Umbilical cord MSC-derived exosomes improve alveolar macrophage function and reduce LPS-induced acute lung injury.

Acute lung injury (ALI) is a severe condition that can progress to acute respiratory distress syndrome (ARDS), with a high mortality rate. Currently, no specific and compelling drug treatment plan exists. Mesenchymal stem cells (MSCs) have shown promising results in preclinical and clinical studies as a potential treatment for ALI and other lung-related conditions due to their immunomodulatory properties and ability to regenerate various cell types. The present study focuses on analyzing the role of umbilical cord MSC (UC-MSC))-derived exosomes in reducing lipopolysaccharide-induced ALI and investigating the mechanism involved. The study demonstrates that UC-MSC-derived exosomes effectively improved the metabolic function of alveolar macrophages and promoted their shift to an anti-inflammatory phenotype, leading to a reduction in ALI. The findings also suggest that creating three-dimensional microspheres from the MSCs first can enhance the effectiveness of the exosomes. Further research is needed to fully understand the mechanism of action and optimize the therapeutic potential of MSCs and their secretome in ALI and other lung-related conditions.

The novel miR-873-5p-YWHAE-PI3K/AKT axis is involved in non-small cell lung cancer progression and chemoresistance by mediating autophagy.

Non-small cell lung cancer (NSCLC) encompasses approximately 85% of all lung cancer cases and is the foremost cancer type worldwide; it is prevalent in both sexes and known for its high fatality rate. Expanding scientific inquiry underscores the indispensability of microRNAs in NSCLC. Here, we probed the impact of miR-873-5p on NSCLC development and chemoresistance. qRT‒PCR was used to measure the miR-873-5p level in NSCLC cells with or without chemoresistance. A model of miR-873-5p overexpression was constructed. The proliferation and viability of NSCLC cells were evaluated through CCK8 and colony formation experiments. Cell migration and invasion were monitored via Transwell assays. Western blotting was used to determine the levels of YWHAE, PI3K, AKT, EMT, apoptosis, and autophagy-related proteins. The sensitivity of NSCLC cells to the chemotherapeutic agent gefitinib was assessed. Additionally, the correlation of YWHAE with miR-873-5p was validated via a dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Overexpressed miR-873-5p suppressed migration, proliferation, invasion, and EMT while concurrently stimulating apoptotic processes. miR-873-5p was downregulated in NSCLC cells resistant to gefitinib. Upregulating miR-873-5p reversed gefitinib resistance by inducing autophagy. YWHAE was confirmed to be a downstream target of miR-873-5p. YWHAE overexpression promoted the malignant behaviors of NSCLC cells and boosted tumor growth, while these effects were reversed following miR-873-5p overexpression. Subsequent investigations revealed that overexpressing YWHAE promoted PI3K/AKT pathway activation, with miR-873-5p displaying inhibitory effects on the YWHAE-mediated PI3K/AKT signaling cascade. miR-873-5p affects proliferation, invasion, migration, EMT, autophagy, and chemoresistance in NSCLC by controlling the YWHAE/PI3K/AKT axis.

Detection of >400 Cluster of Differentiation Biomarkers and Pathway Proteins in Single Immune Cells by Cyclic Multiplex In Situ Tagging for Single-Cell Proteomic Studies.

The identification and characterization of immune cell subpopulations are critical to reveal cell development throughout life and immune responses to environmental factors. Next-generation sequencing technologies have dramatically advanced single-cell genomics and transcriptomics for immune cell classification. However, gene expression is often not correlated with protein expression, and immunotyping is mostly accepted in protein format. Current single-cell proteomic technologies are either limited in multiplex capacity or not sensitive enough to detect the critical functional proteins. Herein, we present a single-cell cyclic multiplex in situ tagging (CycMIST) technology to simultaneously measure >400 proteins, a scale of >10 times than similar technologies. Such an ultrahigh multiplexity is achieved by reiterative staining of the single cells coupled with a MIST array for detection. This technology has been thoroughly validated through comparison with flow cytometry and fluorescence immunostaining techniques. Both peripheral blood mononuclear cells (PBMCs) and T cells are analyzed by the CycMIST technology, and almost the entire spectrum of cluster of differentiation (CD) surface markers has been measured. The landscape of fluctuation of CD protein expression in single cells has been uncovered by our technology. Further study found T cell activation signatures and protein-protein networks. This study represents the highest multiplexity of single immune cell marker measurement targeting functional proteins. With additional information from intracellular proteins of the same single cells, our technology can potentially facilitate mechanistic studies of immune responses under various disease conditions.

Association between diabetes mellitus and miscarriage, recurrent miscarriage: A meta-study.

BACKGROUND: Previous studies provided inconsistent associations between diabetes mellitus (DM) and miscarriage, recurrent miscarriage (RM). Therefore, this study aims to evaluate the association between DM and miscarriage, specifically RM, through a meta-analysis approach. METHODS: We searched for articles published before July 2023 in PubMed and Web of Science databases. STATA 12.0 software was used to compute all the results collected from included studies. RESULTS: DM was associated with a higher risk of miscarriage, RM (miscarriage: odds ratio [OR]/relative risk [RR] = 1.23, 95% confidence interval [CI] 1.13 to 1.34; RM: OR/RR = 1.73, 95% CI 1.55 to 1.94). T1DM was associated with a higher risk of miscarriage (OR/RR = 1.16, 95% CI 1.07 to 1.26). Similarly, T2DM showed a higher risk of miscarriage (OR/RR = 1.44, 95% CI 1.23 to 1.68). Miscarriage, RM were associated with a higher risk of DM (miscarriage: OR/RR = 1.14, 95% CI 1.08 to 1.19; RM: OR/RR = 1.14, 95% CI 1.08 to 1.20). Furthermore, miscarriage was found to be associated with a higher risk of T2DM (OR/RR = 1.08, 95% CI 1.05 to 1.11). CONCLUSION: In conclusion, our meta-analysis findings indicate a significant association between DM and miscarriages as well as RM. As a result, women with a history of miscarriage should consider regular monitoring of their metabolic health as a potential benefit. Nevertheless, it is important to note that further research is needed to validate the results of our study and shed light on the biological mechanisms underlying these associations.

Comparative analysis of the application with the combination of CMA and karyotype in routine and late amniocentesis.

PURPOSE: This is a retrospective comparative study. We aimed to analyze the results of karyotype and chromosomal microarray analysis (CMA) of amniotic fluid across different gestational weeks and evaluate the clinical value in prenatal diagnosis, particularly in the late pregnancies. METHODS: Samples from 580 pregnant women of 18-23 weeks of gestation (mid-gestation group) and 196 pregnant women of 24-32 weeks of gestation (late group) were performed both standard G-band karyotype analysis and CMA. RESULTS: Among the 580 pregnant women in the routine group, the most common indications were positive Down's screening (213/580, 36.7%), followed by advanced maternal age (196/580, 33.8%); while fetal structural anomalies on ultrasonography were the top reason for amniocentesis in the late group (56/196, 28.6%). In the routine group, the total detection rate was 12.1% (70/580), of which 4.1% (24/580) were identified by karyotype analysis and 11.2% (65/580) by CMA. The total detection rate was 15.3% (30/196) in the late group, of which 5.1% (10/196) were detected by karyotype analysis, and 14.3% (28/196) by CMA. CONCLUSION: Karyotype analysis and CMA are complementary in detecting chromosomal abnormalities. Amniotic cavity puncture in the karyotype analysis in 18-23 weeks of gestation and 24-32 weeks of gestation is safe and effective, more obvious effect on the latter.

In vitro efficacy of Er:YAG laser-activated irrigation versus passive ultrasonic irrigation and sonic-powered irrigation for treating multispecies biofilms in artificial grooves and dentinal tubules: an SEM and CLSM study.

BACKGROUND: Multispecies biofilms located in the anatomical intricacies of the root canal system remain the greatest challenge in root canal disinfection. The efficacy of Er:YAG laser-activated irrigation techniques for treating multispecies biofilms in these hard-to-reach areas has not been proved. The objective of this laboratory study was to evaluate the effectiveness of two Er:YAG laser-activated irrigation techniques, namely, photon-induced photoacoustic streaming (PIPS) and shock wave-enhanced emission photoacoustic streaming (SWEEPS), in treating multispecies biofilms within apical artificial grooves and dentinal tubules, in comparison with conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI), and sonic-powered irrigation (EDDY). Two types of multispecies root canal biofilm models were established in combination with two assessment methods using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) with the aim to obtain more meaningful results. METHODS: Ninety extracted human single-rooted premolars were chosen for two multispecies biofilm models. Each tooth was longitudinally split into two halves. In the first model, a deep narrow groove was created in the apical segment of the canal wall. After cultivating a mixed bacterial biofilm for 4 weeks, the split halves were reassembled and subjected to five irrigation techniques: CNI, PUI, EDD, PIPS, and SWEEPS. The residual biofilms inside and outside the groove in Model 1 were analyzed using SEM. For Model 2, the specimens were split longitudinally once more to evaluate the percentage of killed bacteria in the dentinal tubules across different canal sections (apical, middle, and coronal thirds) using CLSM. One-way analysis of variance and post hoc multiple comparisons were used to assess the antibiofilm efficacy of the 5 irrigation techniques. RESULTS: Robust biofilm growth was observed in all negative controls after 4 weeks. In Model 1, within each group, significantly fewer bacteria remained outside the groove than inside the groove (P < 0.05). SWEEPS, PIPS and EDDY had significantly greater biofilm removal efficacy than CNI and PUI, both from the outside and inside the groove (P < 0.05). Although SWEEPS was more effective than both PIPS and EDDY at removing biofilms inside the groove (P < 0.05), there were no significant differences among these methods outside the groove (P > 0.05). In Model 2, SWEEPS and EDDY exhibited superior bacterial killing efficacy within the dentinal tubules, followed by PIPS, PUI, and CNI (P < 0.05). CONCLUSION: Er:YAG laser-activated irrigation techniques, along with EDDY, demonstrated significant antibiofilm efficacy in apical artificial grooves and dentinal tubules, areas that are typically challenging to access.

Rapid, High-Throughput Single-Cell Multiplex In Situ Tagging (MIST) Analysis of Immunological Disease with Machine Learning.

The cascade of immune responses involves activation of diverse immune cells and release of a large amount of cytokines, which leads to either normal, balanced inflammation or hyperinflammatory responses and even organ damage by sepsis. Conventional diagnosis of immunological disorders based on multiple cytokines in the blood serum has varied accuracy, and it is difficult to distinguish normal inflammation from sepsis. Herein, we present an approach to detect immunological disorders through rapid, ultrahigh-multiplex analysis of T cells using single-cell multiplex in situ tagging (scMIST) technology. scMIST permits simultaneous detection of 46 markers and cytokines from single cells without the assistance of special instruments. A cecal ligation and puncture sepsis model was built to supply T cells from two groups of mice that survived the surgery or died after 1 day. The scMIST assays have captured the T cell features and the dynamics over the course of recovery. Compared with cytokines in the peripheral blood, T cell markers show different dynamics and cytokine levels. We have applied a random forest machine learning model to single T cells from two groups of mice. Through training, the model has been able to predict the group of mice through T cell classification and majority rule with 94% accuracy. Our approach pioneers the direction of single-cell omics and could be widely applicable to human diseases.

Multimodal and Multicolor Anti-counterfeiting Realized in CaCd2Ga2Ge3O12 with a Single Activator of Mn2.

The continuously growing significance of information security and authentication has put forward many new requirements and challenges for modern luminescent materials and anti-counterfeiting technologies. Recently, luminescent materials have attracted much attention in this field owing to their legibility, repeatability, multicolor, and multiple stimuli-responsive nature. In this work, the efficient multicolor and multimodal luminescence material CaCd2Ga2Ge3O12:Mn2+ was successfully designed and synthesized using the strategy of single-doped Mn2+ in a single matrix. Also, we combined the morphology, crystal structure, energy band calculation, luminescence properties, and trap analysis to study the optical data storage capacity of CaCd2Ga2Ge3O12:Mn2+. Interestingly, in the presence of the 254 nm UV lamp, the sample can exhibit a tunable emission color from bule to cyan to yellow by increasing the dopant concentration of Mn2+. Also, under the afterglow and thermoluminescence luminescence modes, it presented strong yellow emission centered at 558 nm. Based on the advantage of multiple tunable luminescence, samples were made into anti-counterfeiting ink and were used to print four optical devices through the screen printing technology. The results show that the material has excellent multicolor anti-counterfeiting properties under the three luminescence modes, which has contributed to the development of many kinds of luminescent anti-counterfeiting materials for security purposes.

The effects of brominated flame retardants (BFRs) on pro-atherosclerosis mechanisms.

Brominated flame-retardants (BFRs) are environmental endocrine disruptors, comprising several pollutants, which potentially affect the endocrine system and cause dysfunction and disease. Widespread BFR exposure may cause multisystem toxicity, including cardiovascular toxicity in some individuals. Studies have shown that BFRs not only increase heart rate, induce arrhythmia and cardiac hypertrophy, but also cause glycolipid metabolism disorders, vascular endothelial dysfunction, and inflammatory responses, all of which potentially induce pre-pathological changes in atherosclerosis. Experimental data indicated that BFRs disrupt gene expression or signaling pathways, which cause vascular endothelial dysfunction, lipid metabolism-related disease, inflammation, and possibly atherosclerosis. Considerable evidence now suggests that BFR exposure may be a pro-atherosclerotic risk factor. In this study, we reviewed putative BFR effects underpinning pro-atherosclerosis mechanisms, and focused on vascular endothelial cell dysfunction, abnormal lipid metabolism, pro-inflammatory cytokine production and foam cell formation. Consequently, we proposed a scientific basis for preventing atherosclerosis by BFRs and provided concepts for further research.

In situ surface modification of forward osmosis membrane by polydopamine/polyethyleneimine-silver nanoparticle for anti-fouling improvement in municipal wastewater treatment.

In this work, we demonstrate the surface functionalization of cellulose triacetate membrane with co-deposition of polydopamine (PDA)/polyethyleneimine (PEI) and silver nanoparticles (AgNPs) for antifouling property in municipal wastewater treatment. PDA/PEI was first coated on the membrane surface by single-step co-deposition, while AgNPs were formed in situ through catechol groups of PDA immobilizing silver ions and subsequently reducing. The successful surface modification was verified by different membrane characterization techniques. The modified PDA/PEI-nAg CTA membrane exhibits enhanced hydrophilicity and improved antiadhesion and antimicrobial activity. Furthermore, the functional layer had an indistinctive effect on the membrane transport parameters. In addition, dynamic forward osmosis (FO) fouling experiment with raw municipal wastewater as feed solution indicated that the PDA/PEI-nAg CTA membrane exhibited notably lower water flux decrease compared to the nascent CTA membrane. The results of confocal laser scanning microscopy (CLSM) showed that PDA/PEI-nAg CTA membranes effectively reduced the adsorption of organic foulants (proteins and polysaccharides) and inhibited the formation and development of the fouling layer. The membrane surface modification of the CTA membrane with PDA/PEI and AgNPs efficiently mitigated membrane fouling in municipal wastewater treatment.

Spatial Multiplex In Situ Tagging (MIST) Technology for Rapid, Highly Multiplexed Detection of Protein Distribution on Brain Tissue.

Highly multiplexed analysis of biospecimens significantly advances the understanding of biological basics of diseases, but these techniques are limited by the number of multiplexity and the speed of processing. Here, we present a rapid multiplex method for quantitative detection of protein markers on brain sections with the cellular resolution. This spatial multiplex in situ tagging (MIST) technology is built upon a MIST microarray that contains millions of small microbeads carrying barcoded oligonucleotides. Using antibodies tagged with UV cleavable oligonucleotides, the distribution of protein markers on a tissue slice could be "printed" on the MIST microarray with high fidelity. The performance of this technology in detection sensitivity, resolution, and signal-to-noise level has been fully characterized by detecting brain cell markers. We showcase the codetection of 31 proteins simultaneously within 2 h, which is about 10 times faster than the other immunofluorescence-based approaches of similar multiplexity. A full set of computational toolkits was developed to segment the small regions and identify the regional differences across the entire mouse brain. This technique enables us to rapidly and conveniently detect dozens of biomarkers on a tissue specimen, and it can find broad applications in clinical pathology and disease mechanistic studies.

Serum lipid profile in relation to free thyroxine and the effect of levothyroxine treatment on lipids in patients with isolated hypothyroxinemia during pregnancy: a single-center retrospective study.

BACKGROUND: Thyroid function is widely considered a lipid metabolism regulator. However, studies on lipid metabolism in pregnant women with low free thyroxine (FT4) levels are limited and inconclusive. Furthermore, the association between maternal FT4 deficiency and adverse lipid metabolic parameters is unknown. Therefore, we aimed to investigate this association and the effects of levothyroxine (L-T4) treatment on these metabolic indicators. METHODS: This retrospective study included 164 patients with isolated hypothyroidism (IH) (FT4 levels below the 5th percentile with normal thyroid stimulating hormone levels according to the gestational-specific reference range) and 407 euthyroidism patients (control group who had regular antenatal examinations at Zhejiang Provincial People's Hospital, Hangzhou, China) between January 1, 2019, and December 31, 2020. Patients with IH were divided into levothyroxine (L-treatment group, n = 77) and dietary iodine supplement treatment groups (dietary treatment group, n=87) according to the hospital's treatment policy and clinical experience. The intervention lasted for at least 8 weeks. Metabolic indicators, including thyroid function and lipid parameters, were collected at least twice before and after the intervention. Other data collected included maternal age, history of abortion, prepregnancy BMI, and gestational weight gain (Fig. 1). RESULTS: Compared with the control group, Patients with IH had a higher degree of dyslipidemia, reflected in elevated total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) levels. In IH patients, an inverse correlation was found between FT4 and TG levels, which remained after adjusting for prepregnancy BMI. The L-treatment group demonstrated a significantly slower rate of hypercholesterolemia progression during pregnancy than the dietary treatment group. In addition, there was a relationship between the therapeutic effect and the degree of disease, with the main factors being FT4, TSH and TG levels prior to starting treatment. CONCLUSIONS: Low FT4 levels were associated with elevated blood lipid levels. Serum FT4 and lipid levels in patients could be improved by medical intervention.

The modification of biomass waste by cerium-based MOFs for efficient phosphate removal: excellent performance and reaction mechanism.

Due to the possibility of causing eutrophication, excessive phosphate discharged into water bodies always threatens the stabilization of aquatic ecosystem. A promising strategy is to remove phosphate from water by the utilization of biomass waste as adsorbents. In this paper, the corn straw (CS) and pine sawdust (PS) are chosen for adsorption; however, the phosphate removal capacities of them are very limited. Considering the high phosphate uptake of trivalent cerium, Ce (III)-based nanoparticles (CD and CT) are selected to be loaded on the biomass by hydrothermal synthesis to obtain four modified materials. CD is metal organic frameworks (MOFs) with Ce5(BDC)7.5(DMF)4 as its molecular structure, while CT is MOFs derivatives with [Ce (HCOO)]n as its crystal structure. The adsorption capacities of CS-CD, PS-CD, CS-CT and PS-CT reach 181.38, 183.27, 225.55 and 186.23 mg/g. But on account of the different molecular structures, CS-CD and PS-CD achieve great phosphate uptake under wide applicable scope of pH from 2 to 11, whereas CS-CT and PS-CT only under acidic conditions. The analysis of the adsorption mechanism indicates that due to the unsaturated coordination bond of CD, it could remove phosphate through coprecipitation and ion exchange even under alkaline conditions.

Ultrasensitive photoelectrochemical aptasensor for diclofenac sodium based on surface-modified TiO2-FeVO4 composite.

Herein, a photoelectrochemical (PEC) aptasensing platform was designed by integrating surface oxygen vacancy (OV) defects, Ti3+ self-doping, the heterojunction, and resonance energy transfer (RET) effect into one platform for the detection of diclofenac sodium (DCF). Briefly, OV defects were introduced on TiO2 nanospheres with simultaneous Ti3+ self-doping, followed by a well-separated deposition of FeVO4 nanoparticles on TiO2 to obtain a Ti3+-O-TiO2/FeVO4 heterojunction. The surface modification of OVs, Ti3+ doping, and deposition of FeVO4 were confirmed by SEM, XPS, EPR, DRS, and PEC measurements. The surface OVs and doping of Ti3+ species created a new donor (defect) energy level under the conduction band of TiO2, which minimized the bandgap and thereby improved the visible light absorption of TiO2. Moreover, the capture of photo-excited electrons by surface OVs could hinder the electron-hole recombination. Due to the intimate surface contact and perfect energy matching between TiO2 and FeVO4, the formation of heterojunction decreased the bandgap and facilitated the electron-hole separation of TiO2. All these above events contributed to the enhancement of the PEC signals, which were then quenched by the RET effect between Ti3+-O-TiO2/FeVO4 and Au nanoparticle (AuNP)-labeled cDNA that had been attached to its complementary DCF aptamer on Ti3+-O-TiO2/FeVO4|ITO. The addition of target-DCF detached AuNP-labeled cDNA from the electrode to recover the photocurrent, resulting in a "signal-on" PEC aptasensor that exhibited a 0.1-500-nM linear range and a detection limit of 0.069 nM for DCF, attributed to the excellent amplification of the proposed aptasensing platform.

PM2.5 promoted lipid accumulation in macrophage via inhibiting JAK2/STAT3 signaling pathways and aggravating the inflammatory reaction.

BACKGROUND: Abnormal lipid accumulation in macrophages may lead to macrophages foaming, which is the most important pathological process of atherosclerosis. Atmospheric PM2.5 could enter the blood circulation and further affect the lipid metabolism of macrophages. But the underlying mechanism is not unclear. This study was undertaken to clarify the effect of PM2.5 on lipid metabolism in macrophages, and to explore the role of inflammatory reaction and JAK2/STAT3 signaling pathway in this process. METHOD: Macrophages derived from THP-1 cells were exposed to PM2.5 (0,100,200,400 µg/mL) for 6 h and 12 h. STAT3 agonist ColivelinTFA is used to specifically excite STAT3. The survival rate of macrophages was detected by CCK-8. The lipid levels in macrophages were detected by colorimetry. The levels of inflammatory factors secreted by macrophages were detected by ELISA. Q-PCR was used to detect the mRNA expression levels, and Western Blot was used to detect the protein expression levels of JAK2/STAT3 pathway genes. RESULT: The survival rate of macrophages was reduced by PM2.5, and the levels of TG, T-CHO and LDL-C of macrophages exposed to PM2.5 were increased. PM2.5 led to the increasing level of IL-6 and the decreasing level of IL-4, and the JAK2/STAT3 signaling pathway was inhibited by PM2.5. Colivelin TFA significantly decreased the increasing levels of TG, T-CHO and LDL-C levels, and increased the decreasing mRNA levels of IL-4, and LPL induced by PM2.5 (p < 0.05). DISCUSSION: PM2.5 could cause the lipid accumulation of macrophages by inhibiting the JAK2/STAT3 signaling pathway, and inflammatory responses may be involved in this process.

Effect of Notch pathway on lipid accumulation induced by mono-2-ethylhexyl phthalate on 3T3-L1 cells.

BACKGROUND: Mono-2-ethylhexyl phthalate (MEHP) is a major metabolite of di (2-ethylhexyl) phthalate (DEHP). Our previous researches have shown that MEHP can induce lipid accumulation in preadipocytes, while, the underlying mechanism is unclear. The present study was undertaken to clarify the effect of Notch pathway on lipid accumulation induced by MEHP. METHODS: 3T3-L1 preadipocytes were exposed to MEHP (0, 10, 50, 250 µM and 0.1%DMSO) for the whole differentiation phase. Then the level of TG and cell cycle were detected. RT-PCR was used to detect the mRNA expression and Western blot was used to detect the expression of protein by Notch pathway genes and lipid metabolic related genes. RESULTS: In this study, the level of TG in the 250 µM and 250 µM MEHP groups was significantly higher than that in the control, DMSO and 10 µM MEHP groups (P < 0.05). The relative mRNA level of Notch-1, Notch-3, Notch-4, Jagged-2 and Dll-4 in 250 µM group was higher than other groups (P < 0.05). The expression of Notch signal pathway proteins increased in MEHP treated groups, and the expression of Notch-2, Jagged-1, Jagged-2, Dll-1 and Dll-4 in 250 µM group were significantly higher than control group (P < 0.05). The expression of lipid metabolic related gene mRNA and protein increased in MEHP treated groups, and 250 µM MEHP group was higher than other groups (P < 0.05). The intracellular TG content was significantly correlated with the expression levels of Notch-1 and Jagged-2 mRNA (P < 0.05). CONCLUSION: In this study, we have found that MEHP exposure could increase the TG content in 3T3-L1 cells. The expression of Notch pathway mRNA and proteins were disturbed by the MEHP. Notch-1 and its ligand Jagged-2 play a critical role in the abnormal lipid metabolism in 3T3-L1 cells caused by MEHP.

Treatment Outcomes of Pulpectomy in Primary Maxillary Incisors Filled with ZOE and Metapex: A Two-year Retrospective Study.

OBJECTIVES: To address a literature gap by evaluating, in a larger set of samples, the clinical and radiographic outcomes of pulpectomy in primary maxillary incisors using ZOE and calcium hydroxide/iodoform paste. To also identify the predisposing factors for treatment outcomes. STUDY DESIGN: Medical charts of 124 patients (aged 16 to 60 months) and radiographs of their incisors (309 incisors) were reviewed (128 with ZOE and 181 with Metapex). All incisors were restored with composite resin crowns. RESULTS: The radiographic success rates for ZOE and Metapex were: 85.9% and 82.9% at the 12-month recall, and 69.2% and 64% at the 24-month recall, with no statistically significant difference between the two groups. Clinical failures occurred more frequently in the Metapex group (P = 0.006), as clinical signs of pain and soft tissue pathosis were found in 6.2% of the Metapex cases at 24 months but none in the ZOE group. Significant predisposing factors for radiographic success were type of tooth, degree of obturation at recalls, and preoperative root resorption. CONCLUSIONS: The radiographic success rates are comparable between the ZOE and Metapex groups. Clinical pathological manifestations such as pain and soft tissue pathosis are seen in the Metapex group at recalls, but none in the ZOE group. Predisposing factors such as type of incisor, preoperative root resorption, and extent of filling at recalls are associated with the radiographic success rate.

Deep Profiling of Cellular Heterogeneity by Emerging Single-Cell Proteomic Technologies.

The ability to comprehensively profile cellular heterogeneity in functional proteome is crucial in advancing the understanding of cell behavior, organism development, and disease mechanisms. Conventional bulk measurement by averaging the biological responses across a population often loses the information of cellular variations. Single-cell proteomic technologies are becoming increasingly important to understand and discern cellular heterogeneity. The well-established methods for single-cell protein analysis based on flow cytometry and fluorescence microscopy are limited by the low multiplexing ability owing to the spectra overlap of fluorophores for labeling antibodies. Recent advances in mass spectrometry (MS), microchip, and reiterative staining-based techniques for single-cell proteomics have enabled the evaluation of cellular heterogeneity with high throughput, increased multiplexity, and improved sensitivity. In this review, the principles, developments, advantages, and limitations of these advanced technologies in analysis of single-cell proteins, along with their biological applications to study cellular heterogeneity, are described. At last, the remaining challenges, possible strategies, and future opportunities that will facilitate the improvement and broad applications of single-cell proteomic technologies in cell biology and medical research are discussed.

Fast Affinity Induced Reaction Sensor Based on a Fluorogenic Click Reaction for Quick Detection of Protein Biomarkers.

Despite numerous biosensors currently available, the routine biomarker detection still largely relies on traditional ELISA and Western blot. Those standard techniques are labor intensive and time-consuming. Herein we introduce a fast affinity induced reaction sensor (FAIRS) that overcomes a few limitations of traditional and emerging biosensors. FAIRS is a general, one-step method and is naturally specific in detection. FAIRS probes are composed of a sandwich ELISA antibody pair that is conjugated with two fluorogenic click chemicals. This technology leverages significant differences of antibody affinity and chemical reaction rate, which are characterized to guide probe design. The stability, sensitivity, detection range, and response time are fully characterized. Application to IL-6 detection using blood serum and cell culture medium demonstrates that FAIRS can quantify IL-6 with high sensitivity in one step. With the unique features, FAIRS probes may find broad applications in medical sciences and clinical diagnostics, where quick detection of biomarkers is demanded.

Broad-spectrum next-generation sequencing-based diagnosis of a case of Nager syndrome.

BACKGROUND: Nager syndrome is a rare genetic syndrome characterized by craniofacial and preaxial limb anomalies. Haploinsufficiency of the SF3B4 gene has been identified as a significant reason for Nager syndrome. Treacher Collins syndrome (TCS) has similar facial features; however, the TCOF1, POLR1D, and POLR1C genes have been reported as the critical disease-causing genes. Similar phenotypes make it easy to misdiagnose. CASE REPORT: In this report, we have presented a case of one newborn with acrofacial dysostosis, who was first diagnosed with TCS. Expanded next-generation sequencing eventually detected a (c.1A>G) heterozygous mutation in the SF3B4 gene at chr1:149899651 that was confirmed by Sanger sequencing. Combined with his preaxial limb anomalies discovered after his death, a diagnosis of Nager syndrome was made. CONCLUSIONS: This report presents one patient with Nager syndrome who was initially misdiagnosed with TCS. Correct genetic testing will be beneficial to future prenatal diagnosis.