Erianin inhibits tumor growth by promoting ferroptosis and inhibiting invasion in hepatocellular carcinoma through the JAK2/STAT3/SLC7A11 pathway.

Iron has been found to be involved in the tumor cell proliferation process, which can lead to the increased sensitivity of cancer cells to ferroptosis. Since erianin is associated with oxidative stress in hepatocellular carcinoma (HCC), we hypothesized that the therapeutic effect and mechanism of erianin on HCC is related to ferroptosis. HCC cells were stimulated with increase of erianin concentrations for 24 h, and the survival rates of Huh-7 and HepG2 cells gradually decreased. After intervention with different doses of erianin, cell proliferation, clone number, and invasion were prominently decreased, apoptosis ratio was increased. Moreover, Nec-1, CQ, and Z-VAD had no effect on the cell viability induced by erianin, while the combination of ferroptosis inhibitors (deferoxamine mesylate, ferrostatin-1, and liproxstatin-1) and erianin prominently increased cell survival rate. Erianin pretreatment induced ferroptosis by enhancing reactive oxygen species, MDA, and Fe2+ levels, and reducing GSH levels. Erianin activated JAK2/STAT3 pathway and inhibited SLC7A11 and GPX4 expression, thereby inducing ferroptosis. Besides, tumor growth was significantly inhibited in the erianin-treated mice, and there was no obvious toxicity in the mice. Erianin reduced proliferation and invasion of HCC cells by inducing ferroptosis by blocking the JAK2/STAT3/SLC7A11 pathway, thereby impeding tumor growth.

Downregulation of WNK4 expression facilitates the proliferation of gastric cancer cells via activation of the STAT3 signaling pathway.

WNK lysine deficient protein kinase 4 (WNK4) has been shown to be significantly associated with cancer progression. Nevertheless, its involvement in gastric cancer (GC) is unclear. The objective of this work was to investigate the WNK4's regulatory mechanism in GC. Quantitative RT-PCR and immunoblots revealed that WNK4 expression was downregulated in GC and that low expression of WNK4 was strongly linked to poor prognosis. Functional assays including cell counting kit-8 assay and colony formation assay demonstrated that overexpression of WNK4 led to limited tumor proliferation both in vitro and in vivo, while the WNK4 reduction yielded to the opposite results. Gene Set Enrichment Analysis (GSEA) indicated a potential association between WNK4 and the signal transducer and activator of transcription (STAT3). WNK4 suppressed the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in GC cells. The inhibition of the STAT3 pathway with Stattic reversed growth and proliferation induced by WNK4 knockdown in GC cells. These findings provide new insights for identifying key therapeutic targets for GC in the future.

Initial respiratory support modality and outcome in preterm infants with less than 32 weeks of gestation in China: A multicentre retrospective cohort study.

BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.

Treatment of facial and non-facial lentigines with a 730 nm picosecond titanium: Sapphire laser is safe and effective.

OBJECTIVE: A 730 nm picosecond-domain laser was developed to improve the clearance of pigmented lesion and reduce adverse events. This study assessed the safety and efficacy of this system for the clearance of lentigines and explores how the short picosecond pulses interact with tissue via histology. STUDY DESIGN AND METHODS: Twenty subjects with Fitzpatrick skin types II-IV were enrolled in this prospective, IRB-approved study. Four treatments were administered using a 730 nm picosecond-domain laser. Pre- and posttreatment photos were assessed by blinded reviewers at 4- and 12-week follow-up visits, using a 5-point clearance scale. Subject satisfaction was measured using a 5-point scale. Investigator Global Improvement Score (IGIS) was performed at the 4- and 12-week follow-up visits, using an 11-point clearance scale. Subject pain level was measured using an 11-point scale (no pain [0], extreme pain [10]). Histology of 730 and 532 nm picosecond pulses was compared with 755 and 532 nm nanosecond pulses. RESULTS: Sixteen subjects with a total of 118 discontinuous treatment areas, each comprised of 1-20 lesions, completed all study visits. Thirty body regions were studied, including arms (6), hands (16), scalp (1), forehead (2), face (3), and back (2). Spot sizes ranging from 2 to 5 mm diameters were used with fluences ranging from 0.8 to 4.0 J/cm2 . Mean pain score was 3.6 of 10 for all four treatments. Ninety-nine percent of randomly paired 4-week posttreatment images and 100% of 12-week posttreatment images were correctly identified from their respective baseline images by three blinded reviewers. Mean IGIS demonstrated scores of 6.7 and 7.0 at 4- and 12-week follow-up visits, respectively. At the 4- and 12-week follow-up visits, 76% and 73% of subjects, respectively, were satisfied to highly satisfied. The mean clearance score for all 118 treatment areas was 3 of 4 in follow-up visits. At 12-week follow-up, 36% of 118 treatment areas had a clearance score of 4, and 38% had a clearance score of 3. Post treatment, there was typical erythema, edema, dryness, crusting, and itching but negligible purpura, no pinpoint bleeding, blistering or scarring, and no significant hyperpigmentation or hypopigmentation. Histology showed diffuse, focal epidermal vacuolization ~5-10 µm in diameter and mild extravasation of erythrocytes with 730 nm picosecond pulses, while diffuse epidermal vacuolization was observed with coalescence of vacuoles (~20-100 µm), junctional clefting and mild extravasation of erythrocytes with 755 nm nanosecond pulses. Picosecond pulses of the wavelength of 532 nm produced diffuse, focal epidermal vacuolization and larger dermal vacuoles to depths of 500 µm, while 532 nm nanosecond pulses produced diffuse epidermal vacuolization with coalescence of vacuoles and marked dermal hemorrhage. CONCLUSION: This study demonstrated the potential of a new 730 nm picosecond-domain laser for the clearance of lentigines. The results showed good clearance with no adverse events and good subject satisfaction in patients with skin type II-III. Additional studies need to be conducted on darker skin types. The histopathologic findings demonstrate that the picosecond 730 nm laser produces excellent selectivity for pigment with minimal disruption of the dermal-epidermal junction and may therefore reduce healing times and the risk of adverse events.

A methylation-based mRNA signature predicts survival in patients with gastric cancer.

BACKGROUND: Evidence suggests that altered DNA methylation plays a causative role in the occurrence, progression and prognosis of gastric cancer (GC). Thus, methylated-differentially expressed genes (MDEGs) could potentially serve as biomarkers and therapeutic targets in GC. METHODS: Four genomics profiling datasets were used to identify MDEGs. Gene Ontology enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis were used to explore the biological roles of MDEGs in GC. Univariate Cox and LASSO analysis were used to identify survival-related MDEGs and to construct a MDEGs-based signature. The prognostic performance was evaluated in two independent cohorts. RESULTS: We identified a total of 255 MDEGs, including 192 hypermethylation-low expression and 63 Hypomethylation-high expression genes. The univariate Cox regression analysis showed that 83 MDEGs were associated with overall survival. Further we constructed an eight-MDEGs signature that was independent predictive of prognosis in the training cohort. By applying the eight-MDEGs signature, patients in the training cohort could be categorized into high-risk or low-risk subgroup with significantly different overall survival (HR = 2.62, 95% CI 1.71-4.02, P < 0.0001). The prognostic value of the eight-MDEGs signature was confirmed in another independent GEO cohort (HR = 1.35, 95% CI 1.03-1.78, P = 0.0302) and TCGA-GC cohort (HR = 1.85, 95% CI 1.16-2.94, P = 0.0084). Multivariate cox regression analysis proved the eight-MDEGs signature was an independent prognostic factor for GC. CONCLUSION: We have thus established an innovative eight-MDEGs signature that is predictive of overall survival and could be a potentially useful guide for personalized treatment of GC patients.

Characterization of ginsenoside compound K metabolites in rat urine and feces by ultra-performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

Ginsenoside compound K (CK) is an active metabolite of ginsenoside and has been shown to have ameliorative property in various diseases. However, the detailed in vivo metabolism of this compound has rarely been reported. In the present study, a method using liquid chromatography quadrupole time-of-flight tandem mass spectrometry together with multiple data processing techniques, including extracted ion chromatogram, multiple mass defect filter and MS/MS scanning, was developed to detect and characterize the metabolites of CK in rat urine and feces. After oral administration of CK at a dose of 50 mg/kg, urine and feces were collected for a period of time and subjected to a series of pretreatment. A total of 12 metabolites were tentatively or conclusively identified, comprising 11 phase I metabolites and a phase II metabolite. Metabolic pathways of CK has been proposed, including oxidation, deglycosylation, deglycosylation with sequential oxidation and dehydrogenation and deglycosylation with sequential glucuronidation. Relative quantitative analyses suggested that deglycosylation was the main metabolic pathway. The result could offer insights for better understanding of the mechanism of its pharmacological activities.

Construction of Fully Substituted 2-Pyridone Derivatives via Four-Component Branched Domino Reaction Utilizing Microwave Irradiation.

Microwave irradiation, four-component branched domino reaction of methyl acetoacetate/2,4-pentanedione, diethyl malonate, triethyl orthoformate and amines offering an extremely efficient strategy for the construction of fully substituted 2-pyridone derivatives under sustainable conditions is established. This self-sorting branched domino transformation is proposed to proceed separate through N-nucleophilic addition and imine-enamine tautomerization/condensation reaction generated from enamino ester and diethyl ethoxymethylenemalonate, and then would be subjected to an aza-ene reaction and intramolecular cyclization mechanism to afford the 2-pyridones with only water and ethanol as byproducts. The simple experimental procedure, high bond-forming efficiency, step and atom economy, inexpensive readily available starting materials, moderate to excellent yields, and good functional group compatibility are other noteworthy advantages of this method.

A 3D-Printed, Portable, Optical-Sensing Platform for Smartphones Capable of Detecting the Herbicide 2,4-Dichlorophenoxyacetic Acid.

Onsite rapid detection of herbicides and herbicide residuals in environmental and biological specimens are important for agriculture, environmental concerns, food safety, and health care. The traditional method for herbicide detection requires expensive laboratory equipment and a long turnaround time. In this work, we developed a single-stripe microliter plate smartphone-based colorimetric device for rapid and low-cost in-field tests. This portable smartphone platform is capable of screening eight samples in a single-stripe microplate. The device combined the advantages of small size (50 × 100 × 160 mm3) and low cost ($10). The platform was calibrated by using two different dye solutions, i.e. methyl blue (MB) and rhodamine B, for the red and green channels. The results showed good correlation with results attained from a traditional laboratory reader. We demonstrated the application of this platform for detection of the herbicide 2,4-dichlorophenoxyacetic acid in the range of 1 to 80 ppb. Spiked samples of tap water, rat serum, plasma, and human serum were tested by our device. Recoveries obtained varied from 95.6% to 105.2% for all of the spiked samples using the microplate reader and from 93.7% to 106.9% for all of the samples using the smartphone device. This work validated that the smartphone optical-sensing platform is comparable to the commercial microplate reader; it is eligible for onsite, rapid, and low-cost detection of herbicides for environmental evaluation and biological monitoring.

High-Throughput Optical Sensing Immunoassays on Smartphone.

We present an optical sensing platform on a smartphone for high-throughput screening immunoassays. For the first time, a designed microprism array is utilized to achieve a one-time screening of 64 samples. To demonstrate the capability and the reliability of this optical sensing platform on smartphone, human interleukin 6 (IL-6) protein and six types of plant viruses are immunoassayed. The ability of quantification is shown by a sigmoidal dose-response curve fitting to analyze IL-6 protein. The accuracy in measuring the concentrations of IL-6 protein achieves 99.1%. On the other hand, to validate on-field immunoassays by our device, a total of 1030 samples are assayed using three immunoassay methods to detect six types of plant viruses. The accuracy is up to 96.2-99.9%; in addition, there is a high degree of agreement with lab instruments. The total cost for this high-throughput optical screening platform is ∼$50 USD. The reading time is only 2 s for 64 samples. The size is just as big as a portable hard drive. Our optical sensing platform on the smartphone offers a route toward in situ high-throughput screening immunoassays for viruses, pathogens, biomarkers, and toxins by decentralizing laboratory tests. With this mobile point-of-care optical platform, the spread of disease can be timely stopped within a very short turnaround time.

Rapid method for fabricating polymeric biconvex parabolic lenslets.

Microlenslets as well as microlens arrays have shown tremendous attractions and successes in miniature optical systems in recent decades. However, the fabrication methods for microlenslets and microlenslet arrays are limited. In this Letter, a rapid and low-cost method for fabricating polymeric biconvex lenslets is presented. This newly developed process is simply based on wetting behavior at interface and is able to produce high-quality biconvex lenslets with controllable size and shape. This technology will greatly simplify the production process and reduce the manufacturing costs for micro-optics.

[Expression and regulatory mechanism of microRNA-155 in the villi of patients with unexplained recurrent spontaneous abortion patients].

OBJECTIVE: To study the expression and the mechanism of miR-155in the villi of patients with unexplained recurrent spontaneous abortion (URSA). METHODS: The expression of miR-155 in the villi of 36 cases with URSA (URSA group) and 25 women with normal early pregnancy (control group) were detected by stem-loop real-time reverse transcription (RT) qPCR.Expression of hypoxia inducible factor-1 (HIF-1α), vascular endothelial cell growth factor (VEGF) and micro lymphatic vessel density (MVD) in the villi of were measured by immnohistochemical staining among two groups. RESULTS: (1)miR-155 expression:the mean miR-155 expression were 1.456 (0.489, 2.459) in URSA group and 2.833 (1.740, 3.794) in control group, which reached statistical difference (P < 0.05). The mean expression of miR-155 of 1.683 (0.902, 2.459) in URSA group with abortion times ( ≤ 3) was significantly higher than 1.229 (0.489, 1.719) in URSA group with more than 4 times abortion (P < 0.05). (2) Indexes :the expression of HIF-1α, VEGF and MVD value were 121 ± 12, 134 ± 12, 36 ± 6 in URSA group and 99 ± 10, 109 ± 10, 28 ± 4 in control group, which reached statistical difference (P < 0.01). The expression of HIF-1α, VEGF and MVD value of 119 ± 12, 134 ± 12, 35 ± 5 in URSA group with less than 3 times abortion was significantly lower than 128 ± 12, 138 ± 12, 43 ± 6 in URSA group with more than 4 times abortion (P < 0.01). CONCLUSIONS: The expression of miR-155 and HIF-1α is topically stimulated by oxygen signal.HIF-1α adjusts the transcription and translation of VEGF, which together involved in placental trophoblast invasion and placental angiogenesis. The low expression of miR-155 could interfere with expression of HIF-1α and VEGF, which might be involved in villous vascular dysplasia in URSA.

Glucocorticoid activates STAT3 and NF-κB synergistically with inflammatory cytokines to enhance the anti-inflammatory factor TSG6 expression in mesenchymal stem/stromal cells.

Glucocorticoid (GC) is essential for maintaining immune homeostasis. While GC is known to regulate the expression of genes related to inflammation in immune cells, the effects of GC, especially in the presence of inflammation, on non-immune cells remain largely unexplored. In particular, the impact of GC on inflammatory cytokine-induced immune modulatory responses of tissue stromal cells is unknown, though it has been widely used to modulate tissue injuries. Here we found that GC could enhance the expression of TSG6, a vital tissue repair effector molecule, in IFNγ and TNFα treated human umbilical cord (UC)-MSCs. NF-κB activation was found to be required for GC-augmented TSG6 upregulation. STAT3, but not STAT1, was also found to be required for the TSG6 upregulation in MSCs exposed to IFNγ, TNFα and GC. Moreover, the phosphorylation (activation) of STAT3 was attenuated when NF-κB was knocked down. Importantly, human UC-MSCs pretreated with a cocktail containing GC, IFNγ, and TNFα could significantly enhance the therapeutic effect of human UC-MSCs in an acute lung injury mouse model, as reflected by reduced infiltration of immune cells and down-regulation of iNOS in macrophages in the lung. Together, the findings reveal a novel link between GR, NF-κB and STAT3 in regulating the immunomodulatory and regenerative properties of MSCs, providing novel information for the understanding and treatment of inflammatory conditions.

A specific enterotype derived from gut microbiome of older individuals enables favorable responses to immune checkpoint blockade therapy.

Immunotherapy has revolutionized cancer treatment, but inconsistent responses persist. Our study delves into the intriguing phenomenon of enhanced immunotherapy sensitivity in older individuals with cancers. Through a meta-analysis encompassing 25 small-to-mid-sized trials of immune checkpoint blockade (ICB), we demonstrate that older individuals exhibit heightened responsiveness to ICB therapy. To understand the underlying mechanism, we reanalyze single-cell RNA sequencing (scRNA-seq) data from multiple studies and unveil distinct upregulation of exhausted and cytotoxic T cell markers within the tumor microenvironment (TME) of older patients. Recognizing the potential role of gut microbiota in modulating the efficacy of immunotherapy, we identify an aging-enriched enterotype linked to improved immunotherapy outcomes in older patients. Fecal microbiota transplantation experiments in mice confirm the therapeutic potential of the aging-enriched enterotype, enhancing treatment sensitivity and reshaping the TME. Our discoveries confront the prevailing paradox and provide encouraging paths for tailoring cancer immunotherapy strategies according to an individual's gut microbiome profile.

3D-3D dentition superimposition for individual identification: A study of an Eastern Chinese population.

Recently, 3D dental intraoral scanning technology has been developed rapidly and applied widely in everyday dental practice. Since 3D dental scanning could provide valuable personal information, it enabled researchers to develop novel procedures for individual identification through 3D-3D dentition superimposition. This study aimed to test the applicability of this method in an Eastern Chinese population and propose a threshold for personal identification. For this purpose, 40 volunteers were recruited, and the initial 80 (upper and lower) 3D intraoral scans (IOS) were collected. After one year, 80 IOS of these volunteers were repeatedly collected. In addition, the other 120 IOS of 60 patients were extracted from the database. The 3D models were trimmed, aligned, and superimposed via Geomagic Control X software, and then the root mean square (RMS) value of point-to-point distance between the two models was calculated. The superimposition of two IOS belonging to the same individual was considered as a match, and superimposition of two IOS belonging to different individuals was considered as a mismatch. Totally, superimpositions of 80 matches and 3120 mismatches were obtained. Intra- and inter-observer errors were assessed through the calculation of relative technical error of measurement (rTEM). Mann-Whitney U test verified possible statistically significant differences between matches and mismatches (P < 0.05). The rTEM of intra- and inter-observer repeatability analyses was lower than 4.7 %. The range of RMS value was 0.05-0.18 mm in matches and 0.72-2.28 mm in mismatches without overlapping. The percentage of accurate identification reached 100 % in blind test through an arbitrary RMS threshold of 0.45 mm. The results indicated that individual identification through the 3D-3D dentition superimposition was effective in Eastern Chinese population. Successful identification could be achieved with high probability when the RMS value of the point-to-point distance of two dentitions is <0.45 mm.

AKT/foxo3a signal pathway mediates the protective mechanism of resveratrol on renal interstitial fibrosis and oxidative stress in rats with unilateral ureteral obstruction.

OBJECTIVE: To explore whether protein kinase B (serine/threonrine kinase, AKT)/forkhead box protein O3a (foxo3a) pathway mediates the protective mechanism of resveratrol (RSV) on renal interstitial fibrosis (RIF) and oxidative stress. METHODS: Sprague-Dawley (SD) rats were grouped into Sham group, unilateral ureteral obstruction (UUO) group and UUO + RSV group. HE staining was used to test the pathological damage of RIF intervened by RSV, biochemical analyzer was used to measure serum renal injury indexes (creatinine, Cr, blood urea nitrogen, Bun), and enzyme-linked immunosorbent assay (ELISA) was used to detect oxidative stress indexes (malondialdehyde, MDA; glutathione, GSH; superoxide dismutase, SOD). AKT/FoxO3a signaling pathway markers and renal interstitial indexes were measured by western blot analysis. RESULTS: Compared with Sham group, HE staining in UUO group showed significant RIF pathological damage; Cr and Bun indexes were increased, and AKT/FoxO3a signal pathway was activated, as indicated by increased p-AKT/AKT and p-FoxO3a/FoxO3a; TGF-ß1 and α-SMA protein levels in fibrosis indexes were increased, while E-cadherin decreased; MDA was increased, GSH and SOD were decreased in oxidative stress indexes, while those in UUO + RSV group were improved. CONCLUSION: AKT/foxo3a signaling pathway mediates the protective mechanism of RSV on RIF and oxidative stress in UUO rats, and RSV can improve RIF and oxidative stress in UUO rats by inhibiting AKT/foxo3a signaling pathway.

Soybean diacylglycerol regulates lipid metabolism in D-galactose-induced aging rats by altering gut microbiota and gene expression of colonic epithelial cells.

Lipid metabolism is closely related to the health of aging bodies and its disorder often leads to cardiovascular diseases and chronic diseases. Dietary fat is one of the important sources of body fat, which affects the body's lipid metabolism. However, how dietary fat affects lipid metabolism in aging bodies has not been reported. Thus, the effects of soybean diacylglycerol (DAG) on lipid metabolism in D-galactose-induced aging rats were investigated by detecting the serum biochemical indexes, hepatocyte morphology, gut microbiota changes, and gene expression of colonic epithelial cells. The results showed that DAG alleviated the lipid metabolism disorders, and the hepatocyte morphology of aging rats fed DAG was normal. 16S rDNA analysis showed that DAG restored Eisenbergiella and Veillonella that were missing in aging rats. The relative abundances of Romboutsia and Ruminococcus_2 decreased and the relative abundance of Lachnospiraceae NK4A136 group increased significantly with the influence of DAG (P < 0.05). Gene expression profiles showed that the gene expression of colon epithelial cells was altered by DAG and DAG downregulated the genes Lipe and Fabp4 related to the lipolysis of adipocytes. In conclusion, DAG regulated the lipid metabolism of aging rats by regulating gut microbiota and gene expression of colonic epithelial cells.

Dynamic monitoring and a clinical correlation analysis of the serum vitamin A, D, and E levels in children with recurrent respiratory tract infections.

OBJECTIVE: To investigate the correlation of the serum vitamin A, D, and E (VA, VD, and VE) levels with the occurrence and development of recurrent respiratory tract infections (RRTIs). METHODS: A total of 129 children with respiratory tract infections (RTIs) treated in our hospital from January 2018 to February 2020 (the RTIs group) and 50 healthy children undergoing physical examinations (the control group) in our hospital were recruited as the study cohort. The serum VA, VD, and VE levels were measured upon admission (the active phase) and at two weeks after discharge (the stable phase). The serum VA, VD, and VE levels in the children with RRTIs were compared with the levels in the control group, and the correlation between these three vitamins and the occurrence and development of RRTIs was analyzed. RESULTS: The RRTIs group and the RTIs group witnessed markedly lower serum VA, VD, VE, and humoral immunity index levels, including IgG, IgA, and IgM, compared to the control group, with an apparent lower outcome in the RRTIs group than in the RTIs group. The serum levels of the above indexes in the RRTIs children were reduced in the active phase compared with the stable phase. A Pearson correlation analysis showed a positive correlation between VA and IgA. A multivariate logistic regression analysis revealed that a low BMI (Body mass index), prematurity, VA deficiency, VD deficiency, and VE deficiency were the risk factors for RRTIs in children, and outdoor activity was the protective factor. CONCLUSION: The VA, VD, and VE levels are closely related to RRTIs in children. It is important to determine and supplement the VA, VD, and VE levels to prevent RTIs in children.

Clinical Monitoring of Serum Levels of Vitamins A, D and E in Children with Recurrent Respiratory Tract Infections of Different Ages: A Clinical Controlled Trial.

Objective: To study serum levels of vitamins A, D and E in children with recurrent respiratory tract infections of different ages and the correlation. Methods: The clinical data of two groups of children of different ages were collected. The serum levels and deficiencies of vitamins A, D and E in children were statistically analyzed. Results: The proportions of premature infants, low body weight infants, special physique, hospitalization history, hypocalcemia, living in a bungalow, and daily outdoor activities in less than 30 minutes in the case group were higher than those in the control group (χ 2=4.507, 5.165, 7.040, 14.907, 4.267, 33.800, 4.507, 8.571, P < 0.05). The serum levels of vitamins A, D and E of children aged 0-1, 2-5, and 6-12 in the case group were lower than those in the control group (P < 0.05). Compared with the control group, the serum vitamin A level of children in the case group was lower (t = 2.631, P < 0.05), and the deficiency rate was higher (χ 2=24.200, P < 0.05). Conclusion: Serum levels of vitamins A, D and E, which are related to birth mode, physical fitness, hospitalization history, hypocalcemia, vitamin deficiency, living environment, and daily outdoor activity time, vary in children with recurrent respiratory tract infections of different ages, and are lower in children with recurrent respiratory tract infections than in healthy children.

Metabolomic analysis and oxidative stress response reveals the toxicity in Escherichia coli induced by organophosphate flame retardants tris(2-chloroethyl) phosphate and triphenyl phosphate.

Organophosphate flame retardants (OPFRs) are emerging environmental pollutants that are increasingly being used in consumer commodities. The adverse effects on biota induced by tris(2-chloroethyl) phosphate (TCEP) and triphenyl phosphate (TPHP) have become a growing concern. Unfortunately, toxic mechanisms at the molecular level for OPFRs in organisms are still lacking. Herein, Escherichia coli (E.coli) was exposed to TCEP and TPHP for 24 and 48 h to reveal oxidative stress response and molecular toxicity mechanisms. The results indicated that promotion of ROS overload occurred at higher dosages groups. The levels of SOD and CAT were significantly elevated along with the increase of MDA attributed to lipid peroxidation. Additionally, apoptosis rates increased, accompanied by a decline in membrane potential and Na+/K+-ATPase and Ca2+/Mg2+-ATPase contents, signifying that E. coli cytotoxicity induced by TCEP and TPHP was mediated by oxidative stress. Based on metabolomic analysis, different metabolic pathways were disrupted, including glycolysis/gluconeogenesis, pentose phosphate metabolism, purine metabolism, glutathione metabolism, amino acid biosynthesis, butanoate metabolism, alanine and aspartate metabolism. Most differentially expressed metabolites were downregulated, indicating an inhibitory effect on metabolic functions and key metabolic pathways. These findings generated new insights into the potential environmental risks of OPFRs in aquatic organisms.

Mesenchymal stem cells alleviate systemic sclerosis by inhibiting the recruitment of pathogenic macrophages.

Systemic sclerosis (SSc) is a recalcitrant autoimmune disease for which there is no cure. Mesenchymal stem cell (MSC)-based treatment has emerged as a promising therapeutic option for several autoimmune diseases. Previously, we found that the immunoregulatory potential of MSCs can be greatly enhanced by IFN-γ and TNF-α. Here, we found that IFN-γ- and TNF-α-pretreated MSCs significantly alleviated skin fibrosis in a bleomycin (BLM)-induced SSc model. Macrophages were found to be the predominant profibrotic immune cell population in the pathogenesis of SSc. The accumulation of macrophages was significantly decreased by MSC treatment. Importantly, MSCs primarily reduced the population of maturing macrophages with high CCR2 expression by inhibiting the generation of CCL2 from fibroblasts and macrophages. This finding may help to improve MSC-based clinical treatments for SSc patients.