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Summary The safety, quantitative method and delivery of faecal microbiota transplantation (FMT) vary a lot from different countries in practice. Recently, the improved methodology of FMT based on the automatic filtration, washing process and the related delivery was named as washed microbiota transplantation (WMT). First, this study aimed to describe the methodology development of FMT from manual to washing preparation from 2012 to 2021 in China Microbiota Transplantation System (CMTS), a centralized stool bank for providing a national non‐profit service. The secondary aim is to describe donor screenings, the correlation between faecal weight and treatment doses, incidence of adverse events and delivery decision. The retrospective analysis on the prospectively recorded data was performed. Results showed that the success rate of donor screening was 3.1% (32/1036). The incidence rate of fever decreased significantly from 19.4% (6/31) in manual FMT to 2.7% (24/902) in WMT in patients with ulcerative colitis (UC), which made UC a considerable disease model to reflect the quality control of faecal microbiota preparation. We defined one treatment unit as 10 cm3 microbiota precipitation (1.0 × 1013 bacteria) based on enriched microbiota instead of rough faecal weight. For delivering microbiota, colonic transendoscopic enteral tube is a promising way especially for multiple WMTs or frequent colonic administration of drugs combined with WMT. This study should help improve the better practice of FMT for helping more patients in the future.

The microtubule plus-end tracking protein Tip1 regulates microtubule dynamics and polar growth in fission yeast. Here the authors link the ubiquitination of Tip1 by ubiquitin ligase Dma1 to polarized growth inhibition upon DNA replication stress.

As a kind of hazardous solid waste, the resource utilization of secondary aluminum ash (SAA) has become a worldwide challenge. The powdered Al and AlN contained in SAA will release a significant amount of heat during thermal treatment, making SAA have the potential to be used as a secondary energy resource. The thermogravimetric analysis (TG/DTG) coupled to a Fourier transform infrared spectrometer (FTIR) was carried out to evaluate the thermal degradation behavior and thermodynamic of SAA from room temperature to 1300 °C at three different heating rates (5, 10, 20 °C/min). The activation energy was calculated by model-free methods, showing that the activation energy of SAA during pyrolysis ranged from 39.99 to 552.3 kJ/mol for conversion rate (α) = 0.1–0.4. The FTIR results displayed gas products including O–H, C–H, N–H, and N=O groups. The increase in temperature from 1100 °C to 1500 °C will make the phase intensity of chloride and AlN gradually decrease, while the Al2O3 is opposite. However, submicron-sized aggregates can still be observed in the sintered samples at 1100 °C and 1200 °C. After calcination at 1500 °C for 3 h, the micro morphology of SAA is basically dominated by large granular Al2O3 and spinel, which verifies the possibility of slag as the raw material for ceramics and refractories. This research provides a novel idea of employing SAA as a secondary energy resource as well as the theoretical basis data on thermodynamics.

In this study, based on a closed bomb test combined with computational fluid dynamics, a structural finite element method, and an acoustic boundary element method, a fluid-solid acoustic one-way coupling calculation model is established for the combustion process of energetic materials in a closed bomb, and the effectiveness of the model is verified by experiments. It is found that the maximum peak sound pressure increases exponentially with an increase in loading doses or gas pressure. However, a change in the combustion coefficient of the energetic materials has little effect on the noise generated during the combustion process in the closed bomb. When the combustion coefficient is reduced by a multiple of 16, the maximum transient sound pressure is reduced by 1.79 dB, and the sound pressure level in the frequency band is reduced by 1.75 dB. With an increase in shell thickness, the combustion noise of the energetic materials in the closed bomb decreases, and the reduction range of the combustion noise increases with the increase in shell thickness.

Background: Cyclophosphamide (CTX) is the first-line medication for the treatment of breast cancer, although it potentially leads to severe ovarian dysfunction and even premature ovarian failure (POF). However, the mechanism of CTX-induced POF remains unclear. Mesenchymal stem cell-based therapy has been wildly used for treating numerous diseases. Therefore, our study aims to elucidate the underlying mechanism of CTX-induced POF and to explore the therapeutic effect of human urine stem cells (hUSCs) in POF. Methods: CTX-induced POF or ovarian granulosa cell (GCs) apoptosis were treated with hUSCs and their exosomes in vitro and in vivo. Morphological, histological, and functional alternations were examined using multiple approaches. The effector molecules of hUSC-derived exosomes (hUSC-Exo) were determined by differential expression analysis in the ovaries. The target genes of miRNA were accessed by transcriptome sequencing in GCs, and the underlying mechanisms were further elucidated. Results: hUSCs remarkably inhibited CTX-induced apoptosis and promoted the proliferation of GCs, respectively. In addition, we observed that miR-27b-3p was highly expressed in hUSC-Exo and markedly suppressed CTX-induced GC apoptosis by specifically inhibiting the expression of SLC1A4, a serine transporter, in ovarian GCs, which, in turn, elevated the concentration of the intracellular serine by inhibiting the outflux of cellular serine. More importantly, the knockdown of SLC1A4 or simple supplementation of serine suppressed CTX-induced apoptosis of GCs. Finally, we demonstrated that CTX-induced apoptosis of ovarian GCs was essential for POF by reducing the intracellular serine concentration via elevating the expression of SLC1A4, whereas hUSCs protected against CTX-induced POF via miR-27b-3p/SLC1A4/serine axis-mediated activation of the PI3K/AKT/mTOR signaling pathway. Conclusions: Our study suggests that hUSC-based cell therapy or simple supplementation of serine may provide an efficient therapeutic approach for the prevention and treatment of CTX-induced POF clinically. [ABSTRACT FROM AUTHOR]

Examining household carbon emissions through a supply chain perspective reveals the climate impact of consumption behaviors and variations across societal structures and features. Despite the evident and expanding environmental inequality, strategies for its mitigation and prioritization remain debated. This study investigates the origins of carbon emission inequalities from household consumption, using Japan as a case study, a society characterized by aging demographics and comparatively equal income redistribution. By quantitatively analyzing household carbon footprints, we observe a U-shaped distribution in emissions as income levels increase. Notably, the carbon footprint sizes are strikingly similar between the lowest and highest income groups, yet inequalities emerge in education and investments in future generations. Integrating these findings, this study further conducts a scenario analysis to project shifts in future low-carbon lifestyles, indicating that middle-income groups are more prone to achieving personal-level decarbonization. This projection is vital in understanding how to effectively address carbon footprint inequalities, especially considering the entrenched preferences in wealthier demographics for investing in future generations.

Backgroud and aim: Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem, which associated with systemic health problems and causes a higher risk of all-cause mortality. The leading causes of death in NAFLD patients are cardiac complications followed by NAFLD-related liver complications. This study aimed to quantitatively measure the contents of liver and cardiac fat with varying degrees of NAFLD in an obese group and a type 2 diabetes mellitus (T2DM) group to explore differences and correlations. Materials and methods: This study included 170 patients who underwent echo asymmetry and least square estimation-iron quantification sequencing at 3.0 T magnetic resonance imaging. Fat fraction values were quantitatively measured in regions of interest of the liver, myocardium, and periapical adipose tissue. Results: In both the obese and T2DM groups, cardiac fat content was correlated with liver fat content using linear regression (P

Abstract Background Liver fibrosis is an outcome of restoring process in chronic liver injury. Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating liver fibrosis. This study aimed to explore the effect and mechanism of hAMSCs on liver fibrosis. Methods hAMSCs were transplanted into carbon tetrachloride (CCl4)-induced liver fibrosis mice via tail vein, and the effects of hAMSCs on hepatic fibrosis were assessed. The effects of hAMSCs and hAMSCs conditional medium (CM) on the activation of hepatic stellate cells (HSCs) were investigated in vivo and in vitro. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may inhibit the activation of HSCs. Finally, the underlying mechanisms were explored by assessing IGF-1R/PI3K/AKT and GSK3β/β-catenin signaling pathways in the activated HSCs (LX-2) with hAMSCs and hAMSCs transfected with corresponding siRNAs. Results Our results showed that hAMSCs possessed the characterizations of mesenchymal stem cells. hAMSCs significantly reduced liver fibrosis and improved liver function in mice by inhibiting HSCs activation in vivo. Both hAMSCs and hAMSC-CM remarkably inhibited the collagen deposition and activation of LX-2 cells in vitro. Antibody array assay showed that insulin-like growth factor binding protein-3 (IGFBP-3), Dickkopf-3 (DKK-3), and Dickkopf-1 (DKK-1) were highly expressed in the co-culture group and hAMSC-CM group compared with LX-2 group. Western blot assay demonstrated that IGFBP-3, DKK-3, and DKK-1 derived from hAMSCs inhibit LX-2 cell activation through blocking canonical Wnt signaling pathway. Conclusions Our results demonstrated that IGFBP-3, Dkk3, and DKK-1 secreted by hAMSCs attenuated liver fibrosis in mice through inhibiting HSCs activation via depression of Wnt/β-catenin signaling pathway, suggesting that hAMSCs or hAMSC-CM provides an alternative therapeutic approach for the treatment of liver fibrosis.

Aimming at the problems such as low material removal rate and abrasive agglomeration when polishing single crystal silicon carbide wafers with traditional methods, this study proposed a ultrasonic vibration assisted lapping method. It studied the influence of different process parameters including speeds, abrasive concentrations, pressures and abrasive grain sizes on the lapping efficiency and lapping quality of single crystal silicon carbide wafers. The experimental results and theoretical analysis show that ultrasonic vibration effectively improves the material removal rate of single crystal silicon carbide wafer polishing. When the lapping disc speed is 50 r/min, the lapping fluid concentration is 2.5%, the pressure is 0.015 MPa and the abrasive grain size is 0.5 μm, the effect of improving the material removal rate is the most obvious, thus increased by 23.4%, 33.8%, 72.3% and 184.2% respectively. At the same time, by tracking and testing the surface roughness during the lapping process, the best time for ultrasonic vibration-assisted grinding of abrasives with different particle sizes was determined.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical translation. This discrepancy may be due to many variables, such as cell source, timing of implantation, route of administration, and relevant efficacious cell dose, which are critical factors that affect the efficacy of treatment of patients with SCI. Previously, we have evaluated the safety and efficacy of 4 × 106 hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models. To search for a more accurate dose range for clinical translation, we compared the effects of three different doses of hUC-MSCs – low (0.25 × 106 cells/kg), medium (1 × 106 cells/kg) and high (4 × 106 cells/kg) – on subacute SCI repair through an elaborate combination of behavioral analyses, anatomical analyses, magnetic resonance imaging-diffusion tensor imaging (MRI-DTI), biotinylated dextran amine (BDA) tracing, electrophysiology, and quantification of mRNA levels of ion channels and neurotransmitter receptors. Our study demonstrated that the medium dose, but not the low dose, is as efficient as the high dose in producing the desired therapeutic outcomes. Furthermore, partial restoration of the γ-aminobutyric acid type A (GABAA) receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, this study revealed that intrathecal implantation of 1 × 106 hUC-MSCs/kg is an alternative approach for treating subacute SCI.

Abstract Background Targeted therapy combined with immune checkpoint inhibitors is considered a promising treatment for primary advanced hepatocellular carcinoma (HCC). Nevertheless, the difference between synchronous and asynchronous treatment of lenvatinib with programmed death receptor‐1 (PD‐1) inhibitor in advanced HCC is still unclear. The aim of this investigation is to evaluate the effectiveness of synchronous and asynchronous of lenvatinib and PD‐1 inhibitor on the advanced HCC beyond oligometastasis. Methods In this study, 213 patients from four institutions in China were involved. Patients were split into two collections: (1) lenvatinib plus PD‐1 inhibitor were used synchronously (synchronous treatment group); (2) patients in asynchronous treatment group received PD‐1 inhibitor after 3 months of lenvatinib treatment prior to tumour progression. To analyse progression‐free survival (PFS), overall survival (OS), efficacy and safety of patients in both groups, we employed propensity score matching (PSM). Results The 6‐, 12‐ and 24‐month OS rates were 100%, 93.4% and 58.1% in the synchronous treatment group and 100%, 71.5% and 25.3% in the asynchronous treatment group, respectively. In contrast to the asynchronous treatment group, the group treated synchronously exhibited a substantially enhanced OS (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.30–0.66; p < .001). The 6‐, 12‐ and 18‐month PFS rates were 82.6%, 42.6% and 10.8% in the synchronous treatment group and 63.3%, 14.2% and 0% in the asynchronous treatment group, respectively. A significant difference was observed in the PFS rate (HR, 0.46; 95% CI, 0.33–0.63; p < .001) between the two collections. Conclusions Patients with advanced HCC beyond oligometastasis, simultaneous administration of lenvatinib and PD‐1 inhibitor led to significant improvements in survival.

Background: The opioid receptors related to analgesia are mainly μ recipient, the μ receptor has a two-way mode of action: manifested by opioid analgesics and μ1 Receptor binding produces the desired analgesic effect, and μ2 Receptor binding may cause respiratory depression, nausea and vomiting and other adverse reactions. Nalmefene is an opioid receptor antagonist. Low dose Nalmefene has priority over μ2 Receptor binding makes opioid analgesics turn more to μ1 receptor binding, which is reversed μ2 Receptor mediated nausea, vomiting, respiratory depression and other adverse reactions, but does not reverse the analgesic effect. We assume that sufentanil combined with nalmefene could reduce respiratory adverse events in the patients who underwent uvulopalatopharyngoplasty during recovery.Methods: Patients with UPPP under general anesthesia were selected, and divided into control group (group C) and nalmefene group (group N) randomly. Patients in group N received sufentanil 0.1 μg/kg and nalmefene hydrochloride 0.25μg/kg at the end of the operation. Additionally, patients in group C received sufentanil 0.1 μg/kg at the end of the operation. The heart rate (HR) and mean arterial pressure (MAP) were observed and recorded before operation, immediately after extubation, and 5 min after extubation. The breathing recovery time, tracheal extubation time, consciousness score (Ramsay score、sedation-agitation scale (SAS)) and visual analog score (VAS) were carefully recorded at 5 min after extubation, and the various adverse reactions were monitored during the recovery period.Results: Ninety-six patients were finished our study finally. The breathing recovery and extubation time of group N was significantly shorter than those of group C (P

Experiments for simultaneous elimination and detoxification of microgram level of As(Ⅲ) in the presence of micromolar H2O2 and Fe(Ⅱ) which are frequently encountered in natural water were conducted. The results showed that the molar ratio of oxidant to As(III) plays important role in As(III) oxidation under the experimental conditions. The extent of As(Ⅲ) oxidation with single H2O2 or Fe(Ⅱ) ranged from 7.9 % to 60.3 % and 22.2–46.6 %, respectively. Treatments with H2O2/As(Ⅲ) molar ratios in the range 150: 1–750: 1 or Fe(Ⅱ)/As(Ⅲ) molar ratios in the range 37.5: 1–375: 1 were more favor for As(Ⅲ) oxidation respectively, and increasing oxidant concentration did not result in complete As(Ⅲ) oxidation. As(Ⅲ) was completely oxidized and eliminated following the precipitation of ferric hydroxides in 5 reaction minutes when H2O2 and Fe(Ⅱ) coexisted in the reaction system. The interface characterization for the reacted precipitates after the experiment were conducted by using a high-resolution field emission scanning electron microscopy (SEM) coupled with an EX-350 energy dispersive X-ray spectrometer (EDX) and X-ray photoelectron spectroscopy (XPS), respectively. The results showed that As(Ⅴ) was the merely arsenic species and As oxide primary situated in the subsurface layer of the reacted precipitates, whereas Fe was more concentrated in the outermost surface layer. Our research showed that H2O2 and Fe(Ⅱ) at natural level may exert significant influence on arsenic mobilization in natural water. Considering the much more toxic of As(Ⅲ) than that of As(Ⅴ), the research also provide us an environmental friendly choice in the elimination and detoxification of microgram As(Ⅲ) in drinking water.

PurposeOlder patient population with acetabular fractures is increasing rapidly, requiring enhanced recovery. Acute total hip arthroplasty (THA) is a good option for these patients, and it is becoming increasing popular. However, acute THA has different indications in different studies. Therefore, a systematic review is needed to assess and comprehend the indications for acute THA in older patients.MethodsA systematic literature review was conducted to identify a retrospective series or prospective studies in older patients (>60 years) with acetabular fractures. The search timeline was from database construction till December 2021; PubMed, Embase, and Cochrane Library databases were searched. Two trained professional reviewers independently read the full text of documents that met the inclusion criteria and extracted information on the specific methods used and indication information based on the research design.ResultsIn total, there were 601 patients with acetabular fractures aged >60 years from 33 studies were obtained. Twenty-eight studies reported that THA was a feasible treatment option for acetabular fractures in geriatric patients with good outcome. The primary indications were dome impaction, irreducible articular comminution, femoral head injury, and pre-existing osteoarthritis or avascular necrosis. The most common patterns were anterior column and posterior hemitransverse, posterior wall, both columns, and T-type.ConclusionAcute THA is an effective treatment strategy for older patients with acetabular fractures and should be considered when the abovementioned indications are observed on preoperative images. (PROSPERO: CRD42022329555).

PurposeTo assess abdominal fat deposition and lumbar vertebra with iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) and investigate their correlation with menopausal status.Materials and MethodsTwo hundred forty women who underwent routine abdominal MRI and IDEAL-IQ between January 2016 and April 2021 were divided into two cohorts (first cohort: 120 pre- or postmenopausal women with severe fatty livers or without fatty livers; second cohort: 120 pre- or postmenopausal women who were obese or normal weight). The fat fraction (FF) values of the liver (FFliver) and lumbar vertebra (FFlumbar) in the first group and the FF values of subcutaneous adipose tissue (SAT) (FFSAT) and FFlumbar in the second group were measured and compared using IDEAL-IQ.ResultsTwo hundred forty women were evaluated. FFlumbar was significantly higher in both pre- and postmenopausal women with severe fatty liver than in patients without fatty livers (premenopausal women: p < 0.001, postmenopausal women: p < 0.001). No significant difference in the FFlumbar was observed between obese patients and normal-weight patients among pre- and postmenopausal women (premenopausal women: p = 0.113, postmenopausal women: p = 0.092). Significantly greater lumbar fat deposition was observed in postmenopausal women than in premenopausal women with or without fatty liver and obesity (p < 0.001 for each group). A high correlation was detected between FFliver and FFlumbar in women with severe fatty liver (premenopausal women: r=0.76, p

Abstract Introduction Poor sleep quality has been suggested as a risk factor of frailty. However, previous studies that evaluated the association between insomnia and frailty in older population showed inconsistent results. We performed a meta‐analysis to comprehensively evaluate the association. Methods Observational studies related to the aim of the meta‐analysis were identified by search of PubMed, Embase, and Web of Science databases. A random‐effect model incorporating the potential between‐study heterogeneity was used to pool the results. Results Twelve studies including 16,895 old people contributed to the meta‐analysis. Pooled results suggested a significant association between insomnia and frailty in the older population (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.52–2.41, p < .001; I2 = 80%). Subgroup analyses showed consistent association between different symptoms of insomnia and frailty, including difficulty in falling asleep (OR: 1.45), difficulty in maintaining sleep (OR: 1.23), early morning awakening (OR: 1.21), and non‐restorative sleep (OR: 1.84, p for subgroup difference = .15). Results were also consistent for subgroup analyses according to the study country, sample size, cutoffs of age for defining the older population, proportions of men, diagnostic criteria for frailty, adjustment of depression, and scores of study quality (p for subgroup difference all > .05). However, a stronger association was observed for insomnia detected with the Athens Insomnia Scale (OR: 2.92) than that with Pittsburgh Sleep Quality Index (OR: 1.30) or self‐reporting (OR: 1.60, p for subgroup difference = .002). Conclusion Insomnia is independently associated with frailty in the older population.

Three-dimensional printing has great advantages in manufacturing parts with complex internal structures. At present, there are still significant challenges in the unsupported 3D printing of thick-walled parts with inner runners. In this paper, a partitioning method for support-free-fabricating workparts with a built-in inner runner structure is proposed and discussed in detail. With the method, partitioning planes are firstly created according to the direction changes of the inner runner, a “top to bottom” method is used for avoiding the interference of the generated planes, and thirdly the outer surface of the workpiece is considered for a second partition for the support-free purpose. A key algorithm for calculating partitioning planes for inner runner structures is also proposed and introduced in detail, including the iteration method, the calculation for intersectional profile mass centers, and the discussion of the convergence. Algorithm analysis is also performed with a simple model for assessing the influence from the defined parameters, including the proximity Φs and the increment coefficient σ, on the iteration results as well as on the iteration process. Also, an application test is carried out on a column model with a complex inner runner structure built-in. The result from all the tests indicates that the proposed algorithm is successful in partitioning inner runner structures for support-free fabrication.

PurposeTo develop and validate a radiomics nomogram based on ultrasound (US) to predict central cervical lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC).MethodsPTC patients with pathologically confirmed presence or absence of central cervical LN metastasis in our hospital between March 2021 and November 2021 were enrolled as the training cohort. Radiomics features were extracted from the preoperative US images, and a radiomics signature was constructed. Univariate and multivariate logistic regression analyses were used to screen out the independent risk factors, and a radiomics nomogram was established. The performance of the model was verified in the independent test cohort of PTC patients who underwent thyroidectomy and cervical LN dissection in our hospital from December 2021 to March 2022.ResultsIn the independent test cohort, the radiomics model based on long-axis cross-section and short-axis cross-section images outperformed the radiomics models based on either one of these sections (the area under the curve (AUC), 0.69 vs. 0.62 and 0.66). The radiomics signature consisted of 4 selected features. The US radiomics nomogram included the radiomics signature, age, gender, BRAF V600E mutation status, and extrathyroidal extension (ETE) status. In the independent test cohort, the AUC of the receiver operating curve(ROC) of this nomogram was 0.76, outperformingthe clinical model and the radiomics model (0.63 and 0.69, respectively), and also much better than preoperative US examination (AUC, 0.60). Decision curve analysis indicated that the radiomics nomogram was clinically useful.ConclusionsThis study presents an efficient and useful US radiomics nomogram that can provide comprehensive information to assist clinicians in the individualized preoperative prediction of central cervical LN metastasis in PTC patients.

Advanced volumetric imaging methods and genetically encoded activity indicators have permitted a comprehensive characterization of whole brain activity at single neuron resolution in Caenorhabditis elegans. The constant motion and deformation of the nematode nervous system, however, impose a great challenge for consistent identification of densely packed neurons in a behaving animal. Here, we propose a cascade solution for long-term and rapid recognition of head ganglion neurons in a freely moving C. elegans. First, potential neuronal regions from a stack of fluorescence images are detected by a deep learning algorithm. Second, 2-dimensional neuronal regions are fused into 3-dimensional neuron entities. Third, by exploiting the neuronal density distribution surrounding a neuron and relative positional information between neurons, a multi-class artificial neural network transforms engineered neuronal feature vectors into digital neuronal identities. With a small number of training samples, our bottom-up approach is able to process each volume-1024 × 1024 × 18 in voxels-in less than 1 second and achieves an accuracy of 91% in neuronal detection and above 80% in neuronal tracking over a long video recording. Our work represents a step towards rapid and fully automated algorithms for decoding whole brain activity underlying naturalistic behaviors.

The dental pulp plays a crucial role in the long-term maintenance of tooth function. The progress of endodontic treatment and pulp tissue regeneration engineering has made pulp-regeneration therapy promising in clinical practice. However, the mechanisms of pulp regeneration and the role of dental stem cells in development and regeneration have not been fully elucidated. Bridging the gaps between clinical operation and basic research is urgently needed. With the application of single-cell sequencing technology in dental research, the landscapes of human dental pulp cells have begun being outlined. However, the specific cellular heterogeneity of dental pulp cells, especially that of dental stem cells, at different spatial and temporal levels, is still unclear. In this study, we used single-cell RNA sequencing analysis of pulp samples at four different developmental stages and combined the findings with immunohistochemical staining to explore the development of dental pulp and stem cells. The results revealed temporal changes in the proportion of pulp cells during development. For example, mononuclear phagocytes accounted for a higher proportion in early samples. Odontoblasts identified by DMP1 had a higher expression of ion channel-related and neurodevelopment-related genes. Subpopulations were identified in fibroblasts, odontoblasts, and mesenchymal stem cells. We identified a subclass of odontoblasts that expresses DGKI and RRBP1 present in early developmental samples. A population of earlier mesenchymal stem cells expressed the SEPTIN gene, which may have greater proliferative and differentiation potential. Furthermore, dental pulp stem cells can differentiate into two directions: mineralization and myogenesis. In summary, the specific cellular heterogeneity of dental pulp cells was revealed at different spatial and temporal levels. These findings may shed light on the mechanism of tooth development. The gene expression profile of developing pulp cells may help to select cells for regenerative engineering and improve the success of dental pulp regeneration.

Abstract Background Osteosarcoma was the most common primary bone malignancy in children and adolescents. It was imperative to identify effective prognostic biomarkers for this cancer. This study was aimed to identify potential crucial genes of osteosarcoma by integrated bioinformatics analysis. Methods Identification of differentially expressed genes from public data gene expression profiles (GSE42352), functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction and module analysis, Cox regression and survival analysis was conducted. Results Totally 17 co-differential genes were found to be differentially expressed. These genes were enriched in biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway of inflammatory immune response. PPI network was constructed with 63 differentially expressed genes that co-existed between the test set and the validation set. The area under the receiver operating characteristic curve (AUC value) was 0.855, which indicated that the expression of PODN had a good diagnostic value for osteosarcoma. Furthermore, Cox regression and survival analysis revealed 5 genes were statistically significant. Conclusions PODN was regarded as a potential biomarker for the diagnosis and prognosis of osteosarcoma, ACTA2, COL6A1, FAP, OLFML2B and COL6A3, can be used as potential prognostic indicators for osteosarcoma.

Introduction Endothelial cells play an important role in systemic vascular homeostasis, and are the main target of circulating cells and humoral mediators under injury (Tousoulis et al. 2008). Therefore, they [...], Inflammation-induced activation and dysfunction of endothelial cells play an important role in the pathology of multiple vascular diseases. Nicaraven, a potent hydroxyl radical scavenger, has recently been found to have anti-inflammatory roles; however, the mechanism of its action is not fully understood. Here we investigated the effects of Nicaraven on tumor necrosis factor [alpha] (TNF[alpha])-induced inflammatory response in human umbilical vein endothelial cells and we explore the underlying mechanisms related to the nuclear factor-[kappa]B (NF-[kappa]B) signaling pathway. Our results showed that Nicaraven significantly reduced the reactive oxygen species production after TNF[alpha] stimulation. Nicaraven suppressed TNF[alpha]-induced mRNA expression of multiple adhesion molecules and proinflammatory cytokines, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, MCP-1, TNF[alpha], interleulon-1[beta] (IL-1[beta]), IL-6, and IL-8. In addition, Nicaraven inhibited monocyte adhesion and reduced the protein levels of VCAM-1 and ICAM-1. Mechanistically, Nicaraven prevented TNF[alpha]-induced activation of NF-[kappa]B signaling pathway by suppressing the phosphorylation of NF-[kappa]B p65, I[kappa]B[alpha], and I[kappa]B kinase (IKK)[alpha]/[beta], stabilizing I[kappa]B[alpha], and inhibiting the translocation of p65 from cytosol to nucleus. Finally, we showed that Nicaraven improved the functions of endothelial cells, seen as the upregulation of endothelial nitric oxide synthase and increased nitric oxide levels. Our findings indicated that Nicaraven effectively inhibits TNF[alpha] -induced endothelial activation and inflammatory response at least partly through inhibiting NF-[kappa]B signaling pathway. Key words: endothelial cells, Nicaraven, inflammation, TNF[alpha], nuclear factor-[kappa]B. L&apos;activation et le dysfonctionnement des cellules endotheliales engendres par l&apos;inflammation jouent un role important dans la pathologie de multiples maladies vasculaires. On a recemment observe que le nicaravene, un puissant piegeur des radicaux hydroxyl, joue des roles anti-inflammatoires. Toutefois, on ne comprend pas entierement son mode d&apos;action. Nous avons etudie ici les effets du nicaravene sur les reactions inflammatoires provoquees par le TNF[alpha] dans des cellules endotheliales de veine ombilicale humaine et explore les modes d&apos;action sous-jacents lies a la voie de signalisation du facteur NF-[kappa]B. Nos resultats ont montre que le nicaravene permet de faire diminuer de facon marquee la production de derives reactifs de l&apos;oxygene apres une stimulation par le TNF[alpha]. Le nicaravene permettait d&apos;inhiber completement l&apos;expression en ARNm de multiples molecules d&apos;adherence et cytokines proinflammatoires engendree par le TNF[alpha], y compris VCAM-1, ICAM-1, l&apos;E-selectine, MCP-1, TNF[alpha], IL-1[beta], IL-6 et IL-8. De plus, le nicaravene permettait d&apos;inhiber l&apos;adherence des monocytes et de faire diminuer les taux en proteines de VCAM-1 et de ICAM-1. Du point de vue des mecanismes, le nicaravene permettait de prevenir l&apos;activation de la voie de signalisation du facteur NF-[kappa]B engendree par le TNF[alpha] par l&apos;intermediaire de l&apos;inhibition complete de la phosphorylation de NF-[kappa]B p65, d&apos;I[kappa]B[alpha] et d&apos;IKK[alpha]/[beta], de la stabilisation de l&apos;I[kappa]B[alpha] et de l&apos;inhibition de la translocation de p65 du cytosol vers le noyau. Enfin, nous avons montre que le nicaravene permet d&apos;ameliorer le fonctionnement des cellules endotheliales, amelioration observee par la regulation a la hausse de l&apos;oxyde nitrique synthase endotheliale ainsi que par l&apos;augmentation des taux d&apos;oxyde nitrique. Nos resultats montraient que le nicaravene permet d&apos;inhiber efficacement l&apos;activation et la reaction inflammatoire de l&apos;endothelium provoquees par le TNF[alpha], au moins en partie par l&apos;intermediaire de l&apos;inhibition de la voie de signalisation du facteur NF-[kappa]B. [Traduit par la Redaction] Mots-cles: cellules endotheliales, nicaravene, inflammation, TNF[alpha], NF-[kappa]B.

In children with obesity, insulin hypersecretion is proposed to precede insulin resistance. We investigated if metformin could be used to attenuate insulin secretion from palmitate-treated isolated islets and its implication for children with obesity. Human islets were exposed to palmitate for 0.5 or 1 day, when metformin was introduced. After culture, glucose-stimulated insulin secretion (GSIS) was measured. Children with obesity, who had received metformin for over six months (n = 21, age 13.9 ± 1.8), were retrospectively evaluated. Children were classified as either “reducing” or “increasing” based on the difference between AUC0–120 of insulin during OGTT before and after metformin treatment. In human islets, GSIS increased after culture in palmitate for up to 1 day but declined with continued palmitate exposure. Whereas adding metformin after 1 day of palmitate exposure increased GSIS, adding metformin after 0.5 days reduced GSIS. In children with “reducing” insulin AUC0–120 (n = 9), 2 h glucose and triglycerides decreased after metformin treatment, which was not observed in patients with “increasing” insulin AUC0–120 (n = 12). In isolated islets, metformin attenuated insulin hypersecretion if introduced when islet secretory capacity was maintained. In children with obesity, improved glycemic and lipid levels were accompanied by reduced insulin levels during OGTT after metformin treatment.

Animal behavior is organized into nested temporal patterns that span multiple timescales. This behavior hierarchy is believed to arise from a hierarchical neural architecture: Neurons near the top of the hierarchy are involved in planning, selecting, initiating, and maintaining motor programs, whereas those near the bottom of the hierarchy act in concert to produce fine spatiotemporal motor activity. In Caenorhabditis elegans, behavior on a long timescale emerges from ordered and flexible transitions between different behavioral states, such as forward, reversal, and turn. On a short timescale, different parts of the animal body coordinate fast rhythmic bending sequences to produce directional movements. Here, we show that Sublateral Anterior A (SAA), a class of interneurons that enable cross-communication between dorsal and ventral head motor neurons, play a dual role in shaping behavioral dynamics on different timescales. On a short timescale, SAA regulate and stabilize rhythmic bending activity during forward movements. On a long timescale, the same neurons suppress spontaneous reversals and facilitate reversal termination by inhibiting Ring Interneuron M (RIM), an integrating neuron that helps maintain a behavioral state. These results suggest that feedback from a lower-level cell assembly to a higher-level command center is essential for bridging behavioral dynamics at different levels. [ABSTRACT FROM AUTHOR]

Following the current rapid development of the Internet of Things (IoT) and wireless condition monitoring systems, energy harvesters which use ambient energy have become a key part of achieving an energy-autonomous system. Miniature wind energy harvesters have attracted widespread attention because of their great potential of power density as well as the rich availability of wind energy in many possible areas of application. This article provides readers with a glimpse into the state-of-the-art of miniature wind energy harvesters. The crucial factors for them to achieve high working efficiency under lower operational wind speed excitation are analyzed. Various potential energy coupling mechanisms are discussed in detail. Design approaches for broadening operational wind-speed-range given a variety of energy coupling mechanisms are also presented, as observed in the literature. Performance enhancement mechanisms including hydrodynamic configuration optimization, and non-linear vibration pick-up structure are reviewed. Conclusions are drawn and the outlook for each coupling mechanisms is presented.

The activated spindle assembly checkpoint (SAC) potently inhibits the anaphase-promoting complex/cyclosome (APC/C) to ensure accurate chromosome segregation at anaphase. Early studies have recognized that the SAC should be silenced within minutes to enable rapid APC/C activation and synchronous segregation of chromosomes once all kinetochores are properly attached, but the underlying silencers are still being elucidated. Here, we report that the timely silencing of SAC in fission yeast requires dnt1+, which causes severe thiabendazole (TBZ) sensitivity and increased rate of lagging chromosomes when deleted. The absence of Dnt1 results in prolonged inhibitory binding of mitotic checkpoint complex (MCC) to APC/C and attenuated protein levels of Slp1Cdc20, consequently slows the degradation of cyclin B and securin, and eventually delays anaphase entry in cells released from SAC activation. Interestingly, Dnt1 physically associates with APC/C upon SAC activation. We propose that this association may fend off excessive and prolonged MCC binding to APC/C and help to maintain Slp1Cdc20 stability. This may allow a subset of APC/C to retain activity, which ensures rapid anaphase onset and mitotic exit once SAC is inactivated. Therefore, our study uncovered a new player in dictating the timing and efficacy of APC/C activation, which is actively required for maintaining cell viability upon recovery from the inhibition of APC/C by spindle checkpoint.

Abstract Circular RNAs (circRNAs) play vital roles in the pathogenesis and development of multiple cancers, including hepatocellular carcinoma (HCC). Nevertheless, the regulatory mechanisms of circ‐SPECC1 in HCC remain poorly understood. In our study, we found that circ‐SPECC1 was apparently downregulated in H2O2‐treated HCC cells. Additionally, knockdown of circ‐SPECC1 inhibited cell proliferation and promoted cell apoptosis of HCC cells under H2O2 treatment. Moreover, circ‐SPECC1 inhibited miR‐33a expression by direct interaction, and miR‐33a inhibitor partially reversed the effect of circ‐SPECC1 knockdown on proliferation and apoptosis of H2O2‐treated HCC cells. Furthermore, TGFβ2 was demonstrated to be a target gene of miR‐33a and TGFβ2 overexpression rescued the phenotypes of HCC cells attenuated by miR‐33a mimics. Meanwhile, autophagy inhibition by 3‐methyladenine (3‐MA) abrogated the effect of miR‐33a mimics on proliferation and apoptosis of H2O2‐treated HCC cells. Finally, knockdown of circ‐SPECC1 hindered tumor growth in vivo. In conclusion, our study demonstrated that circ‐SPECC1 regulated TGFβ2 and autophagy to promote HCC tumorigenesis under oxidative stress via miR‐33a. These findings might provide potential treatment strategies for patients with HCC.

Abstract Background Colonic transendoscopic enteral tubing (TET) refers to colonic transendoscopic tube-delivered enteral therapy. Colonic TET has been successfully used for frequent colonic administration of drugs or multiple fecal microbiota transplantations (FMTs). This prospective observational study aimed to evaluate possible factors affecting methodology, feasibility and safety of colonic TET. Methods Patients who underwent colonic TET at our center from October 2014 to November 2018 were included. The feasibility, efficacy, and safety of TET were evaluated. Results In total, 224 patients were analyzed. The success rate of TET was 100%. The median retention time of TET tube within the colonic lumen was 8.5 (IQR 7–11) days in 158 patients with tube falling out spontaneously, and the maximum retention time was up to 28 days. These patients were divided into the short-retention group (≤ 8.5 days) and the long-retention group (> 8.5 days). Univariate and multivariate analysis demonstrated that the type of endoscopic clip (p = 0.001) was an independent factor for the retention time. The larger clips as well as a greater number of clips significantly affected the retention time (p = 0.013). No severe adverse event was observed during and after TET. Conclusions Colonic TET is a feasible, practical, and safe colon-targeted drug delivery technique with a high degree of patients’ satisfaction. Two to four large endoscopic clips are recommended to maintain stability of the TET tube within the colon for over 7 days.

ObjectiveTo investigate the efficacies of three cycle regimens in women receiving frozen embryo transfer with a history of cesarean section: natural cycle treatment, hormone replacement therapy and treatment with gonadotropin-releasing hormone agonist.DesignRetrospective cohort study.Methodspatients (N = 6,159) with a history of caesarean section who fulfilled the inclusion criteria were enrolled in the study from January 2014 to December 2019 at the CITIC-Xiangya Hospital of Reproduction and Genetics. Reproductive outcomes of patients in the natural cycle (n = 4,306) versus hormone replacement therapy (n = 1,007) versus gonadotropin-releasing hormone agonist + hormone replacement therapy groups (n = 846) were compared. Continuous data were analyzed using Student’s t-test, and categorical variables were analyzed using the χ2 test. Multivariable logistic regression was used to evaluate the possible relationships between the types of endometrial preparation and pregnancy outcomes after adjusting for confounding factors.ResultsThe unadjusted odds of the miscarriage rate of singleton pregnancies were significantly higher in the hormone replacement therapy compared with the natural cycle (25.5% versus 20.4%, respectively). After adjusting for possible confounding factors, the early miscarriage rate and the miscarriage rate of singleton pregnancies remained significantly higher in the hormone replacement therapy than the natural cycle. The clinical pregnancy rates in the natural cycle, hormone replacement therapy and gonadotropin- releasing hormone agonist + hormone replacement therapy of women with a history of cesarean section was 48.8%, 48% and 47.1%, respectively, and the live birth rates were 37%, 34.1% and 35.7%, respectively.ConclusionsIn women undergoing frozen embryo transfer with a history of cesarean section, hormone replacement therapy for endometrial preparation was associated with a higher early miscarriage rate, albeit after statistical adjustment for confounding factors. However, the risk observed was little and did not influence the overall reproductive performances.