Oxidative stress mediates the associations between phthalate exposures and thyroid cancer/benign nodule risk.

Epidemiological studies have suggested that phthalate exposures are associated with increased risks of thyroid cancer and benign nodule, while the underlying mechanisms are largely unknown. Here, we explored the mediation effects of oxidative stress (OS) biomarkers in the associations between phthalate exposures and the risks of thyroid cancer and benign nodule. Urine samples collected from 143 thyroid cancer, 136 nodule patients, and 141 healthy controls were analyzed for 8 phthalate metabolites and 3 OS biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), and 8-iso-prostaglandin F2α (8-isoPGF2α)]. Multivariable linear or logistic regression models were used to explore the associations of OS biomarkers with phthalate metabolite concentrations and the risks of thyroid cancer and nodule. The mediation role of OS biomarkers was also investigated. Urinary monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethylhexyl) phthalate (MEHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were positively associated with at least 2 OS biomarkers (all P-values<0.01), and part of these positive associations varied in different subgroups. All 3 OS biomarkers were positively associated with the risks of thyroid nodule and cancer (P-values<0.001). The mediation analysis showed that OS biomarkers significantly mediated the associations between urinary MEHOP concentration and nodule, as well as between urinary MMP, MEHP, and MEHHP concentrations and cancer and nodule, with the estimated proportions of mediation ranging from 15.8% to 85.6%. Our results suggest that OS is a potential mediating mechanism through which phthalate exposures induce thyroid carcinogenesis and nodular formation.

Exploration of the oxygen reduction reaction activity of four transition metal borates: synthesis, structure and characterization.

Four new transition metal borates, [Co(1-MI)2]·B5O7(OH)3 (1, 1-MI = 1-methylimidazole), Co2(PZ)8(SO4)2·2H3BO3 (2, PZ = pyrazole), K7{(BO3)Co[B12O18(OH)6]}·H2O (3) and K2{[Ni(PY)2]2·[(C4H2O6)2B]}2 (4, PY = pyridine), have been successfully synthesized by a mild method. Their structures were determined by X-ray single crystal diffraction. These compounds were further characterized by FTIR, PXRD and UV-vis-NIR. It is worth noting that the catalytic properties of catalysts based on these four borates were explored, and that organically templated borate 1- and 2-based catalysts showed better ORR catalytic performance compared to 3- and 4-based catalysts. This may be caused by the supramolecular skeletons of 1 and 2 providing sufficient space and porosity.

Nitrate_dependent suberization regulates cadmium uptake and accumulation in maize.

In this study, effect of nitrate-dependent suberization in maize root on cadmium (Cd) uptake and accumulation was investigated. Suberization in maize roots was significantly lower in plants grown with a high nitrate supply compared with low nitrate. This decrease was seen in the total amount of suberin, in which the aliphatic suberin amount was significantly decreased, whereas no difference in aromatic suberin content between different N-treatments. RNA-sequencing showed that suberin biosynthesis genes were upregulated in low nitrate treatment, which correlated well with the increased suberin content. Bioimaging and xylem sap analysis showed that reduced exodermal and endodermal suberization in roots of plants grown under high nitrate promoted radial Cd transport along the crown root. The enhanced suberization in crown roots of plants grown in low nitrate restricted the radial transport of Cd from epidermis to cortex via decreased accessibility to Cd related transporters at the plasmalemma. Also, under low nitrate supply, the Cd transport gene ZmNramp5 was upregulated in the crown root, which may enhance Cd uptake by root tip where exodermis and endodermis were not fully suberized. These results suggest that high nitrate supply enhances Cd uptake and radial transport in maize roots by reducing exodermal and endodermal suberization.

Metabolomic study combined with the low-level light therapy of Chinese acupuncture points and combined oral contraceptives in treatment of primary dysmenorrhea: A prospective, multicenter, randomized controlled study.

Objective: To compare the changes of metabolites between Low-level light therapy (LLLT) and combined oral contraceptive (COC) after treatment of primary dysmenorrhea (PD), and to compare and analyze the biological and biochemical effects of the two treatments by analyzing the differences in metabolite profiles. Methods: A multicenter, double-blind, prospective, parallel, randomized controlled study was conducted on 69 women aged 16-35 years old with PD who were randomly divided into COC treatment group or LLLT treatment group. Low-level light therapy with light-emitting diodes (LED) was applied on two acupoints named "Guanyuan" (CV4) and "Qihai" (CV6). After 12 weeks of treatment intervention, blood samples were collected before and after treatment for metabolomic analysis. We used UPLC-MS/MS analysis to compare the differences in metabolite changes between LLLT and COC before and after treatment. Results: 76 differential metabolites were detected in the LLLT group, and 92 differential metabolites were detected in the COC group, which were up-regulated or down-regulated (p < 0.001). Prostaglandin D2 (PG D2) was down-regulated and biliverdin was up-regulated after LLLT treatment, 4a-Hydroxytetrahydrobiopterin, Prostaglandin D2, 5-Hydroxy-l-tryptophan, Cholic acid were down-regulated and cortisol was up-regulated after COC treatment, and the differences were statistically significant. Cortisol and testosterone glucuronide in LLLT group were significantly lower than those in COC group. The metabolic pathways affected were glycerophospholipid metabolism, linoleic acid metabolism and arachidonic acid metabolism in the LLLT group, and glycerophospholipid metabolism, folate biosynthesis, arachidonic-acid-metabolism, and tryptophan metabolism in the COC group. The differential metabolic pathway were linoleic acid metabolism, steroid hormone biosynthesis, and alpha-Linolenic acid metabolism after the comparison of LLLT with COC. Conclusion: LLLT and COC might relieve dysmenorrhea by down-regulating PGD2, and LLLT might also relieve dysmenorrhea by up-regulating biliverdin. The level of cortisol and testosterone glucuronide after LLLT treatment was lower than that after COC treatment, which might lead to the difference in the clinical efficacy of the two treatments for dysmenorrhea.

Enzyme-Assisted Nucleic Acid Amplification in Molecular Diagnosis: A Review.

Infectious diseases and tumors have become the biggest medical challenges in the 21st century. They are driven by multiple factors such as population growth, aging, climate change, genetic predispositions and more. Nucleic acid amplification technologies (NAATs) are used for rapid and accurate diagnostic testing, providing critical information in order to facilitate better follow-up treatment and prognosis. NAATs are widely used due their high sensitivity, specificity, rapid amplification and detection. It should be noted that different NAATs can be selected according to different environments and research fields; for example, isothermal amplification with a simple operation can be preferred in developing countries or resource-poor areas. In the field of translational medicine, CRISPR has shown great prospects. The core component of NAAT lies in the activity of different enzymes. As the most critical material of nucleic acid amplification, the key role of the enzyme is self-evident, playing the upmost important role in molecular diagnosis. In this review, several common enzymes used in NAATs are compared and described in detail. Furthermore, we summarize both the advances and common issues of NAATs in clinical application.

Aptamers in cancer therapy: problems and new breakthroughs.

Aptamers, a class of oligonucleotides that can bind with molecular targets with high affinity and specificity, have been widely applied in research fields including biosensing, imaging, diagnosing, and therapy of diseases. However, compared with the rapid development in the research fields, the clinical application of aptamers is progressing at a much slower speed, especially in the therapy of cancer. Obstructions including nuclease degradation, renal clearance, a complex selection process, and potential side effects have inhibited the clinical transformation of aptamer-conjugated drugs. To overcome these problems, taking certain measures to improve the biocompatibility and stability of aptamer-conjugated drugs in vivo is necessary. In this review, the obstructions mentioned above are thoroughly discussed and the methods to overcome these problems are introduced in detail. Furthermore, landmark research works and the most recent studies on aptamer-conjugated drugs for cancer therapy are also listed as examples, and the future directions of research for aptamer clinical transformation are discussed.

Impact of coronary computed tomography angiography-derived fractional flow reserve based on deep learning on clinical management.

Background: To examine the value of coronary computed tomography angiography (CCTA)-derived fractional flow reserve based on deep learning (DL-FFRCT) on clinical practice and analyze the limitations of the application of DL-FFRCT. Methods: This is an observational, retrospective, single-center study. Patients with suspected coronary artery disease (CAD) were enrolled. The patients underwent invasive coronary angiography (ICA) examination within 1 months after CCTA examination. And quantitative coronary angiography (QCA) was performed to evaluate the area stenosis rate. The CCTA data of these patients were retrospectively analyzed to calculate the FFRCT value. Results: A total of 485 lesions of coronary arteries in 229 patients were included in the analysis. Of the lesions, 275 (56.7%) were ICA-positive, and 210 (43.3%) were FFRCT-positive. The discordance rate of the risk stratification of FFRCT for ICA-positive lesions was 33.1% (91) and that for ICA-negative lesions was 12.4% (26). 14.6% (7/48) patients with mild to moderate coronary stenosis in ICA have functional ischemia according to FFRCT positive indications. In addition, hemodynamic analysis of severely calcified, occluded, or small (< 2 mm in diameter) coronary arteries by DL-FFRCT is not so reliable. Conclusion: This study revealed that most patients with ICA negative did not require further invasive FFR. Besides, some patients with mild to moderate coronary stenosis in ICA may also have functional ischemia. However, for severely calcified, occluded, or small coronary arteries, treatment strategy should be selected based on ICA in combination with clinical practice.

Ultra-processed food intake and risk of depression: a systematic review / Ingestión de alimentos ultraprocesados y riesgo de depresión: revisión sistemática

Objective: to conduct a systematic review of the observational studies analyzing the association between ultra-processed food (UPF) intake and the risk of depression. Design: the search adhered to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); a search for observational studies published until June 2020 was performed in PubMed, Embase, Cochrane Library, and Web of Science databases, followed by additional manual searches. Eight reviewers, working independently in teams of two, screened studies for eligibility, extracted data, and assessed risk of bias. We resolved disagreements through discussion or, if necessary, through adjudication by a third (LH). And the study assessed cross-sectional studies using the Agency for Healthcare Research and Quality (AHRQ) methodological checklist and cohort and case-control studies using the Newcastle-Ottawa Scale (NOS) for quality. We used a tabular format to summarize the articles. Results: twenty-eight studies evaluating UPF intake and risk of depression were finally selected, 21 of which had a cross-sectional design, 6 studies had a cohort design, and 1 had a case-control design. Of these, 4 cohort studies and 17 cross-sectional studies found that consumption of UPF were positively associated with depression or depressive symptoms. Conclusions: our review demonstrated that most studies included in the systematic review showed that UPF consumption is associated with the risk of depression. Future studies should consider the use of validated food intake assessments and standardized depression assessment methods to promote comparability between studies. (AU)

Objetivo: realizar una revisión sistemática de los estudios observacionales que analizan la asociación entre la ingesta de alimentos ultraprocesados (UPF) y el riesgo de depresión. Material y métodos: la búsqueda se adhirió a las directrices Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); se realizó una búsqueda de estudios observacionales publicados hasta junio de 2020 en las bases de datos PubMed, Embase, Cochrane Library y Web of Science, seguida de búsquedas manuales adicionales. Ocho revisores, que trabajaron de forma independiente en equipos de dos, seleccionaron los estudios para su elegibilidad, extrajeron los datos y evaluaron el riesgo de sesgo. Los desacuerdos se resolvieron a través de la discusión o, si era necesario, a través de la adjudicación de un tercero. Se evaluaron los estudios transversales mediante la lista de comprobación metodológica de la Agency for Healthcare Research and Quality (AHRQ) y los estudios de cohortes y de casos y controles mediante la escala Newcastle-Ottawa (NOS) para la calidad. Se utilizó un formato tabular para resumir los artículos. Resultados: finalmente se seleccionaron 28 estudios que evaluaban la ingesta de UPF y el riesgo de depresión, 21 de los cuales tenían un diseño transversal, 6 un diseño de cohortes y 1 un diseño de casos y controles. De ellos, 4 estudios de cohortes y 17 estudios transversales encontraron que el consumo de UPF se asociaba positivamente con la depresión o los síntomas depresivos. Conclusiones: nuestra revisión demostró que la mayoría de los estudios incluidos en la revisión sistemática mostraron que el consumo de UPF está asociado con el riesgo de depresión. Los estudios futuros deberían considerar el uso de evaluaciones validadas del consumo de alimentos y métodos estandarizados de evaluación de la depresión para promover la comparabilidad entre los estudios. (AU)

[Effect of processing method on chemical constituents of Rehmanniae Radix: based on UHPLC-LTQ-Orbitrap MS].

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.

Construction and Verification of the Molecular Subtype and a Novel Prognostic Signature Based on Inflammatory Response-Related Genes in Uveal Melanoma.

The significance of inflammation in tumorigenesis and progression has become prominent. This study aimed to construct and validate the molecular subtype and a novel prognostic signature based on inflammatory response-related genes in uveal melanoma (UM). Patients from the TCGA, GSE84976, and GSE22138 UM cohorts were enrolled. According to the consensus cluster analysis, patients were divided into two molecular subtypes, namely IC1 and IC2. Survival curves showed that patients in IC1 had a better prognosis. The IC2 subgroup had higher levels of immune cell infiltration and more enriched immunological pathways. There were statistical differences in the immune-inflammation microenvironment, immune checkpoint genes expression, and drug sensitivity. The prognostic signature constructed based on inflammatory response-related genes exhibited a stable predictive power. Multivariate analysis confirmed that the signature was a prognostic factor independent of clinical characteristics. Functional analyses showed that the high-risk group was associated with immunological response, inflammatory cell activation, and tumor-related signal pathways. The riskscore had a negative relationship with tumor purity and was positively correlated with immune and stromal scores. Furthermore, the prognostic signature could sensitively predict the response to drug treatments. In conclusion, the prognostic signature might aid in stratifying patients at risk premised on the prognosis and immunotherapy sensitivity.

STING mediates SU5416/hypoxia-induced pulmonary arterial hypertension in rats by regulating macrophage NLRP3 inflammasome activation.

BACKGROUND: The NLRP3 inflammasome in macrophages is known to promote infection-related vascular growth, and NLRP3 inflammasome activation interacts with PAH. STING is a crucial inflammatory reaction link that can increase the overexpression of NLRP3. However, the expression and effect of STING in PAH have not been elucidated. We examined the expression and articulation of STING in PAH and researched its hidden mechanism. METHODS: A SU5416 plus hypoxia (Su/Hy)-induced rat model of PAH was constructed to examine STING activation. Su/Hy induced PAH rats were given a prophylactic injection of STING the inhibitor C-176. After modeling, hemodynamic changes, right ventricular hypertrophy index, lung morphological features, inflammasome activation, and proinflammatory cytokine secretion levels were assessed. In addition, the STING agonist DMXAA or inhibitor C-176 was used to interfere with LPS-induced BMDMs, NLRP3 inflammasome activation and cytokine secretion were examined, and the effect on PASMCs was evaluated in a coculture system. RESULTS: STING expression increased significantly in the lung tissue of Su/Hy-treated PAH rats compared with normoxia-treated rats. Moreover, STING inhibitors can alleviate the Su/Hy-induced increase in pulmonary artery pressure and restrain the activation of the NLRP3 inflammasome and proinflammatory cytokines. In vitro experiments confirmed that STING affected the expression of the NLRP3 inflammasome and the secretion of inflammatory cytokines in BMDMs and promoted the proliferation of PASMCs in the coculture system. CONCLUSION: Our study shows that STING is activated in Su/Hy-induced PAH and boosts the actuation of the macrophage NLRP3 inflammasome to advance the inflammatory response and vascular proliferation in rats with Su/Hy-induced pulmonary hypertension.

Optimizing the operation strategy of a combined cooling, heating and power system based on energy storage technology.

Energy storage technology is the key to achieving a carbon emission policy. The purpose of the paper is to improve the overall performance of the combined cooling, heating and power-ground source heat pump (CCHP-GSHP) system by the battery. A new operation strategy (the two-point operation) is proposed by controlling the power generation unit work. The power generation unit has two operation modes of non-operation and rated efficiency operation by the storage electricity battery. The new operation strategy is compared with the traditional CCHP-GSHP that without a battery. The optimization goals include the primary energy saving ratio, the reduction ratio of carbon dioxide emissions, and the annual total cost saving ratio. The independent GSHP system is used as a reference system. Multipopulation genetic algorithms are selected to achieve the problem of optimization. A hotel building is selected for a case study. The optimal configuration of the coupling system is computed following the electric load strategy. Finally, the results show that the CCHP-GSHP system has a better performance under the new operation strategy compared with the traditional CCHP-GSHP (the primary energy saving ratio increases by 5.5%; the annual carbon dioxide emission reduction ratio increases by 1%; the annual total cost reduction ratio increases by 5.1%). This paper provides reference and suggestions for the integration and operation strategy of CCHP-GSHP in the future.

Dynamic variation of Paris polyphylla root-associated microbiome assembly with planting years.

MAIN CONCLUSION: P. polyphylla selectively enriches beneficial microorganisms to help their growth. Paris polyphylla (P. polyphylla) is an important perennial plant for Chinese traditional medicine. Uncovering the interaction between P. polyphylla and the related microorganisms would help to utilize and cultivate P. polyphylla. However, studies focusing on P. polyphylla and related microbes are scarce, especially on the assembly mechanisms and dynamics of the P. polyphylla microbiome. High-throughput sequencing of the 16S rRNA genes was implemented to investigate the diversity, community assembly process and molecular ecological network of the bacterial communities in three root compartments (bulk soil, rhizosphere, and root endosphere) across three years. Our results demonstrated that the composition and assembly process of the microbial community in different compartments varied greatly and were strongly affected by planting years. Bacterial diversity was reduced from bulk soils to rhizosphere soils to root endosphere and varied over time. Microorganisms benefit to plants was selectively enriched in P. polyphylla roots as was its core microbiome, including Pseudomonas, Rhizobium, Steroidobacter, Sphingobium and Agrobacterium. The network's complexity and the proportion of stochasticity in the community assembly process increased. Besides, nitrogen metabolism, carbon metabolism, phosphonate and phosphinate metabolism genes in bulk soils increased over time. These findings suggest that P. polyphylla exerts a selective effect to enrich the beneficial microorganisms and proves the sequential increasing selection pressure with P. polyphylla growth. Our work adds to the understanding of the dynamic processes of plant-associated microbial community assembly, guides the selection and application timing of P. polyphylla-associated microbial inoculants and is vital for sustainable agriculture.

miR-27b-3p inhibits estrogen secretion of goose granulosa cells by targeting CYP1B1 through the AMPK signaling pathway.

Although miR-27b-3p has been evidenced to regulate the proliferation, apoptosis, and differentiation of a variety of mammalian cell types, its actions and mechanisms on ovarian cell steroidogenesis remains largely unknown in both mammalian and avian species. In this study, we aimed to determine the expression profiles of miR-27b-3p in granulosa cell layers during goose ovarian follicle development and to reveal its actions on estrogen (E2) secretion of goose granulosa cells as well as the underlying regulatory mechanisms. It was observed that miR-27b-3p was ubiquitously expressed throughout follicle development but exhibited much higher levels in hierarchical- than in prehierarchical follicles. In cultured granulosa cells from the fourth through second largest preovulatory (F4-F2) follicles of goose, up- and downregulation of miR-27b-3p by using its mimic and inhibitor significantly decreased and increased E2 secretion, respectively. Meanwhile, the mRNA levels of STAR and CYP19A1 were significantly reduced while those of CYP11A1 and 3ßHSD were elevated in the mimic-transfected granulosa cells. By comparison, downregulation of miR-27b-3p enhanced the mRNA levels of STAR but had no significant effects on those of CYP19A1, CYP11A1, and 3ßHSD. Results from bioinformatic prediction and luciferase reporter assay demonstrated that CYP1B1 was a downstream target of miR-27b-3p. Although the siRNA-mediated downregulation of CYP1B1 did not significantly change E2 secretion by goose granulosa cells, it reduced the mRNA levels of STAR and CYP19A1 as well as those of LKB1 and AMPKα, which are involved in the AMPK signaling pathway. Taken together, these data suggest that miR-27b-3p plays an inhibitory role in E2 secretion by goose F4-F2 granulosa cells, at least in part, by targeting CYP1B1 through the AMPK signaling pathway.

Sex Differences in D-Dimer and Critical Illness in COVID-19 Patients: A Systematic Review and Meta-analysis.

Background: Observed sex differences in COVID-19 outcomes suggest males are more likely to experience critical illness and mortality. Thrombosis is common in severe COVID-19 and D-dimer is a significant marker for COVID-19 severity and mortality. It is unclear whether D-dimer levels differ between males and females and the effect of D-dimer levels on disease outcomes remains under investigation. Objective: We aimed to evaluate the sex difference in D-dimer level among hospitalized COVID-19 patients and the effect of sex and D-dimer level on disease outcomes. Methods: We meta-analyzed papers reporting D-dimer level in male and female hospitalized COVID-19 patients, until October 2021, using random-effects. Primary outcomes were mortality, critical illness, and thrombotic complications. Results: 11682 patients from 10 studies were analysed (N=5606 (55.7%) male, N=5176 (44.3%) female). Males had significantly higher odds of experiencing mortality (OR=1.41, 95% CI: [1.25, 1.59], p = <0.001, I2 = 0%) and critical illness (OR=1.76, 95% CI: [1.43, 2.18], p = <0.001, I2 = 61%). Mean D-dimer level was not significantly different between males and females (MD=0.08, 95% CI: [-0.23, 0.40], p = 0.61, I2 = 52%). In subgroup analysis males had significantly higher odds of experiencing critical illness compared to females in both the 'higher' (p=0.006) and 'lower' (p=0.001) D-dimer subgroups. Conclusions: Males have significantly increased odds of experiencing poor COVID-19 outcomes compared to females. No sex difference was found in D-dimer level between male and female COVID-19 patients. The diversity in D-dimer reporting impacts data interpretation and requires further attention.

Maternal exposure to nitrosamines in drinking water during pregnancy and birth outcomes in a Chinese cohort.

Maternal exposure to regulated disinfection by-products (DBPs) during pregnancy has been linked with adverse birth outcomes. However, no human studies have focused on drinking water nitrosamines, a group of emerging unregulated nitrogenous DBPs that exhibits genotoxicity and developmental toxicity in experimental studies. This cohort study included 2457 mother-infant pairs from a single drinking water supply system in central China, and maternal trimester-specific and entire pregnancy exposure of drinking water nitrosamines were evaluated. Multivariable linear and Poisson regression models were used to estimate the associations between maternal exposure to nitrosamines in drinking water and birth outcomes [birth weight (BW), low birth weight (LBW), small for gestational age (SGA) and preterm delivery (PTD)]. Elevated maternal N-nitrosodimethylamine (NDMA) exposure in the second trimester and N-nitrosopiperidine (NPIP) exposure during the entire pregnancy were associated with decreased BW (e.g., ß = -88.6 g; 95% CI: -151.0, -26.1 for the highest vs. lowest tertile of NDMA; p for trend = 0.01) and increased risks of PTD [e.g., risk ratio (RR) = 2.16; 95% CI: 1.23, 3.79 for the highest vs. lowest tertile of NDMA; p for trend = 0.002]. Elevated maternal exposure of N-nitrosodiethylamine (NDEA) in the second trimester was associated with increased risk of SGA (RR = 1.80; 95% CI: 1.09, 2.98 for the highest vs. lowest tertile; p for trend = 0.01). Our study detected associations of maternal exposure to drinking water nitrosamines during pregnancy with decreased BW and increased risks of SGA and PTD. These findings are novel but require replication in other study populations.

Echocardiographic evaluation of left atrial strain for predicting iron overload in pediatric patients with ß-thalassemia with preserved ejection fraction.

Pediatric patients with ß-thalassemia (ß-TM) with preserved ejection fraction may experience early myocardial damage. This prospective study aimed to investigate left atrial (LA) function restructure in pediatric patients with ß-TM by two-dimensional speckle tracking echocardiography (2D-STE) and evaluate the value of LA strain for predicting myocardial iron overload (MIO). We recruited 50 ß-TM pediatric patients and 30 healthy children aged 3-14 years. The patients were assigned to a normal left ventricular (LV) lesion group (n = 20) and an enlarged LV lesion group (n = 30). Subjects all underwent echocardiography to measure conventional cardiac function parameters and LA strain parameters. The results displayed that LA reservoir strain (LASr), conduit strain (LAScd), contractile strain (LASct) and strain rate were significantly reduced in pediatric patients with ß-TM with preserved ejection fraction. LASr, LAScd, and LASct were negatively correlated with the E/e' ratio, of which LASr had the most significant correlation (r = - 0.69, P < 0.001). LASr and LASct correlated positively with T2* (r = 0.70 and 0.62, respectively, all P < 0.001). In the multiple regression, LASr and LASct were independent predictors for T2*. The areas under the curve for LASr and LASct were 0.87 (P < 0.001) and 0.78 (P = 0.004), respectively. Our results demonstrated that LA strains were dramatically impaired in pediatric patients with ß-TM, and LASr is an efficient indicator for detecting LV early diastolic dysfunction in ß-TM pediatric patients and reflects early myocardial damage. LASr and LASct were independently predictive of MIO, but LASr was a more sensitive predictor.

Selection and electrochemical-sensor application of an DNA-aptamer for methyl parathion detection.

An aptamer-based electrochemical sensor for methyl parathion (MP) detection is herein reported. The modified magnetic beads-systematic evolution of ligands by enrichment (MB-SELEX) was used to select the MP aptamer. After 14 rounds of selection, the aptamer (MPapta-6) with high affinity for MP was obtained, and its dissociation constant (Kd) was 39.66 ± 14.73 µM. Using the MPapta-6, the ultra-sensitive electrochemical sensor based on PLL-BP and AuNPs was constructed. The linear range of MP was 1-105 pM and detection limit (LOD) was as low as 0.49 pM. In addition, the application of the sensor in water samples was verified, and the recovery rate was 96.6%-103.5%. The results from this study showed that this strategy could be applied in practical detection.

AXL antibody and AXL-ADC mediate antitumor efficacy via targeting AXL in tumor-intrinsic epithelial-mesenchymal transition and tumor-associated M2-like macrophage.

The receptor tyrosine kinase AXL is an emerging driver of cancer recurrence, while its molecular mechanism remains unclear. In this study we investigated how AXL regulated the disease progression and poor prognosis in non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). We performed AXL transcriptome analysis from TCGA datasets, and found that AXL expression was significantly elevated in NSCLC and TNBC correlating with poor prognosis, epithelial-mesenchymal transition (EMT) and immune-tolerant tumor microenvironment (TME). Knockdown of AXL or treatment with two independent AXL antibodies (named anti-AXL and AXL02) all diminished cell migration and EMT in AXL-high expressing NSCLC and TNBC cell lines. In a mouse model of 4T1 TNBC, administration of anti-AXL antibody substantially inhibited lung metastases formation and growth, accompanied by reduced downstream signaling activation, EMT and proliferation index, as well as an increased apoptosis and activated anti-tumor immunity. We found that AXL was abundantly activated in tumor nodule-infiltrated M2-macrophages. A specific anti-AXL antibody blocked bone marrow-derived macrophage (BMDM) M2-polarization in vitro. Targeting of AXL in M2-macrophage in addition to tumor cell substantially suppressed CSF-1 production and eliminated M2-macrophage in TME, leading to a coordinated enhancement in both the innate and adaptive immunity reflecting M1-like macrophages, mature dendritic cells, cytotoxic T cells and B cells. We generated a novel and humanized AXL-ADC (AXL02-MMAE) employing a site-specific conjugation platform. AXL02-MMAE exerted potent cytotoxicity against a panel of AXL-high expressing tumor cell lines (IC50 < 0.1 nmol/L) and suppressed in vivo growth of multiple NSCLC and glioma tumors (a minimum efficacy dose<1 mg/kg). Compared to chemotherapy, AXL02-MMAE achieved a superior efficacy in regressing large sized tumors, eliminated AXL-H tumor cell-dependent M2-macrophage infiltration with a robust accumulation of inflammatory macrophages and mature dendritic cells. Our results support AXL-targeted therapy for treatment of advanced NSCLC and TNBC.

Retraction: Sericin hydrogels promote skin wound healing with effective regeneration of hair follicles and sebaceous glands after complete loss of epidermis and dermis.

Retraction of 'Sericin hydrogels promote skin wound healing with effective regeneration of hair follicles and sebaceous glands after complete loss of epidermis and dermis' by Chao Qi et al., Biomater. Sci., 2018, 6, 2859-2870, https://doi.org/10.1039/C8BM00934A.