propionic acid and butyric acid in periodontitis were significantly higher than those in the control group: Propionic acid, 10.23 (4.28, 14.90) mmol/L vs. 2.71 (0.00, 4.25) mmol/L, P < 0.001; butyric acid, 2.63 (0.47, 3.81) mmol/L vs. 0.00 (0.00, 0.24) mmol/L, P<0.001. There was no significant difference in formic acid, propionic acid and butyric acid concentrations between grade B and grade C periodontitis (P>0.05). Propionic acid and butyric acid in the deep pocket were significantly higher than in the shallow pocket, while the concentration of formic acid decreased with the increase of PD. Propionic acid (OR=1.51, 95%CI: 1.29-1.75) and butyric acid (OR=3.72, 95%CI: 1.93-7.17) were risk factors for periodontitis, while formic acid (OR=0.87, 95%CI: 0.81-0.93) might be a protective factor for periodontitis. Propionic acid (AUC=0.852, 95%CI: 0.805－0.900), butyric acid (AUC=0.889, 95%CI: 0.841－0.937), f (formic acid, AUC=0.844, 95%CI: 0.793－0.895) demonstrated a good predictive capacity for the risk of periodontitis. CONCLUSION: The concentration of formic acid decrease in the GCF of periodontitis patients, which is a protective factor for periodontitis, its reciprocal have good predictive capacity. However, propionic acid and butyric acid increase, which are risk factors for periodontitis and have good predictive capacity. The concentration of formic acid, propionic acid, and butyric acid vary with probing depth, but there is no significant difference between grade B and grade C periodontitis.

Glucose regulation of adipose tissue browning by CBP/p300- and HDAC3-mediated reversible acetylation of CREBZF.

Glucose is required for generating heat during cold-induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB-binding protein/p300 and deacetylase HDAC3 is required for glucose-induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose-specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC-1α to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.

[Essential oil of Cinnamomum camphora mitigates depression-like behavior in mice by regulating Nrf2/HO-1 pathway and inhibiting inflammatory cytokines].

This study aims to investigate the essential oil(EOL) of Cinnamomum camphora regarding its anti-depression effect and mechanism in regulating inflammatory cytokines and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. A mouse model of depression was established by intraperitoneal injection of lipopolysaccharide(LPS). Open field, elevated plus maze, and forced swimming tests were carried out to examine mouse behaviors. Western blot and qRT-PCR were employed to determine the expression of proteins and genes in the Nrf2/HO-1 pathway in the hippocampus. The levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1ß in the serum were measured by enzyme-linked immunosorbent assay(ELISA). The changes of apoptosis in mouse brain were detected by Tunel staining. Compared with the blank control group, the model group showed shortened distance travelled and time spent in the central zone and reduced number of entries in the central zone in the open field test. In the elevated plus maze test, the model group showed reduced open arm time(OT%) and open arm entries(OE%). In the force swimming test, the model group showed extended duration of immobility compared with the blank control group. Compared with the model group, the treatment with EOL significantly increased the distance travelled and time spent in the central zone and increased the number of entries in the central zone in the open field test. In addition, EOL significantly increased the OT% and OE% in the elevated plus maze and shor-tened the immobility duration in the forced swimming test. The model group showed lower expression levels of Nrf2 and HO-1 and hig-her levels of TNF-α, IL-6, and IL-1ß than the blank control group. Compared with the model group, the treatment with EOL up-regulated the expression levels of Nrf2 and HO-1 and lowered the levels of TNF-α, IL-6, and IL-1ß. The Tunel staining results showed that the apoptosis rate in the brain tissue of mice decreased significantly after the treatment with EOL. To sum up, EOL can mitigate the depression-like behaviors of mice by up-regulating the expression of Nrf2 and HO-1 and preventing hippocampal inflammatory damage. The findings provide empirical support for the application of EOL and aromatherapy in the treatment of depression.

Nicotinamide promotes the differentiation of functional corneal endothelial cells from human embryonic stem cells.

Corneal transplantation represents the primary therapeutic approach for managing corneal endothelial dysfunction, but corneal donors remain scarce. Anterior chamber cell injection emerges as a highly promising alternative strategy for corneal transplantation, with pluripotent stem cells (PSC) demonstrating considerable potential as an optimal cell source. Nevertheless, only a few studies have explored the differentiation of functional corneal endothelial-like cells originating from PSC. In this investigation, a chemical-defined protocol was successfully developed for the differentiation of functional corneal endothelial-like cells derived from human embryonic stem cells (hESC). The application of nicotinamide (NAM) exhibited a remarkable capability in suppressing the fibrotic phenotype, leading to the generation of more homogeneous and well-distinctive differentiated cells. Furthermore, NAM effectively suppressed the expression of genes implicated in endothelial cell migration and extracellular matrix synthesis. Notably, NAM also facilitated the upregulation of surface marker genes specific to functional corneal endothelial cells (CEC), including CD26 (-) CD44 (-∼+-) CD105 (-) CD133 (-) CD166 (+) CD200 (-). Moreover, in vitro functional assays were performed, revealing intact barrier properties and Na+/K+-ATP pump functionality in the differentiated cells treated with NAM. Consequently, our findings provide robust evidence supporting the capacity of NAM to enhance the differentiation of functional CEC originating from hESC, offering potential seed cells for therapeutic interventions of corneal endothelial dysfunction.

Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy.

The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy.