Gastrointestinal trichobezoars in the pediatric population: a retrospective study.

BACKGROUND: Trichobezoar is an extremely rare condition characterized by a foreign body in the gastrointestinal tract (GIT) among children. The foreign body may exist in the digestive tract for several years, and it becomes evident if complications develop. The current study aimed to present 21 cases of GIT trichobezoars. METHODS: Retrospective analysis of children who were diagnosed with trichobezoars between August 2012 and December 2022. Patient demographics, clinical presentation, diagnosis, and therapy were collected and analyzed.Twenty-one patients had GIT trichobezoars. Data were collected and analyzed retrospectively. RESULTS: Twenty-one patients were identified. All patients were female. Their mean age at admission was 8.9 ± 1.9 years. Furthermore, 19 (90.5%) patients presented with abdominal pain, 16 (76.2%) with vomiting, and 13 (61.9%) with a palpable mass. Sixteen patients underwent gastroduodenoscopy. Among them, 15 had gastric trichobezoars. Moreover, 12 patients underwent computed tomography scan. Eight patients presented with gastric and small intestinal BZs, one presented with increased small intestinal contents with dilation, and one presented with abundant gastric contents. Then, 20 patients underwent surgery. Among them, five underwent laparoscopic-assisted minilaparotomy (LAML), and the rest underwent laparotomy. The results showed that 10 (50%) patients had gastric trichobezoars; 7 (35%), Rapunzel syndrome; and 3 (15%), small bowel trichobezoars. Two patients developed superficial wound infection postoperatively. One patient had a recurrent gastric trichobezoar. CONCLUSION: Trichobezoar should be considered in young girls with a history of hair eating or those with hair in the vomit or feces. Timely diagnosis and aggressive treatment are the keys to reducing complications and improving prognosis. Laparoscopic-assisted minilaparotomy is a safe, feasible, and effective surgical method for treating trichobezoars.

Deep learning-based semantic segmentation of non-melanocytic skin tumors in whole-slide histopathological images.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two most common skin cancer and impose a huge medical burden on society. Histopathological examination based on whole-slide images (WSIs) remains to be the confirmatory diagnostic method for skin tumors. Accurate segmentation of tumor tissue in WSIs by deep-learning (DL) models can reduce the workload of pathologists and help surgeons ensure the complete removal of tumors. To accurately segment the tumor areas in WSIs of BCC, SCC and squamous cell papilloma (SCP, homologous to SCC) with robust models. We established a data set (ZJU-NMSC) containing 151 WSIs of BCC, SCC and SCP in total. Seven models were utilized to segment WSIs, including the state-of-the-art model, models proposed by us and other models. Dice score, intersection over union, accuracy, sensitivity and specificity were used to evaluate and compare the performance of different models. Heatmaps and tumor tissue masks were generated to reflect the results of the segmentation. The processing times of models are also recorded and compared. While the dice score of most models is higher than 0.85, deeplab v3+ has the best performance and the corresponding tumor tissue mask is more consistent with the ground truth tumor areas even with complex and small lobular lesions. This study broadens the use of DL-based segmentation models in WSIs of skin tumors in terms of tumor types and computational approaches. Segmenting tumor areas can simplify the process of histopathological inspection and benefit the diagnosis and following management of the diseases in practice.

Nkx2-5 defines a subpopulation of pacemaker cells and is essential for the physiological function of the sinoatrial node in mice.

The sinoatrial node (SAN), the primary cardiac pacemaker, consists of a head domain and a junction/tail domain that exhibit different functional properties. However, the underlying molecular mechanism defining these two pacemaker domains remains elusive. Nkx2-5 is a key transcription factor essential for the formation of the working myocardium, but it was generally thought to be detrimental to SAN development. However, Nkx2-5 is expressed in the developing SAN junction, suggesting a role for Nkx2-5 in SAN junction development and function. In this study, we present unambiguous evidence that SAN junction cells exhibit unique action potential configurations intermediate to those manifested by the SAN head and the surrounding atrial cells, suggesting a specific role for the junction cells in impulse generation and in SAN-atrial exit conduction. Single-cell RNA-seq analyses support this concept. Although Nkx2-5 inactivation in the SAN junction did not cause a malformed SAN at birth, the mutant mice manifested sinus node dysfunction. Thus, Nkx2-5 defines a population of pacemaker cells in the transitional zone. Despite Nkx2-5 being dispensable for SAN morphogenesis during embryogenesis, its deletion hampers atrial activation by the pacemaker.

Nanocrystalline Cubic Silicon Carbide: A Route to Superhardness.

Superhard materials other than diamond and cubic boron nitride have been actively pursued in the past two decades. Cubic silicon carbide, i.e., ß-SiC, is a well-known hard material with typical hardness <30 GPa. Although nanostructuring has been proven to be effective in enhancing materials' hardness by virtue of the Hall-Petch effect, it remains a significant challenge to improve hardness of ß-SiC beyond the superhard threshold of 40 GPa. Here, the fabrication of nanocrystalline ß-SiC bulks is reported by sintering nanoparticles under high pressure and high temperature. These ß-SiC bulks are densely sintered with average grain sizes down to 10 nm depending on the sintering conditions, and the Vickers hardness increases with decreasing grain size following the Hall-Petch relation. Particularly, the bulk sintered under 25 GPa and 1400 °C shows an average grain size of 10 nm and an asymptotic Vickers hardness of 41.5 GPa. Boosting the hardness of ß-SiC over the superhard threshold signifies an important progress in superhard materials research. A broader family of superhard materials is in sight through successful implementation of nanostructuring in other hard materials such as BP.

Efficacy of Care and Antibiotic Use for Chalazia and Hordeola.

OBJECTIVES: To evaluate whether use of an antibiotic improves the efficacy of care for a chalazion or hordeolum. METHODS: A cross-sectional retrospective review was performed. All patients treated for a newly diagnosed chalazion or hordeolum at the University of California, San Francisco from 2012 to 2018 were identified. Patients were excluded when clinical notes were inaccessible or there was inadequate documentation of treatment modality or outcome. Patient demographics, setting of initial presentation, treatment modalities, antibiotic use, and outcomes were analyzed. RESULTS: A total of 2,712 patients met inclusion criteria. Management with an antibiotic was observed in 36.5% of patients. An antibiotic was 1.53 times (95% confidence interval [CI], 1.06-2.22, P=0.025) more likely to be prescribed in emergency or acute care setting for a chalazion. Older age was associated with a higher risk of receiving an antibiotic for a hordeolum (adjusted RR 1.07 per decade, 95% CI, 1.05-1.11, P<0.001). The addition of an antibiotic to conservative measures for a chalazion (adjusted RR, 0.97, 95% CI, 0.89-1.04, P=0.393) or hordeolum (adjusted RR, 0.99, 95% CI, 0.96-1.02, P=0.489) was not associated with an increased likelihood of treatment success. CONCLUSION: Although frequently prescribed, an antibiotic is unlikely to improve the resolution of a chalazion or hordeolum.

Toward a better understanding of nonoccupational sound exposures and associated health impacts: Methods of the Apple Hearing Study.

Globally, noise exposure from occupational and nonoccupational sources is common, and, as a result, noise-induced hearing loss affects tens of millions of people. Occupational noise exposures have been studied and regulated for decades, but nonoccupational sound exposures are not well understood. The nationwide Apple Hearing Study, launched using the Apple research app in November 2019 (Apple Inc., Cupertino, CA), is characterizing the levels at which participants listen to headphone audio content, as well as their listening habits. This paper describes the methods of the study, which collects data from several types of hearing tests and uses the Apple Watch noise app to measure environmental sound levels and cardiovascular metrics. Participants, all of whom have consented to participate and share their data, have already contributed nearly 300 × 106 h of sound measurements and 200 000 hearing assessments. The preliminary results indicate that environmental sound levels have been higher, on average, than headphone audio, about 10% of the participants have a diagnosed hearing loss, and nearly 20% of the participants have hearing difficulty. The study's analyses will promote understanding of the overall exposures to sound and associated impacts on hearing and cardiovascular health. This study also demonstrates the feasibility of collecting clinically relevant exposure and health data outside of traditional research settings.

Chemical Composition, Antitumor Properties, and Mechanism of the Essential Oil from Plagiomnium acutum T. Kop.

Plagiomnium acutum T. Kop. (P. acutum) has been used as a traditional Chinese medicine for thousands of years to treat cancer but lacks evidence. The objective of this work was to reveal the chemical composition of P. acutum essential oil (PEO) and explore its potential antitumor activity and molecular mechanism. PEO was prepared by the simultaneous distillation-extraction method and characterized by gas chromatography/mass spectroscopy. CCK8 assay, flow cytometry, western blot, and immunofluorescence techniques were used to analyze the effects and mechanism of PEO against cancer cells. A total of 74 constituents of PEO were identified, with diterpenes (26.5%), sesquiterpenes (23.89%), and alcohols (21.81%) being the major constituents. Two terpenoids, selina-6-en-4-ol and dolabella-3,7-dien-18-ol, were detected in PEO for the first time. PEO showed significant cell growth inhibitory activity on HepG2 and A549 cells by blocking the G1 phase and inducing apoptosis, which may be attributed to its upregulation of p21Cip1 and p27Kip1 proteins and interference with mitochondrial membrane potential effect. Dolabella-3,7-dien-18-ol accounts for 25.5% of PEO and is one of the main active components of PEO, with IC50 values in HepG2 and A549 cells of (25.820 ± 0.216) µg/mL and (23.597 ± 1.207) µg/mL, respectively. These results confirmed the antitumor medicinal value of P. acutum and showed great application potential in the pharmaceutical industry.

Conjugated activation of myocardial-specific transcription of Gja5 by a pair of Nkx2-5-Shox2 co-responsive elements.

The sinoatrial node (SAN) is the primary pacemaker in the heart. During cardiogenesis, Shox2 and Nkx2-5 are co-expressed in the junction domain of the SAN and regulate pacemaker cell fate through a Shox2-Nkx2-5 antagonism. Cx40 is a marker of working myocardium and an Nkx2-5 transcriptional output antagonized by Shox2, but the underlying regulatory mechanisms remain elusive. Here we characterized a bona fide myocardial-specific Gja5 (coding gene of Cx40) distal enhancer consisting of a pair of Nkx2-5 and Shox2 co-bound elements in the regulatory region of Gja5. Transgenic reporter assays revealed that neither element alone, but the conjugation of both elements together, drives myocardial-specific transcription. Genetic analyses confirmed that the activation of this enhancer depends on Nkx2-5 but is inhibited by Shox2 in vivo, and its presence is essential for Gja5 expression in the myocardium but not the endothelial cells of the heart. Furthermore, chromatin conformation analysis showed an Nkx2-5-dependent loop formation between these two elements and the Gja5 promoter in vivo, indicating that Nkx2-5 bridges the conjugated activation of this enhancer by pairing the two elements to the Gja5 promoter.

The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice.

Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre -mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre ;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis.

Shox2 regulates osteogenic differentiation and pattern formation during hard palate development in mice.

During mammalian palatogenesis, cranial neural crest-derived mesenchymal cells undergo osteogenic differentiation and form the hard palate, which is divided into palatine process of the maxilla and the palatine. However, it remains unknown whether these bony structures originate from the same cell lineage and how the hard palate is patterned at the molecular level. Using mice, here we report that deficiency in Shox2 (short stature homeobox 2), a transcriptional regulator whose expression is restricted to the anterior palatal mesenchyme, leads to a defective palatine process of the maxilla but does not affect the palatine. Shox2 overexpression in palatal mesenchyme resulted in a hyperplastic palatine process of the maxilla and a hypoplastic palatine. RNA sequencing and assay for transposase-accessible chromatin-sequencing analyses revealed that Shox2 controls the expression of pattern specification and skeletogenic genes associated with accessible chromatin in the anterior palate. This highlighted a lineage-autonomous function of Shox2 in patterning and osteogenesis of the hard palate. H3K27ac ChIP-Seq and transient transgenic enhancer assays revealed that Shox2 binds distal-acting cis-regulatory elements in an anterior palate-specific manner. Our results suggest that the palatine process of the maxilla and palatine arise from different cell lineages and differ in ossification mechanisms. Shox2 evidently controls osteogenesis of a cell lineage and contributes to the palatine process of the maxilla by interacting with distal cis-regulatory elements to regulate skeletogenic gene expression and to pattern the hard palate. Genome-wide Shox2 occupancy in the developing palate may provide a marker for identifying active anterior palate-specific gene enhancers.

Exogenous FGF8 signaling in osteocytes leads to mandibular hypoplasia in mice.

OBJECTIVE: Fibroblast growth factor 8 (FGF8) signaling is essential in regulating craniofacial osteogenesis. This study aims to explore the effect of altered FGF8 signaling in maxillomandibular development during embryogenesis. MATERIALS AND METHODS: Dmp1Cre ;R26RmTmG mice were generated to trace Dmp1+ cell lineage, and Dmp1Cre ;R26RFgf8 mice were generated to explore the effects of augmented FGF8 signaling in Dmp1+ cells on osteogenesis with a focus on maxillomandibular development during embryogenesis, as assessed by whole mount skeletal staining, histology, and immunostaining. Additionally, cell proliferation rate and the expression of osteogenic genes were examined. RESULTS: Osteocytes of maxillomandibular bones were found Dmp1-positive prenatally, and Fgf8 over-expression in Dmp1+ cells led to mandibular hypoplasia. While Dmp1Cre allele functions in the osteocytes of the developing mandibular bone at as early as E13.5, and enhanced cell proliferation rate is observed in the bone forming region of the mandible in Dmp1Cre ;R26RFgf8 mice at E14.5, histological examination showed that osteogenesis was initially impacted at E15.5, along with an inhibition of osteogenic differentiation markers. CONCLUSIONS: Augmented FGF8 signaling in Dmp1+ cells lead to osteogenic deficiency in the mandibular bones, resulting in mandibular hypoplasia.

Values of integration between lipidomics and clinical phenomes in patients with acute lung infection, pulmonary embolism, or acute exacerbation of chronic pulmonary diseases: a preliminary study.

BACKGROUND: The morbidity and mortality of patients with critical illnesses remain high in pulmonary critical care units and a poorly understood correlation between alterations of lipid elements and clinical phenomes remain unelucidated. METHODS: In the present study, we investigated plasma lipidomic profiles of 30 patients with severe acute pneumonia (SAP), acute pulmonary embolism (APE), and acute exacerbation of chronic pulmonary diseases (AECOPD) or 15 healthy with the aim to compare disease specificity of lipidomic patterns. We defined the specificity of lipidomic profiles in SAP by comparing it to both APE and AECOPD. Analysis of the correlation between altered lipid elements and clinical phenotypes using the lipid-QTL model was then carried out. RESULTS: We integrated lipidomic profiles with clinical phenomes measured by score values from the digital evaluation score system and found phenome-associated lipid elements to identify disease-specific lipidomic profiling. The present study demonstrates that lipidomic profiles of patients with acute lung diseases are different from healthy lungs, and there are also disease-specific portions of lipidomics among SAP, APE, or AECOPD. The comprehensive profiles of clinical phenomes or lipidomics are valuable in describing the disease specificity of patient phenomes and lipid elements. The combination of clinical phenomes with lipidomic profiles provides more detailed disease-specific information on panels of lipid elements When compared to the use of each separately. CONCLUSIONS: Integrating biological functions with disease specificity, we believe that clinical lipidomics may create a new alternative way to understand lipid-associated mechanisms of critical illnesses and develop a new category of disease-specific biomarkers and therapeutic targets.

Theoretical investigation of the valence states in Au via the Au-F compounds under high pressure.

In addition to the known Au3+ and Au5+, it has recently been shown that Au is likely to possess unusual valence states in compressed Au-F compounds. However, our simulations reveal that polymeric ground-state AuF4 shows an unexpected 6-fold coordination rather than a 4-fold one, indicating that more complete comprehending on the anomalous Au4+ is highly required. To fully understand the nature and origin of anomalous valence states in Au, we have extensively investigated the ground-state structures of Au-F compounds at high pressures using quantum mechanical computational methods. As a consequence, we identify several previously unreported (stable) AuF2, AuF3 and AuF4 structures. Our results extend the known polymorphism of AuFn compounds and offer a fundamental understanding of the origin of unusual valence states in Au that prevail at high pressure.

[Clinical analysis of annular pancreas in neonates].

OBJECTIVE: To analyze clinical manifestations, diagnosis and treatment of annular pancreas in neonates. METHODS: Clinical data of 114 neonates with annular pancreas admitted in the Children's Hospital of Zhejiang University from January 2009 to December 2018 were reviewed. The demographic parameters (gestational age, birth weight), clinical manifestations, onset time, results of antenatal examination, associated anomalies, radiological findings, operations, postoperative complications were analyzed. RESULTS: One hundred and two cases were examined by abdominal echography, in which 68 cases showed duodenal obstruction, 4 cases showed annular pancreas. Plain abdomen X-ray examination performed in 113 cases before operation, 76 cases presented double-bubble sign, 12 cases presented single-bubble sign and 5 cases had high-position intestinal obstruction. Upper gastrointestinal radiography (UGI) was performed in 103 cases, which suggested duodenal obstruction in 102 cases. Operations were performed in all cases, of which 69 cases were operated under laparoscopy including 1 case converted to open laparotomy. The mean fasting time after surgery was (7.8±2.7) d, and the mean length of hospital stay was (16.9±10.1) d. Five patients had postoperative complications. The incidence of postoperative complications in antenatal abnormal group was lower than that in the antenatal non-abnormal group (P<0.05); the average fasting time in laparoendscopic surgery group was shorter than that in traditional laparotomy group (P<0.05). CONCLUSIONS: Neonates with recurrent vomiting early after birth should be highly suspected to have annular pancreas. The fetal chromosome examination should be performed with abnormal antenatal screening. Surgery is the only effective way to diagnose and treat annular pancreas, and laparoscopic surgery could be the first choice for experienced doctors.

New strategies for targeting drug combinations to overcome mutation-driven drug resistance.

Targeted therapies are suggested as an effective alternative for patients with cancer that harbor mutations, but treatment outcomes are frequently limited by primary or acquired drug resistance. The present review describes potential mechanisms of primary or acquired drug resistances to provide a resource for considering how to be overcome. We focus on strategies of targeted drug combinations to minimize the development of drug resistance within the context how resistance develops. Strategies benefit from the combined use of "omics" technologies, i.e., high-throughput functional genomics data, pharmacogenomics, or genome-wide CRISPR-Cas9 screening, to analyze and design targeted drug combinations for mutation-driven drug resistance. We also introduce new insights towards pathway-centric combined therapies as an alternative to overcome the heterogeneity and benefit patient prognoses.

Effect of cyclic uniaxial compressive stress on human dental pulp cells in vitro.

PURPOSE: Teeth are exposed to various forces during functional and parafunctional movements. These processes inevitably affect the dental pulp, and the mechanism of these influences has been the subject of many previous studies using different apparatuses and obtaining different results. In this study, we aimed to investigate the effects of compressive stress on the proliferation and differentiation of human dental pulp cells (hDPCs). MATERIALS AND METHODS: A four-point bending strain system was adopted to apply low-density cyclic uniaxial compressive stress (2000 microstrain, 0.5 Hz) to hDPCs for 1.5, 3, 6, 12, and 24 h. The cell cycle progression and mRNA expression of differentiation-related genes (BMP2, ALP, DMP1, DSPP, COL I) were then examined to investigate the proliferation and differentiation of hDPCs. RESULTS: The results showed that cyclic compressive stress changed the morphology of hDPCs after 12 and 24 h of mechanical loading; cell cycle progression was promoted, especially in the 24-h group (p < 0.05). The expression of BMP2 was significantly upregulated after 3 and 6 h of mechanical loading but declined in the 12- and 24-h groups, whereas the expression levels of DMP1 and DSPP were significantly upregulated in the 12- and 24-h loading groups (p < 0.05). CONCLUSIONS: Dental pulp cells were sensitive to compressive stress, especially after 12 and 24 h of applied force. Proliferation and odontogenic differentiation were significantly promoted in this in vitro model.

The mechanism of roughness-induced CO2 microbubble nucleation in polypropylene foaming.

Within the framework of classical density functional theory, the thermodynamic driving forces for CO2 microbubble nucleation have been quantitatively evaluated in the foaming of polypropylene containing amorphous and crystalline structures. After the addition of fluorinated polyhedral oligomeric silsesquioxane particles into the polypropylene matrix, we construct different composite surfaces with nanoscale roughness for bubble nucleation. Meanwhile, as the dissolved CO2 molecules increase, the corresponding CO2/PP binary melts can be formulated in the systems. Due to the roughness effect coupled with the weak interactions of particle-PP, PP chains in the binary melts are depleted from the surfaces, leading to a significant enhancement of osmotic pressure in depletion regions. During the foaming process, a large number of dissolved CO2 molecules are squeezed into the regions, thus local supersaturations are dramatically improved, and the energy barriers for bubble nucleation are dramatically reduced. Moreover, when the nanocomposite surfaces display ordered nanoscale patterns, the energy barriers can be further reduced to their respective minimum values, and the bubble number densities reach their maximum. Accordingly, the bubble number densities can be enhanced by 4 or 5 orders of magnitude for bubbles nucleated on the crystalline or amorphous PP nanocomposite surface. In contrast, when the foaming pressure is increased from 15 to 20 MPa, the elevated bubble number density in the foaming PP matrix is less than one order of magnitude. As a result, the enhancement of local supersaturation induced by the controlled nanoscale roughness is much more effective than that of bulk supersaturation given by high pressure.

[Preparation and in vitro evaluation of rhein-loaded PEG-PCL-PEI nanoparticles].

This study was aimed to synthesize the polyethyleneglycol-polycaprolactone-polyethyleneimine (PEG-PCL-PEI) three block polymer material, prepareRhein (RH)-loaded PEG-PCL-PEI nanoparticles(PPP-RH-NPS), and then evaluate their physical and chemical properties and biological characteristics in vitro. PEG-PCL-PEI polymer was obtained by adopting thering-opening polymerization and Michael addition reaction, and their physical and chemical properties were analyzed by using NMR and gel permeation chromatography. PEG-PCL-PEI was then used as the carriers to prepare PPP-RH-NPS by applying spontaneous emulsification solvent diffusion method. The results showed that molecular weight of PEG-PCL-PEI polymer was 9.5×103, and critical micelle concentration was 0.723 mmol•L⁻¹. PPP-RH-NPS had pale yellow, opalescence faade, round and smooth without aggregation, formed of (118.3±3.6) nm in particle size with PDI of (0.19±0.08), Zeta potential of (6.3±1.5) mV, entrapment efficiency of (93.64±5.28)%, and drug loading of (8.57±0.53)%. The accumulative release percentage of PPP-RH-NPS was 75.92% in 48h, and the release profiles in PBS conformed to the Higuchi equation： Q=0.121 6t1/2+0.069 5 (R²=0.887 4), presenting slow release characteristics. Within the scope of the 0-0.05 mmol•L⁻¹, the nanoparticles had no obvious hemolysis on rabbit red blood cells and toxicity on HK-2 cells. In the investigation of uptake efficiency by flow cytometry, nanoparticles can be absorbed into cells quickly and internalized within 30 minutes fully, with a high uptake efficiency. In confocal laser scanning microscope observation, the nanoparticles can escape from lysosome into cytoplasm. Herein, this study synthesized the PEG-PCL-PEI polymer and prepared PPP-RH-NPS successfully; the nanoparticles showed uniform particle size, higher encapsulation efficiency and drug-loading rate, slow release characteristics, quick uptake and internalization, lysosome escape property and good biocompatibility. PPP-RH-NPS will be a promising pharmaceutical formulation for further development.

Glycometabolic reprogramming associated with the initiation of human dental pulp stem cell differentiation.

Glycometabolism, particularly mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, plays a central role in cell life activities. Glycometabolism can be reprogrammed to maintain the stemness or to induce the differentiation of stem cells, thereby regulating tissue repair and regeneration. However, research on the glycometabolism of human dental pulp stem cells (hDPSCs) remains scarce. Here, we investigated the relationship between glycometabolic reprogramming and initiation of hDPSC differentiation. We found the differentiation of hDPSCs commenced on day 3 when cells were cultured in mineralized medium. When cell differentiation commenced, mitochondria became elongated with well-developed cristae, and the oxygen consumption rate of mitochondria was enhanced, manifested as an increase in basal respiration, mitochondrial ATP production, and maximal respiration. Interestingly, glycolytic enzyme activities, glycolysis capacity, and glycolysis reserve were also upregulated at this time to match the powerful bioenergetic demands. More importantly, hDPSCs derived from different donors or cultured in various oxygen environments showed similar glycometabolic changes when they began to differentiate. Thus, glycometabolic reprogramming accompanies initiation of hDPSC differentiation and could potentially play a role in the regulation of dental pulp repair.