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Hard palate consists anteriorly of the palatal process of the maxilla (ppmx) and posteriorly of the palatal process of the palatine (ppp). Currently, palatal osteogenesis is receiving increasing attention. This is the first study to provide an overview of the osteogenesis process of the mouse hard palate. We found that the period in which avascular mesenchymal condensation becomes a vascularized bone structure corresponds to embryonic day (E) 14.5 to E16.5 in the hard palate. The ppmx and ppp differ remarkably in morphology and molecular respects during osteogenesis. Osteoclasts in the ppmx and ppp are heterogeneous. There was a multinucleated giant osteoclast on the bone surface at the lateral-nasal side of the ppmx, while osteoclasts in the ppp were more abundant and adjacent to blood vessels but were smaller and had fewer nuclei. In addition, bone remodeling in the hard palate was asymmetric and exclusively occurred on the nasal side of the hard palate at E18.5. During angiogenesis, CD31-positive endothelial cells were initially localized in the surrounding of palatal mesenchymal condensation and then invaded the condensation in a sprouting fashion. At the transcriptome level, we found 78 differentially expressed genes related to osteogenesis and angiogenesis between the ppmx and ppp. Fifty-five related genes were up/downregulated from E14.5 to E16.5. Here, we described the morphogenesis and the heterogeneity in the osteogenic and angiogenic genes profiles of the ppmx and ppp, which are significant for subsequent studies of normal and abnormal subjects.

This study assessed the effect and potential molecular mechanism of tanshinone IIA on fracture healing. Mice model with fracture were established. Digital radiographic photographic system was used to detect callus formation after treatment with tanshinone II A (Tan IIA) and alkaline phosphatase (ALP) staining analyzed ALP activity. Osteoblast proliferation was also measured. Western blot and Quantitative real-time PCR (qRT-PCR) measured osteogenic markers expression. Compared with control group, Tan IIA treatment could increase callus formation, stimulate osteoblast proliferation, osteogenic proteins and genes expression, and activate mTORC1 signaling pathway. However, Tan IIA’s effects were significantly inhibited after rapamycin treatment. Tan IIA regulates osteoblast differentiation by mTORC1 signaling and promotes intramembranous ossification in the process of callus formation, which accelerates bone healing.

Sepsis and sepsis‐induced skeletal muscle atrophy are common in patients in intensive care units with high mortality, while the mechanisms are controversial and complicated. In the present study, the atrophy of skeletal muscle was evaluated in sepsis mouse model as well as the apoptosis of muscle fibres. Sepsis induced atrophy of skeletal muscle and apoptosis of myofibres in vivo and in vitro. In cell‐based in vitro experiments, lipopolysaccharide (LPS) stimulation also inhibited the proliferation of myoblasts. At the molecular level, the expression of polo‐like kinase 1 (PLK1) and phosphorylated protein kinase B (p‐AKT) was decreased. Overexpression of PLK1 partly rescued LPS‐induced apoptosis, proliferation suppression and atrophy in C2C12 cells. Furthermore, inhibiting the AKT pathway deteriorated LPS‐induced atrophy in PLK1‐overexpressing C2C12 myotubes. PLK1 was found to participate in regulating apoptosis and E3 ubiquitin ligase activity in C2C12 cells. Taken together, these results indicate that sepsis induces skeletal muscle atrophy by promoting apoptosis of muscle fibres and inhibiting proliferation of myoblasts via regulation of the PLK1‐AKT pathway. These findings enhance understanding of the mechanism of sepsis‐induced skeletal muscle atrophy.

Objective The aim of this study was to confirm the pathogenic variants, explore the genotype–phenotype correlation and characteristics of Chinese patients with Treacher Collins syndrome (TCS). Design Clinical details of 3 TCS family cases and 2 sporadic cases were collected and analyzed. Whole-exome sequencing and Sanger sequencing were conducted to detect causative variants. Setting Tertiary clinical care. Patients This study included 8 patients clinically diagnosed with TCS who were from 3 familial cases and 2 sporadic cases. Main Outcome Measures When filtering the database, variants were saved as rare variants if their frequency were less than 0.005 in the 1000 Genomes Project Database, the Exome Aggregation Consortium (ExAC) browser, and the Novogene database, or they would be removed as common ones. The pathogenic variants identified were verified by polymerase chain reaction. The sequencing results were analyzed by Chromas 2.1 software. Results Two novel pathogenic variants (NM_000356.3: c.537del and NM_000356.3: c.1965_1966dupGG) and 2 known pathogenic variants (NM_000356.3: c.1535del, NM_000356.3: c.4131_4135del) were identified within TCOF1 which are predicted to lead to premature termination codons resulting in a truncated protein. There was a known missense SNP (NM_015972.3: c.139G>A) within POLR1D. No phenotype–genotype correlation was observed. Instead, these 8 patients demonstrated the high genotypic and phenotypic heterogeneity of TCS. Conclusions This study expands on the pathogenic gene pool of Chinese patients with TCS. Besides the great variation among patients which is similar to international reports, Chinese patients have their own characteristics in clinical phenotype and pathogenesis mutations.

Background Chemical exchange saturation transfer (CEST) is an emerging metabolic MRI technique to map creatine distribution in the myocardium. Purpose To investigate the feasibility of using a contrast-free CEST technique to evaluate cardiac involvement in amyloid light-chain (AL) amyloidosis. Study type Prospective. Population Forty patients with biopsy-proven AL amyloidosis (age 57.6 ± 9.1 years, 31 males) and 20 healthy controls (age 42.8 ± 13.8 years, 13 males). Field strength/sequence A 3.0 T, CEST imaging using a single-shot FLASH sequence, T1 mapping with a modified Look-Locker inversion recovery sequence and late gadolinium enhancement (LGE) imaging with a phase-sensitive inversion recovery gradient echo sequence. Assessment The average CEST was calculated in the basal short-axis slice of the entire left ventricle and septum. LGE was assessed subjectively (none/patchy/global) and extracellular volume (ECV), CEST and T1 maps generated. Statistical tests Comparison between patient groups and healthy controls was performed by one-way analysis of variance with post hoc Bonferroni correction. Correlation was assessed using the Pearson's r correlation or Spearman ρ correlation. Statistical significance was defined as P Results Global (0.09 ± 0.03 vs. 0.11 ± 0.02) and septal (0.09 ± 0.03 vs. 0.11 ± 0.03) basal short-axis CEST was significantly decreased in patients with AL amyloidosis compared to the controls. Global CEST correlated significantly with Mayo stage (ρ = -0.508), NYHA Class (ρ = -0.430), LVEF (r = 0.511), mass index (r = -0.373), LGE (ρ = -0.537), ECV (r = -0.544), and T2 (r = -0.396). Septal CEST correlated significantly with LVEF (r = 0.395), LGE (ρ = -0.330), and ECV (r = -0.391). Data conclusions This study highlights the potential of CEST MRI to identify cardiac involvement and evaluate disease burden and to give insight into cellular changes intermediary between function and structure in AL amyloidosis patients. Evidence level 2 TECHNICAL EFFICACY: Stage 2.

To study the residual performance of the welded hollow spherical joint after exposure to high temperatures. A total of 12 welded hollow spherical joint specimens are heated to six different preselected temperatures and subsequently air-cooled and water-cooled to the ambient temperature. Axial compressive tests are thereafter performed until the joints are damaged. The displacement characteristics, strain development, failure modes, stiffness, ductility, and load bearing capacity of specimens are investigated. The results show that the mechanical properties of spherical joints are considerably affected by the temperatures and cooling methods. Under the air-cooling condition, both the stiffness and compressive load of spherical joints decrease with an increase in the exposed temperature, and the ductility increases considerably. Under the water-cooling condition, the stiffness and ductility of spherical joints decrease with the increase in exposed temperature. The yield and ultimate loads decrease when the temperature is up to 500 °C and then gradually increase when the temperature exceeds 500 °C.

Background: The incidence of oral squamous cell carcinoma (OSCC) is increasing, with an estimated 369,000 new patients each year worldwide. Surgery is the primary treatment modality for early-stage OSCC, but there is scant evidence to prove the value of elective neck dissection (END) for relatively small early-stage OSCC. This study aimed to identify factors predicting survival for patients with clinical stage T1N0M0 (cT1N0M0) OSCC and whether up-front END improved survival. Patients and Methods: Patients with cT1N0M0 OSCC who underwent tumor resection with or without END were identified and extracted from the SEER database. Kaplan-Meier survival analysis was used to assess overall survival and disease-specific survival. Prognostic factors were determined using Cox regression analysis. Results: A total of 5,752 patients with cT1N0M0 OSCC were extracted, of whom 2,194 (38.1%) underwent tumor resection surgery with concurrent END and 3,558 (61.9%) underwent only tumor resection. In a multivariate Cox analysis, a relatively advanced age (>62 years) and relatively high pathologic grade were the significant negative predictors, but married status (hazard ratio, 0.709; P=.006) and undergoing END (hazard ratio, 0.708; PConclusions: Patients with cT1N0M0 OSCC gain significant overall and disease-specific survival benefit from END.

Background: Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses. Objective: We investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is affected by ICS treatment. Methods: We investigated the pharmacogenetic effect of 10 single nucleotide polymorphisms (SNPs) selected from the literature, including SNPs previously associated with response to ICS (assessed by change in lung function or exacerbations) and novel asthma risk alleles involved in inflammatory pathways, within all adults with asthma from the Dutch population–based Rotterdam study with replication in the American GERA cohort. The interaction effects of the SNPs with ICS on the incidence of asthma exacerbations were assessed using hurdle models adjusting for age, sex, BMI, smoking and treatment step according to the GINA guidelines. Haplotype analyses were also conducted for the SNPs located on the same chromosome. Results: rs242941 (CRHR1) homozygotes for the minor allele (A) showed a significant, replicated increased risk for frequent exacerbations (RR = 6.11, P

Polygonum multiflorum Thunb (PMT), as a traditional Chinese herbal medicine, has been widely used in the prevention and treatment of aging-related diseases, including Alzheimer's disease, Parkinson's disease, hyperlipidemia, atherosclerosis and inflammation. However, the effect of PMT on the lifespan and its molecular mechanisms are still unclear. Here we found that 60% ethanol refined fraction (PMT-E) of Polygonum multiflorum Thunb at 50 μg mL−1, which contained two main bioactive compounds, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) and emodin-8-O-β-D-glucoside (EG), could significantly increase the mean lifespan by 19.82%, delay the age-related decline of phenotypes, enhance stress resistance and reduce ROS accumulation in Caenorhabditis elegans. Moreover, we also found that the mitochondrial membrane potential (ΔΨ) and ATP content of worms treated with 50 μg mL−1 PMT-E were obviously improved. Further mechanistic studies revealed that DAF-16, SIR-2.1 and SKN-1 transcription factors were required for PMT-E-mediated lifespan extension. Finally, we found that PMT-E could significantly inhibit the toxicity induced by β-amyloid (Aβ) in Aβ transgenic worms. Altogether, these findings laid the foundation for the use of Polygonum multiflorum Thunb to treat aging and age-related diseases.

Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.

This study aimed to determine the mechanism of isogeneic-induced pluripotent stem cells (iPSCs) homing to vascular transplants and their therapeutic effect on chronic allogeneic vasculopathy. We found that integrin β1 (Intgβ1) was the dominant integrin β unit in iPSCs that mediates the adhesion of circulatory and endothelial cells (ECs). Intgβ1 knockout or Intgβ1-siRNAs inhibit iPSC adhesion and migration across activated endothelial monolayers. The therapeutic effects of the following were examined: iPSCs, Intgβ1-knockout iPSCs, iPSCs transfected with Intgβ1-siRNAs or nontargeting siRNAs, iPSC-derived ECs, iPSC-derived ECs simultaneously overexpressing Intgα4 and Intgβ1, iPSCs precultured in endothelial medium for 3 days (endothelial-prone stem cells), primary aortic ECs, mouse embryonic fibroblasts, and phosphate-buffered saline (control). The cells were administered every 3 days for a period of 8 weeks. iPSCs, iPSCs transfected with nontargeting siRNAs, and endothelial-prone stem cells selectively homed on the luminal surface of the allografts, differentiated into ECs, and decreased neointimal proliferation. Through a single administration, we found that iPSCs trafficked to allograft lesions, differentiated into ECs within 1 week, and survived for 4-8 weeks. The therapeutic effect of a single administration was moderate. Thus, Intgβ1 and pluripotency are essential for iPSCs to treat allogeneic vasculopathy.

Stroke is the leading cause of death and adult disability worldwide. Mitochondrial dysfunction is one of the hallmarks of stroke-induced neuronal death, and maintaining mitochondrial function is essential in cell survival and neurological progress following ischemic stroke. Stem cell-mediated mitochondrial transfer represents an emerging therapeutic approach for ischemic stroke. Accumulating evidence suggests that mesenchymal stem cells (MSCs) can directly transfer healthy mitochondria to damaged cells, and rescue mitochondrial damage-provoked tissue degeneration. This review summarizes the research on MSCs-mediated mitochondrial transfer as a therapeutic strategy against ischemic stroke.

Here, we detected platelet extravasation from blood vessels in both mouse and human hepatocellular carcinoma (HCC) tissues. We show C‐X3‐C chemokine ligand 1 (CX3CL1) derived from HCC cells induces platelet infiltration through a CX3CR1/Syk/PI3K pathway and the infiltrated platelets promote the apoptosis of HCC cells. These findings confirm that platelets are important factors in tumor regulation., The mechanisms and biological functions of migrating platelets in cancer remain largely unknown. Here, we analyzed platelet infiltration in hepatocellular carcinoma. We detected platelet extravasation in both mouse and human HCC tissues. CX3CL1 directly induced platelet migration, and hypoxia enhanced platelet migration by upregulating CX3CL1 expression. Knocking down CX3CL1 in HCC cells reduced platelet migration in vitro, as well as infiltration of HCC tissue in an orthotopic HCC mouse model. Components of the CX3CR1/Syk/PI3K pathway were essential for CX3CL1‐induced platelet migration. Migrating platelets induced HCC cell apoptosis in vitro, as indicated by a reduced mitochondrial membrane potential and an increased percentage of apoptotic cells. In the orthotopic tumor implantation model, decreased platelet infiltration was associated with accelerated tumor growth. Taken together, our findings indicate that HCC cell‐derived CX3CL1 contributes to tumor infiltration by platelets, which in turn promotes apoptosis of HCC cells.

Ischemic stroke is one of the leading causes of death and long-term disability worldwide. As an important class of pervasive genes involved in many pathophysiological processes of ischemic stroke, non-coding RNAs (ncRNAs) have received attention in the past decades. ncRNAs are a class of functional RNAs that regulate gene expression in a post-transcriptional manner, and including microRNAs, long non-coding RNAs, and circular RNAs. Several studies have deciphered that ncRNAs have a key role in the ischemic stroke-induced neuroinflammation and cell death via different molecules and pathways. Thus, ncRNAs show great promise as novel molecular targets in ischemic stroke. In this article, we provide an updated review of the current state of our knowledge about the roles of different types of ncRNAs in neuroinflammation and cell death following ischemic stroke, which may facilitate the translation of ncRNAs research into clinical practice to improve the clinical outcome of stroke therapy.

As a common type of joint used in spatial grid structures, the tensile performance of bolt-sphere joints directly affects the safety of the spatial grid structure under fire. To study the tensile properties of the bolts in sphere joints under fire, the four sets of 36 bolt-sphere joints consist of M20, M24, M30, and M36 high-strength bolts were conducted in elevated temperature by steady-state test. Therefore, the tensile bearing capacity of the bolt-sphere joint was obtained under different elevated temperatures. Experimental results show the destroyed section of the bolt-sphere joint that occurs in the thread of the high-strength bolt at the intersection of the sphere because of the maximum concentration of stresses that occurred in areas of destruction. The brittle fracture of bolt-sphere joints happened when the temperature is below 400 ℃. As the temperature increased, the neck shrinkage of the damaged section of the bolt becomes more apparent, and the ductile failure of the bolt-sphere joint occurred. The stiffness and the bearing capacity of bolt-sphere joints decreased gradually as the temperature rose. Conversely, the ductility was gradually increasing. When the temperature was greater than 300 ℃, the stiffness and the bearing capacity of the bolts in sphere joint decreased rapidly. The bearing capacity reduction coefficient of the high-strength bolts with different diameters were next to the same at elevated temperatures. According to the experimental data, the formulas of the tensile bearing capacity reduction coefficient of bolt-sphere joints were obtained.

Objectives Carbapenem-resistant Enterobacteriaceae (CRE) are a major public-health threat. The most important mechanism of carbapenem resistance in CRE is carbapenemase production. Early identification of carbapenemase-producing Enterobacteriaceae (CPE) leads to improved clinical outcomes. This systematic review aimed to assess the accuracy and applicability of the modified Hodge test (MHT), the carbapenemase Nordmann–Poirel (Carba NP) test, the modified carbapenem inactivation method (mCIM) and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) for CPE detection. Methods The meta-analysis included pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic (SROC) curve and area under the curve (AUC). Results A total of 67 studies were included in the analysis. Pooled effect sizes (95% confidence interval) of the MHT, Carba NP, mCIM and MALDI-TOF/MS, respectively, were as follows: sensitivity, 92% (87–95%), 97% (94–98%), 99% (99–100%) and 99% (96–100%); specificity, 93% (86–97%), 100% (99–100%), 99% (96–100%) and 99% (96–100%); diagnostic odds ratio, 98.156 (48.175–199.995), 1277.710 (751.391–2172.692), 3597.352 (1287.575–10000) and 1781.360 (651.827–4868.228); and AUC, 0.97, 1, 1 and 1. Conclusion Carba NP, mCIM and MALDI-TOF/MS all demonstrated high accuracy in CPE detection, whereas the MHT is not recommended owing to some clear drawbacks. We recommend the selection of carbapenemase detection tests in the order of mCIM, Carba NP and MALDI-TOF/MS according to their simplicity, cost, and equipment and skills involved.

Mitochondrial dysfunction has long been implicated in the neurodegenerative disorder Parkinson's disease (PD); however, it is unclear how mitochondrial impairment and α-synuclein pathology are coupled. Using specific mitochondrial inhibitors, EM analysis, and biochemical assays, we report here that intramitochondrial protein homeostasis plays a major role in α-synuclein aggregation. We found that interference with intramitochondrial proteases, such as HtrA2 and Lon protease, and mitochondrial protein import significantly aggravates α-synuclein seeding. In contrast, direct inhibition of mitochondrial complex I, an increase in intracellular calcium concentration, or formation of reactive oxygen species, all of which have been associated with mitochondrial stress, did not affect α-synuclein pathology. We further demonstrate that similar mechanisms are involved in amyloid-β 1-42 (Aβ42) aggregation. Our results suggest that, in addition to other protein quality control pathways, such as the ubiquitin-proteasome system, mitochondria per se can influence protein homeostasis of cytosolic aggregation-prone proteins. We propose that approaches that seek to maintain mitochondrial fitness, rather than target downstream mitochondrial dysfunction, may aid in the search for therapeutic strategies to manage PD and related neuropathologies.

Purpose Little is known about the epidemiology and carbapenem-resistance determinants of carbapenem-resistant K. aerogenes (CRKA) isolated from a single medical center. The present study was initiated to characterize the molecular epidemiology and the carbapenem-resistance mechanisms of CRKA isolated during 2012-2018 from a teaching hospital in southwest China, and to investigate the risk factors and clinical outcomes of CRKA infections as well. Methods Pulsed-field gel electrophoresis (PFGE) was employed for epidemiological analysis. PCR amplification and DNA sequencing were used to examine the antibiotic-resistance determinants. Plasmids were extracted and characterized by PCR-based replicon typing and conjugation assays. In order to further investigate the risk factors and clinical outcomes of CRKA infections, a retrospective case-control study was also performed. Results PFGE analysis showed 32 different PFGE patterns among the 36 non-duplicated CRKA strains collected. Most of the isolates harbored multi-drug resistance (MDR) genes, including 2 (5.6%) carrying bla NDM-1, 1 (2.8%) harboring bla KPC-2, 13 (36.1%) carrying ESBL genes, 23 (63.9%) carrying ampC genes, 34 (94.4%) carrying quinolone resistance determinants (QRD) genes and 9 (25%) carrying aminoglycoside resistance determinants (ARD) genes. The outer membrane porins, OmpE35 and OmpE36, were, respectively, lost in 4 and 2 isolates. The efflux pump inhibition experiments were positive in 25 (69.4%) of the CRKA strains. Multivariate analysis indicated that hypo-albuminaemia, invasive procedures, and carbapenem exposure were independent risk factors for acquiring CRKA infections. Conclusion No clonality relationship was identified among most of the 36 CRKA isolates. The over-expression of ESBLs and AmpC coupled with the efflux pumps contributed to carbapenem resistance in K. aerogenes. Additionally, this is the first report of CRKA isolate co-harboring bla NDM-1, bla CTX-M-15, bla EBC, bla ACC, acc (6')-Ib, armA, qnrD and loss of OmpE36 in China. Hypo-albuminaemia, invasive procedures and carbapenem exposure were associated with acquisition of CRKA infections.

The structural modification of polysaccharides directly affects their physicochemical properties and applications. Dextran, a chained polysaccharide, consists of multiple d -glucose molecules with repetitive structures. In this study, the physicochemical properties of oxidized dextran (DO) at different concentrations of NaClO/NaBr and H2O2 were compared. The results showed that NaClO/NaBr oxidation is more conducive to the formation of carboxyl groups. Oxidized dextran with NaClO/NaBr (DOB) showed good iron (III) chelating ability, and the DOB‑iron (III) complex (DOBIC) had an iron content of 28.31%. According to structural analysis, NaClO/NaBr (2 g/100 g of active chlorine) and H2O2 (4 g/100 g), respectively, oxidize the C1 and C2 hydroxyl groups of dextran to carboxyl groups and open the ring when DO and iron have the strongest chelation ability. The complex is indeed a chelate iron complex, and iron core is composed of iron oxyhydroxide or the β-FeOOH mineral polymorph. These results indicate that DOBIC is expected to be a good iron supplement or food additive to strengthen iron.

Background: Diabetes increases the risk for various cancers without established mechanisms. Centrosome amplification can initiate tumorigenesis in genetically modified cells. However, the findings from genetically modified experimental models may be far away from reality. We have reported that diabetes promotes the occurrence of centrosome amplification in different types of cells, implicating that centrosome amplification is a candidate mechanism underlying the diabetes-promoted tumorigenesis. In the present study, we investigated the molecular mechanisms of the centrosome amplification triggered by high glucose, insulin and palmitic acid using HCT116 colon cancer cells as an experimental model. Results: We found that KIF2A was localized in the centrosomes. The experimental treatment induced the binding between ROCK1 and KIF2A, although did not increase the protein level of KIF2A. The molecular docking modeling analysis also showed that the two proteins had the binding/interaction potential. We used siRNA of each protein to knockdown their expression level, as a tool to disrupt the ROCK1-KIF2A complex, which attenuated the treatment-induced centrosome amplification. Conclusions: Our results suggest that the binding between ROCK1 and KIF2A signals for the diabetes-associated centrosome amplification. This provides a molecular target for the inhibition of the centrosome amplification, which might be required for assessing the role of centrosome amplification in cancer in the nature, such as cancer in diabetes.

A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY., Normally, norepinephrine (NE) and acetylcholine (ACh) production is maintained at a balanced level in bone, so that osteocytes cannot generate excessive neuropeptide Y (NPY) to favor bone marrow mesenchymal stem/stromal cell adipogenesis rather than osteogenesis. With aging/estrogen deficiency, sympathetic overactivity, and decreased parasympathetic activity cause NE overproduction and ACh reduction, resulting in excess osteocyte NPY generation and subsequent bone‐fat imbalance.

Pengfei Sun, Meng Lu, Changchen Wang, Bo Pan Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People’s Republic of ChinaCorrespondence: Bo PanDepartment of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 33 Badachu Road, Shijingshan District, Beijing, 100144, People’s Republic of ChinaTel +8613810855912Email zbzbzhc@163.comPurpose: This study evaluated the utility of a ruler for reconstructed article positioning.Methods: Forty-seven patients with unilateral microtia were selected from August 2020 to September 2021.Results: The linear distance from the highest point of the reconstructed auricle to the central axis of the nose was not significantly different from the distance from the highest point of the normal contralateral auricle to the central axis of the nose (P> 0.05). The distance from the lowest point of the reconstructed auricle to the central axis of the nose was not significantly different from the distance from the lowest point of the normal auricle to the central axis of the nose (P> 0.05). The linear distance from the highest to the lowest point of the reconstructed auricle was not significantly different from the distance from the highest to the lowest point of the normal auricle (P> 0.05). These results indicate that the reconstructed auricle was symmetrical to the contralateral ear.Conclusion: The positioning ruler evaluated in this study is simple, easy to use, accurate, and non-invasive.Keywords: microtia, reconstructed auricle, ruler, ear

Rheumatoid arthritis (RA) is a classic autoimmune disease characterized by uncontrolled synovial proliferation, pannus formation, cartilage injury, and bone destruction. The specific pathogenesis of RA, a chronic inflammatory disease, remains unclear. However, both key glycolysis rate-limiting enzymes, hexokinase-II (HK-II), phosphofructokinase-1 (PFK-1), and pyruvate kinase M2 (PKM2), as well as indirect rate-limiting enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), are thought to participate in the pathogenesis of RA. In here, we review the latest literature on the pathogenesis of RA, introduce the pathophysiological characteristics of HK-II, PFK-1/PFKFB3, and PKM2 and their expression characteristics in this autoimmune disease, and systematically assess the association between the glycolytic rate-limiting enzymes and RA from a molecular level. Moreover, we highlight HK-II, PFK-1/PFKFB3, and PKM2 as potential targets for the clinical treatment of RA. There is great potential to develop new anti-rheumatic therapies through safe inhibition or overexpression of glycolysis rate-limiting enzymes.

Background Long QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within‐person QT change over time in relation to risk of incident CVD and all‐cause mortality in a real‐world setting. Methods and Results A cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non‐White) with 3 or more ECGs (baseline in 2005–2009; mean±SD follow‐up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all‐cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all‐cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all‐cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07). Conclusions Our results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long‐term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.