Ghrelin regulates the proliferation and apoptosis of high glucose-induced islet cells through the PI3K-Akt signaling pathway.

Ghrelin may have therapeutic value in mitigating insulin resistance and type 2 diabetes, based on which we further explore the action mechanism of ghrelin on islet cells in this research. In the course of experiments, MIN6 cells were induced by glucose and then treated with acylated or unacylated ghrelin. The effects of ghrelin on the viability, proliferation, apoptosis, and insulin release of high glucose-induced islet cells were detected by Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, and enzyme-linked immunosorbent assays, respectively. Meanwhile, cells were treated with LY294002 to explore whether and how the inhibited phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway participated in the internal mechanism of ghrelin-regulating islet cells. Western blotting was performed to quantify the expression levels of Bcl-2, Bax, Cleaved caspase-3, PI3K, and AKT. As a result, ghrelin alleviated high glucose-induced suppression of viability and proliferation and promotion on apoptosis of MIN6 cells. Ghrelin also attenuated the inhibitory effects of high glucose on expression levels of PI3K-Akt signaling axis-related proteins and insulin release in MIN6 cells. Besides, ghrelin weakened the impacts of high glucose on boosting MIN6 cell apoptosis and hindering proliferation through the PI3K-Akt signaling axis. Collectively, ghrelin regulates the proliferation and apoptosis of high glucose-induced islet cells through the PI3K-Akt signaling pathway.

A cross-sectional evaluation of knowledge among Chinese dentists regarding the treatment of traumatic injuries in primary teeth.

BACKGROUND/AIM: Injuries to the primary dentition affect children's esthetics, function, and mental health. They may also affect the development of the permanent teeth. The knowledge of dentists about deciduous tooth trauma is rarely evaluated. The aim of this study was to evaluate the knowledge and attitude of dentists in China regarding traumatic dental injuries to primary teeth. MATERIAL AND METHODS: A self-administered online questionnaire containing questions on demographic data and knowledge based on a clinical scenario was given to a purposive sample of dentists, recruited by a non-probability convenience sampling method. The chi-square test was used for statistical analysis, with the significance level set at P <.05. RESULTS: A total of 394 out of 409 dentists provided valid data. There was no significant difference in demographic data. Questions about the treatment of hard dental tissue injuries in primary teeth presented a correct-response rate of 66.4%, with the highest correct-response rate for enamel fracture (n = 368, 93.4%) and lowest for complicated crown-root fracture with pulp exposure (n = 104, 26.4%). Questions about treatment of luxation injuries in primary teeth presented a correct-response rate of 66.6%, with subluxation presenting the highest correct-response rate (n = 391, 99.2%). Factors associated with higher correct-response rates were specialist disciplines, educational qualifications, workplaces, experience of injured teeth treated, and educational experience about primary tooth trauma. No significant differences were found in the correct-response rates of dentists with different years of work experience. Lack of cooperation from children was considered a major obstacle for treatment. Special lectures and Internet courses were the most preferred methods of obtaining knowledge. CONCLUSION: The results suggest that it is necessary to enhance dental trauma education for dentists in China. More attention needs to be paid to trauma in primary dentition to ensure adequate treatment for traumatized primary teeth.

Trends, Characteristics, and Success Rates of Treatment for Severe Early Childhood Caries Under General Anesthesia: A Retrospective Study in Northwest China.

BACKGROUND/OBJECTIVE: To retrospectively analyze the characteristics, tendencies, and success rates of dental treatments for severe early childhood caries (SECC) under general anesthesia (GA) in in northwest China. STUDY DESIGN: Children diagnosed with SECC were included in this retrospective study. From January 2015 to December 2018, they received dental treatment under GA at Affiliated Stomatology Hospital of Xi'an Jiaotong University. Demographic information, caries status and treatment characteristics were collected from electronic medical record system. Success rates of different treatments at 6-month and 12-month follow up were also analyzed. RESULTS: A total of 846 children (477 male, 369 female) received dental treatment under GA. The case number was increased from 148 in 2015 to 278 in 2018. There were 81.2% and 70.8% of the children participated the 6-month and 12-month follow up. SSC and pulpotomy was the most successful restorations and pulp therapy, with the success rate of 97.09% and 93.98% in 12-month follow up, respectively. The use of crown restorations (including composite resin crown and stainless steel crown) and pulp reservation therapies (including indirect pulp therapy and pulpotomy) were significantly increased while composite resin filling and pulpectomy decreased during 2015 to 2018. CONCLUSION: There has been an increasing demand for dental treatment under GA for children with SECC in northwest China, with a trend toward younger ages. With better clinical outcomes, crown restorations and pulp reservation therapies were the fastest-growing treatments under GA.

Step-by-step teaching method: improving learning outcomes of undergraduate dental students in layering techniques for direct composite resin restorations.

BACKGROUND: Layering techniques for direct composite resin restorations might be complicated for inexperienced learners, as a number of materials and instruments are required at each step. The present study aimed to compare and assess the teaching effect of step-by-step and all-in-one teaching methods in layering techniques for direct composite resin restorations among undergraduate dental students. METHODS: A total of 68 junior dental students participated in this study, which was a prospective and single-blind trial. The students were randomly divided into a step-by-step group (experimental group, n = 34) and all-in-one group (control group, n = 34). The same teacher taught the two groups, ensuring a comparable teaching effect. The final score of each student was an average of scores by two experts who were blinded to the grouping. The scoring system was consisted by five parts. Each part was assigned scores of 3.0, 1.5, or 0. The total maximum score was 15 and minimum was 0. The total time taken by each group was also calculated. RESULTS: The values of the quality of tooth restorations evaluated by experts for step-by-step and all-in-one groups were 11.29 ± 2.13 from 15 and 9.00 ± 2.71 from 15 (t = 3.88, P < 0.001), respectively. In addition, the time spent by the experimental group was significantly lesser than that spent by the control group, which was 122.47 ± 2.82 and 137.18 ± 6.75 min, respectively (t = 11.72, p < 0.001). CONCLUSION: With regard to the layering techniques for direct composite resin restorations, the outcomes were better in the step-by-step group than in the all-in-one group.

Worldwide tendency and perspectives in traumatic dental injuries: A bibliometric analysis over two decades (1999-2018).

BACKGROUND/AIMS: Traumatic dental injuries (TDIs) are considered to be a public dental health problem worldwide. The aim of the current study was to provide the worldwide tendency and perspectives in TDIs in the last two decades via bibliometric analysis. METHODS: ''Tooth injuries'' was searched as the Medical Subject Headings term within PubMed with the date range from 1999 to 2018. Two investigators perused information in the articles according to the inclusion and exclusion criteria. The articles were independently categorized according to the following aspects: (a) annual scholarly output; (b) leading countries or regions; (c) leading journals; (d) productive authors; (e) citations; (f) study design; (f) distribution of topics; and (g) the type of dentition and TDIs. VOSviewer 1.6.7 and Citespace 5.2 were used for analyzing and visualizing bibliometric networks. RESULTS: A total of 2627 articles about traumatic dental injuries were published and indexed in PubMed during the two decades, and the number of publications on traumatic dental injuries was rising in general. The research outputs were mainly concentrated in developed countries and affiliated hospitals of universities. Brazil was the most productive country. The journal Dental Traumatology had the most contributions to the scientific research of traumatic dental injuries. "Case report" was the most frequent type of article (36.50%), followed by cross-sectional studies (19.57%) and case-control studies (13.67%). Most studies focused on the treatment of TDIs (38.94%), especially for avulsion (21.01%), crown fracture (9.71%), and intrusion (5.25%). Permanent teeth (66%) were the dominant dentition. CONCLUSION: There is a lack of high-quality well-designed studies such as cohort studies. The number of publications on prevention and the primary dentition is disproportionate in relation to their significance.

Bactericidal effect of a diode laser on Enterococcus faecalis in human primary teeth-an in vitro study.

BACKGROUND: In recent years, the diode laser (810 nm) has been used for root canal disinfection, which plays an important role in endodontic therapy. This study was undertaken to evaluate the disinfecting ability of a diode laser in experimentally infected root canals of primary teeth. METHODS: Human retained mandibular primary anterior teeth without apical foramen resorption were selected and contaminated with Enterococcus faecalis for 21 days. The specimens were randomly divided into four groups: the negative group (no treatment), positive group (5.25% NaOCl), diode laser group (diode laser), and diode-NaOCl group (diode laser combined with NaOCl). The disinfecting abilities of the treatments were measured by the numbers of bacteria, scanning electron microscopy and confocal laser microscopy (live-dead staining). RESULTS: Eighty teeth were selected. After irradiation and irrigation, the elimination of bacteria and the smear layer in the laser groups and positive group were significantly superior, compared with the negative group (p < 0.01). In the diode-NaOCl group, bacterial reduction reached nearly 100% on the surfaces of root canals; live bacteria were rarely observed, even in deeper dentinal tubules. CONCLUSION: Use of a diode laser, especially in combination with NaOCl, was effective for disinfecting infected root canals of primary teeth.

Comparison of Endoflas and Zinc Oxide Eugenol as Root Canal Filling Materials for Pulpectomy in Deciduous Teeth: a Systematic Review and Meta-Analysis.

Objectives: To evaluate and compare the effectiveness of Endoflas and Zinc Oxide Eugenol (ZOE) as root canal filling materials (RCFMs) for the pulpectomy of deciduous teeth by analyzing multiple clinical and radiographic success and failure follow-ups in previously published studies. Data: All clinical studies that investigated the pulpectomy of the deciduous teeth of children aged 3-9 years. Sources: The databases used for source identification included MEDLINE (via PubMed), Scopus, Web of Science, and the Cochrane Library. No limitations were imposed on the publication year or language. The selection of studies and extraction of relevant study characteristics were conducted from December 26, 2021, to September 7, 2023. Additionally, the risk of bias (RoB) in the included studies was evaluated by using a RoB instrument (RoB 2). Eligible studies were then combined, and a random-effects model was applied by using the maximum likelihood estimations of log risk ratios and their corresponding 95% confidence intervals. Study selection: Of the 3913 records found in the abovementioned databases, nine were eligible for systematic review and eight were eligible for meta-analysis. The studies included 628 pulpectomies of deciduous molar teeth in children. The overall results showed that compared with Endoflas, ZOE was associated with a higher risk ratio for clinical evaluation (LOG[RR] = 0.06, CI 0.03-0.09, p-value 0.001) and radiographic evaluation (LOG[RR] = 0.68, CI 0.35-1.00, p-value 0.001). This association was highly significant at 6- and 9-month follow-ups. Conclusion: Compared with ZOE, Endoflas was associated with a lower risk of the clinical and radiographic failure of deciduous teeth pulpectomy and a 6%-6.8% higher risk ratio, especially at 6- and 9-month follow-ups. Clinical significance: This study suggests the superiority of Endoflas over ZOE as an RCFM for deciduous teeth.

Free radical mechanisms of ammonium sulfate as intensively used industrial materials on suppressing organic pollutants.

Organic free radicals are critical intermediates for the generation and inhibition of organic pollutants during industrial processes. Clarifying the free radical mechanism of pollutant inhibition is significant for their efficient control. Ammonium sulfate is intensively used in industrial materials to suppress organic pollutants. In this study, organic free radical intermediate species in metal-catalyzed reactions inhibited by ammonium sulfate were identified using continuous-wave electron paramagnetic resonance (EPR) spectroscopy, providing direct evidence for the free radical mechanisms of organic pollutants inhibition. The transverse (T2) and longitudinal (T1) relaxation time variations catalyzed by different metal catalysts in the presence of ammonium sulfate were compared using pulsed-wave EPR. Consequently, after the addition of ammonium sulfate, the observed increase in T2 suggests that ammonium sulfate leads to radical concentration reduction. A decrease in the T1 relaxation time suggests the enhanced interaction between organic radicals and metals, which is an obstacle to subsequent radical reactions. Therefore, ammonium sulfate dominantly changed the free radical intermediates species, concentrations, and their reactivity, and then inhibited the organic pollutants formations. The inhibition mechanisms of ammonium sulfate on metal-catalyzed pollutants were then proposed combining EPR analysis, X-ray characterization, and high-resolution mass spectrometry screening. As a result, (1) occupying the active sites of metal catalysis and (2) inhibiting free radical intermediates are the two main intrinsic inhibition mechanisms of ammonium sulfate. The findings provide new perspectives on the efficient inhibition of organic pollutants in industrial processes involving various metal catalysts.

Survival Analysis and Risk Factors of Pulpectomy among Children with Severe Early Childhood Caries Treated under General Anesthesia: A Retrospective Study.

OBJECTIVES: This study aims to retrospectively evaluate the survival rate of pulpectomy performed under dental general anesthesia (DGA) through long-term follow-up and to explore the risk factors associated with treatment failure. METHODS: The medical records of the children who were diagnosed with S-ECC and received pulpectomy treatment under general anesthesia (GA) from 1 August 2014 to 1 December 2019, in the Stomatological Hospital of Xi'an Jiaotong University, were collected. Two dentistry postgraduates extracted the necessary information and filled in a predesigned excel form. Survival analysis was performed using the Kaplan-Meier method. The shared frailty model was used to explore possible factors affecting the success rate of pulpectomy in primary teeth. RESULTS: A total of 381 children (mean age 3.49 ± 0.90) with S-ECC and 1220 teeth were included in the study, including 590 primary anterior teeth and 630 primary molars. The overall 35-month survival rate was 38.5%, which was 52.9% for anterior teeth and 31.1% for molars. The overall median survival time was 31 months, in which anterior teeth were 35 months and molars were 26 months. The older the children were, the greater the risk of treatment failure (HR 1.56, 95% CI 1.09, 2.24). The risk of pulpectomy failure of primary molars was 1.9 times that of primary anterior teeth (95% CI 1.36, 2.65) and the teeth with abnormal radiological findings before treatment was 1.41 times higher than that of teeth without imaging abnormalities (95% CI 1.74, 3.36). CONCLUSION: The survival rate of primary tooth pulpectomy is acceptable but decreased gradually with time. The failure rate of pulpectomy in primary molars is higher than that of primary anterior teeth. When the primary caries has extended to the pulp and resulted in a nonvital lesion, pulpectomy could be an option for maximum retention of the primary tooth.

Incidence and risk factors of unplanned retreatment following dental general anesthesia in children with severe early childhood caries.

Objective: This study aimed to retrospectively describe the unplanned retreatment of dental general anesthesia (DGA) in children with severe early childhood caries (S-ECC) and explore potential factors that may influence the outcome of DGA treatment. Methods: Medical records of children with S-ECC who received DGA treatment were screened, and necessary data were extracted. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the DGA survival rate and explore the potential factors affecting the success rate of DGA treatment. Results: Medical records of 852 children were included; 509 (59.7%) children with 1,212 (10.7%) teeth underwent unplanned retreatment. Restoration failure (30.12%) and new caries (29.46%) accounted for the most significant proportion of all failures. The median survival times were 510 and 1,911 days at the child and tooth levels, respectively. Unplanned retreatment risk was associated with the age of S-ECC children, frequency of follow-up, and fluoride application (hazard ratio = 0.97, 0.78, 0.69, P < 0.001). Conclusion: The treatment outcome of DGA administered to children with S-ECC was satisfactory at the tooth level from the perspective of the incidence of unplanned retreatment. Restoration failure was the main reason for the high unplanned retreatment rate. Strategies for a better outcome of DGA include improving the professional knowledge and skills of pediatric dentists and enhancing compliance of parents/patients. Health education and regular topical fluoride application may improve the success rate of DGA treatment.

The IGF2BP3-COPS7B Axis Facilitates mRNA Translation to Drive Colorectal Cancer Progression.

Many studies have provided valuable information about genomic and transcriptomic changes that occur in colorectal cancer. However, protein abundance cannot be reliably predicted by DNA alteration or mRNA expression, which can be partially attributed to posttranscriptional and/or translational regulation of gene expression. In this study, we identified increased translational efficiency (TE) as a hallmark of colorectal cancer by evaluating the transcriptomic and proteomic features of patients with colorectal cancer, along with comparative transcriptomic and ribosome-protected mRNA analysis in colon epithelial cells and colon cancer cells. COP9 signalosome subunit 7B (COPS7B) was among the key genes that consistently showed both significant TE increase and protein elevation without transcriptional alteration in colorectal cancer. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) enhanced the TE of COPS7B mRNA to promote colorectal cancer growth and metastasis. COPS7B was found to be a component of the ribo-interactome that interacted with ribosomes to facilitate ribosome biogenesis and mRNA translation initiation. Collectively, this study revealed the proteomic features of colorectal cancer and highlighted elevated mRNA translation as a hallmark of colorectal cancer. The identification of the IGF2BP3-COPS7B axis underlying the increased protein synthesis rate in colorectal cancer provided a promising therapeutic target to treat this aggressive disease. SIGNIFICANCE: Increased expression of COPS7B mediated by IGF2BP3 elevates the translational efficiency of genes enriched in mRNA translation and ribosome biogenesis pathways, promoting protein synthesis and driving progression in colorectal cancer.

The role of alternative splicing in lung cancer.

Aberrant alternative splicing (AS) events are frequently observed in lung cancer, which can be attributed to aberrant gene AS, alterations in splicing regulatory factors, or changes in splicing regulatory mechanisms. Consequently, the dysregulation of alternative RNA splicing is the fundamental cause of lung cancer. In this review, we have summarized the pivotal role of AS in the development, progression, invasion, metastasis, angiogenesis, and drug resistance of lung cancer. Ultimately, this review emphasizes the potential of AS as biomarkers in lung cancer prognosis and diagnosis, and introduces some applications of AS isoform in the treatment of lung cancer. The comprehension of the AS may provide a glimmer of hope for the eradication of lung cancer.

Compromised browning in white adipose tissue of ageing people.

BACKGROUND: Adipose tissue plays a pivotal role in the pathology of metabolic disorders. In the past decade, brown and brown-like adipose tissues were detected in adult humans and show therapeutic potential in ageing-related metabolic diseases. OBJECTIVE: This study investigated expressions of major brown adipose markers in white adipose tissue (WAT) of different ages. Their associations with metabolic parameters and key adipokines were interrogated. DESIGN: Cross-sectional study, 2019-2021. METHODS: We recruited 21 young, 67 middle-aged, and 34 older patients. Omental adipose tissues were collected, and expressions of key brown markers and adipokines and the adipocyte size were evaluated. The fat depot distribution was evaluated by computed tomography. RESULTS: UCP1 and PRDM16 mRNA expressions declined with ageing in WAT and were more associated with age, than with the body mass index (BMI). The increased visceral adipose tissue (VAT) amount, as well as the VAT to subcutaneous adipose tissue (SAT) ratio, was decreased in the highest tertile of UCP1 expression, while individuals in different PRDM16 mRNA tertiles exhibited similar fat distribution. UCP1 mRNA was positively correlated with ADIPOQ and the strength of the correlation declined with ageing. In contrast, the association between UCP1 and LEP was insignificant in young and middle-aged groups but became significantly correlated in the older-people group. We also found a positive correlation between UCP1 and PRDM16. CONCLUSIONS: PRDM16 and UCP1, despite their key functions in adipose browning, exhibit differential clinical correlations with metabolic features in human WAT in an age-dependent manner. These two genes may participate in the pathogenesis of ageing-related metabolic diseases, but with distinct mechanisms.

Differential correlation between time in range and eGFR or albuminuria in type 2 diabetes.

INTRODUCTION: As a CGM-derived indicator, 'time in range' (TIR) is emerging as a key indicator for accurate assessment of glycaemic control. However, there is few report focusing on the correlation of TIR with albumuria and renal fuction. The aim of this work was to investigate whether TIR, as well as nocturnal TIR and hypoglycaemic events is related to the presence and severity of albuminuria and decrease of eGFR in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 823 patients were enrolled in this study. All patients received continuous glucose monitoring, TIR indicating the percentage of time that blood glucose was in the range of 3.9-10.0 mmol/L. The Spearman analysis was applied to analyze the relationship between TIR (or nocturnal TIR) and ACR. Logistic regression was used to explore whether TIR (or nocturnal TIR) is an independent risk factor for albuminuria. RESULTS: The prevalence of albuminuria decreased with increasing TIR quartiles. Binary logistic regression revealed that TIR as well as nocturnal TIR was obviously related to the presence of albuminuria. Multiple regression analysis found that only nocturnal TIR was obviously related to the severity of albuminuria. In our study, eGFR was significantly associated with the number of hypoglycemic events. CONCLUSIONS: In T2DM patients, TIR and nocturnal TIR is associated with the presence of albuminuria independent of HbA1c and GV metrics. Nocturnal TIR shows better correlation than TIR. The role of TIR especially nocturnal TIR in the evaluation of diabetes kidney disease should be emphasized.

A facile and total water-soluble fluorescent organic nanoparticles-based sensor for Hg2+ detection and its application in tea samples.

In this study, a novel FONs-based sensor P-M(w) was synthesized using 1-Pyrenecarboxaldehyde and L-methionine through facile hydrothermal strategy. The fluorescence emission peaks of the acquired P-M(w) would show specific changes after the addition of Hg2+ due to interfering the PET process and inducing nano-structure conformational rigidification of P-M(w). Notably, the water-soluble FONs-based sensor was firstly used to detect Hg2+ in tea samples providing a new material choice for the fluorescence sensor construction of metal ion detection. Besides, the qualitative and quantitative analysis of Hg2+ could be carried out with P-M (w) at a very low concentration (1 µg/mL) meaning that the acquired P-M(w) synthesized by few grams of reactants may satisfy the detection of approximate fifty thousand samples.

Relationship Between Acyl and Desacyl Ghrelin Levels with Insulin Resistance and Body Fat Mass in Type 2 Diabetes Mellitus.

Purpose: Although strong evidence suggests that ghrelin plays an important role in regulating energy balance, the effects of acylated ghrelin (AG) and deacylated ghrelin (DAG) on fat mass are largely undefined. This study aimed to investigate the differential associations of both forms of ghrelin with insulin resistance and body fat mass in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A total of 162 patients with type 2 diabetes were recruited and classified based on BMI and visceral fat area (VFA) as VFA normal group (n = 78), normal-BMI VFA obesity group (n = 20) and high-BMI VFA obesity group (n = 64). VFA and subcutaneous fat area (SFA) were detected by bioelectrical impedance analysis. Blood samples were collected to measure fasting glucose, insulin, lipids, AG and DAG levels after clinical examination. Results: Compared with VFA normal group, DAG levels were significantly lower (421.7 ± 106.0 and 388.7 ± 96.5 pg/mL vs 524.4 ± 141.5 pg/mL, P < 0.01) in the two VFA obesity groups. No significant difference was found in AG levels within three groups. Among all subjects, BMI, VFA, SFA, fasting insulin and HOMA-IR were negatively correlated with DAG but positively with AG/DAG ratio (P < 0.01). In contrast, AG was positively correlated with HOMA-IR and fasting glucose (P < 0.01). Multiple stepwise regression analysis showed that fasting glucose was the independent factor of AG, VFA and HOMA-IR were the independent factors related to DAG. Conclusion: DAG levels have a strong negative association with excess body fat mass and insulin resistance, whereas AG levels are closely related to elevated blood glucose levels in T2DM patients.

Spectroscopy, Structure, Biomacromolecular Interactions, and Antiproliferation Activity of a Fe(II) Complex With DPA-Bpy as Pentadentate Ligand.

An Fe(II) complex with DPA-Bpy (DPA-Bpy = N,N-bis(2-pyridinylmethyl)-2,20-bipyridine-6 -methanamine) as the ligand was synthesized and characterized to mimic bleomycin. The binding constants (K b) of the complex with calf thymus DNA and human serum albumin (HSA) were quantitatively evaluated using fluorescence spectroscopy, with K b as 5.53×105 and 2.40×104 M-1, respectively; the number of the average binding site (n) is close to 1. The thermodynamic analyses suggested that the electrostatic interactions exist between the complex and DNA, and the hydrogen bonding and Van der Waals force exist for the complex and HSA. The Fe complex exhibits cleavage ability toward pBR322 DNA, and the crystal structure of the HSA Fe complex adduct at 2.4 Å resolution clearly shows that His288 serves as the axial ligand of the Fe center complexed with a pentadentate DPA-Bpy ligand. Furthermore, the cytotoxicity of the complex was evaluated against HeLa cells. Both the Fe complex and HSA Fe complex adduct show obvious effect on cell proliferation with an IC50 of 1.18 and 0.82 µM, respectively; they induced cell apoptosis and arrested cell cycles at S phase. This study provides insight into the plausible mechanism underlying their metabolism and pharmacological activity.

Time in range, as an emerging metric of glycemic control, is associated with orthostatic blood pressure changes in type 2 diabetes.

AIMS: To exlpore whether time in range(TIR) was associated with orthostatic blood pressure(BP) changes in type 2 diabetes(T2DM). METHODS: A total of 342 T2DM patients were recruited. TIR was defined as the time percentage spent within the target range(3.9-10.0 mmol/L). Orthostatic hypotension(OH) and orthostatic hypertension(OHT) were defined as a decrease or an increase of at least 20 mmHg in SBP and/or 10 mmHg in DBP after standing for 3 min. RESULTS: Compared with orthostatic normotension group, patients with OH or OHT showed lower levels of TIR (P < 0.001). The prevalences of OH and OHT both decreased with ascending TIR tertiles (OH, P < 0.001; OHT, P = 0.019), and both absolute SBP and DBP changes were negatively correlated with TIR (r = -0.171, -0.190, P < 0.05). After stratifying by BMI, only the prevalence of OH in the lower layer and the prevalence of OHT in the higher layer remained significant difference among tertiles of TIR. Multivariate logistics regression revealed that lower TIR and lower BMI were risk factors for OH, whereas lower TIR but higher BMI were risk factors for OHT. CONCLUSIONS: We find a differential correlation dependent of BMI milieus between TIR and orthostatic BP status.

Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2.

Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A (Ldha), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1ß (IL-1ß). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1ß was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism.

The RNA-Binding Motif Protein Family in Cancer: Friend or Foe?

The RNA-binding motif (RBM) proteins are a class of RNA-binding proteins named, containing RNA-recognition motifs (RRMs), RNA-binding domains, and ribonucleoprotein motifs. RBM proteins are involved in RNA metabolism, including splicing, transport, translation, and stability. Many studies have found that aberrant expression and dysregulated function of RBM proteins family members are closely related to the occurrence and development of cancers. This review summarizes the role of RBM proteins family genes in cancers, including their roles in cancer occurrence and cell proliferation, migration, and apoptosis. It is essential to understand the mechanisms of these proteins in tumorigenesis and development, and to identify new therapeutic targets and prognostic markers.