Rational Design and Synthesis of Fe-Doped Co-Based Coordination Polymer Composite Photocatalysts for the Degradation of Norfloxacin and Ciprofloxacin.

The solar light-responsive Fe-doped Co-based coordination polymer (Fe@Co-CP) photocatalyst was synthesized under mild conditions. [Co(4-padpe)(1,3-BDC)]n (Co-CP) was first constructed using mixed ligands through the hydrothermal method. Then, Fe was introduced into the Co-CP framework to achieve the enhanced photocatalytic activity. The optimal Fe@Co-CP-2 exhibited excellent catalytic degradation performance for norfloxacin and ciprofloxacin under sunlight irradiation without auxiliary oxidants, and the degradation rates were 91.25 and 92.66% in 120 min. These excellent photocatalytic properties were ascribed to the generation of the Fe-O bond, which not only enhanced the light absorption intensity but also accelerated the separation efficiency of electrons and holes, and hence significantly improved the photocatalytic property of the composites. Meanwhile, Fe@Co-CP-2 displayed excellent stability and reusability. In addition, the degradation pathways and intermediates of antibiotic molecules were effectively analyzed. The free radical scavenging experiment and ESR results confirmed that •OH, •O2-, and h+ active species were involved in the catalytic degradation reaction; the corresponding mechanisms were deeply investigated. This study provides a fresh approach for constructing Fe-doped Co-CP-based composite materials as photocatalysts for degradation of antibiotic contaminants.

Distinct structure, assembly, and gene expression of microplankton in two Arctic estuaries with varied terrestrial inputs.

The Laptev Sea is a major Marginal Sea in the Western Arctic Ocean. The Arctic amplification brought by global warming influences the hydrological properties of rivers passing through the permafrost zone, which would alter the biological community structure at continental margin. In this study, the structure, assembly, and gene expression of planktonic microbial communities in two estuaries (Protoka Ularovskaya River Estuary, PURE; Lena River Estuary, LRE) of Laptev Sea were examined to investigate the environmental effects of polar rivers. PURE and LRE exhibited distinct environmental characteristics: low temperature and high salinity for PURE, and high temperature and low salinity for LRE, influenced by runoff size. Salinity more closely influenced microbial communities in LRE, with freshwater species playing a significant role in community composition. The findings revealed differences between two estuaries in community composition and diversity. Prokaryotes and microeukaryotes had shown different assembly patterns in response to habitat changes caused by terrestrial freshwater input. Furthermore, compared with the PURE, the co-occurrence and inter-domain network of the LRE, which was more affected by terrestrial input, was more complex and stable. Functional gene prediction revealed a higher gene expression of methane metabolism in LRE than in PURE, particularly those related to methane oxidation, and this conclusion could help better explore the impact of global warming on the methane cycle in the Arctic Marginal Seas. This study explored the increased freshwater runoffs under the background of global warming dramatically affect Arctic microplankton communities from community structure, assembly and gene expression aspects.

Novel CRISPR/Cas9-mediated knockout of LIG4 increases efficiency of site-specific integration in Chinese hamster ovary cell line.

AIM: To investigate the impact of deficiency of LIG4 gene on site-specific integration in CHO cells. RESULTS: CHO cells are considered the most valuable mammalian cells in the manufacture of biological medicines, and genetic engineering of CHO cells can improve product yield and stability. The traditional method of inserting foreign genes by random integration (RI) requires multiple rounds of screening and selection, which may lead to location effects and gene silencing, making it difficult to obtain stable, high-yielding cell lines. Although site-specific integration (SSI) techniques may overcome the challenges with RI, its feasibility is limited by the very low efficiency of the technique. Recently, SSI efficiency has been enhanced in other mammalian cell types by inhibiting DNA ligase IV (Lig4) activity, which is indispensable in DNA double-strand break repair by NHEJ. However, this approach has not been evaluated in CHO cells. In this study, the LIG4 gene was knocked out of CHO cells using CRISPR/Cas9-mediated genome editing. Efficiency of gene targeting in LIG4-/--CHO cell lines was estimated by a green fluorescence protein promoterless reporter system. Notably, the RI efficiency, most likely mediated by NHEJ in CHO, was inhibited by LIG4 knockout, whereas SSI efficiency strongly increased 9.2-fold under the precise control of the promoter in the ROSA26 site in LIG4-/--CHO cells. Moreover, deletion of LIG4 had no obvious side effects on CHO cell proliferation. CONCLUSIONS: Deficiency of LIG4 represents a feasible strategy to improve SSI efficiency and suggests it can be applied to develop and engineer CHO cell lines in the future.

Heterogeneous iron-nickel compound/RGO composites with tunable microwave absorption frequency and ultralow filler loading.

We fabricated heterogeneous iron-nickel compound/reduced graphene oxide (RGO) composites to obtain lightweight and high-efficiency microwave absorption materials with tunable absorption frequency. Using a facile hydrothermal route in combination with calcination at varying temperatures of 500-700 °C, the magnetic components Fe0.64Ni0.36, Fe0.64Ni0.36@Fe2Ni2N, and Fe2Ni2N were obtained. Due to strong interfacial polarization and dipole polarization as well as the conductive network formed by the substantial number of interfaces, all the magnetic RGO hybrids presented remarkable electromagnetic wave attenuation ability even when the filler content was only 5.2 wt%. More importantly, the optimization of reflection loss and tunable absorption frequency could be successfully realized by tuning the hybrid architecture and electromagnetic properties. This work reveals the mechanism of polarization-related dielectric relaxation of RGO, which provides new opportunities for designing lightweight and highly efficient microwave-absorbing materials by fully utilizing the hetero-interfacial effects.

[Effects of different fertilization patterns on soil improvement and vegetation restoration of desertified grassland in northwest Liaoning Province, China]. / 不同培肥模式对辽西北沙化草地土壤改良与植被恢复的影响.

Improving soil fertility is one of the key approaches for ecological restoration of the wind-sand area in northwest Liaoning Province. Taking wind-sand area in northwest Liaoning Province as test object, we conducted a fertilization experiment with treatments of inorganic fertilizer (nitrogen, phosphorus and potassium fertilizers), organic fertilizer, combined application of organic and inorganic fertilizers, and organic fertilizer combined with a biologically organic matrix (γ-polyglutamic acid), and no fertilizer as control. We measured soil organic matter content and extractable cations concentrations, vegetation coverage, and biomass under different fertilization treatments and determine the suitable fertilization mode. The results showed that compared to the control, inorganic fertilizer rapidly increased vegetation coverage and biomass, but high levels of inorganic fertilizer (150 kg N·hm-2) led to soil acidification and Ca2+ leaching. Organic fertilizer increased soil organic matter content, exchangeable K+, Ca2+, and Mg2+ contents, as well as coverage and biomass vegetation, especially combined with γ-polyglutamic acid. Overall, the combination of low levels of inorganic fertilizer (50 kg N·hm-2) and moderate levels of organic fertilizer (30000 kg·hm-2) was the best fertilization practice for the rapid and stable restoration of grassland in wind-sand area. Moreover, the extra addition of γ-polyglutamic acid (60 kg·hm-2)could effectively improve soil fertility.

Mechanisms of the novel pesticide sodium dodecyl benzene sulfonate in the mitigation of protozoan ciliated pathogens during microalgal cultivation.

Protozoan ciliates represent a common biological contaminant during microalgae cultivation, which will lead to a decline in microalgae productivity. This study investigated the effectiveness of sodium dodecyl benzene sulfonate (SDBS) in controlling ciliate populations within microalgae cultures. SDBS concentrations of 160 mg/L and 100 mg/L were found to effectively manage the representative species of ciliates contamination by Euplotes vannus and Uronema marinum during the cultivation of Synechococcus and Chlorella, and the growth vitality of microalgae has been restored. Additionally, SDBS at these concentrations reduced oxidative stress resistance and induced membrane damage to remove biological pollutants by modulating enzyme activity, affecting lipid, energy, amino acid metabolism pathways, and processes such as translation and protein folding. This research provides insights into the mechanisms through which SDBS effectively combats protozoan ciliates during the microalgal cultivation. This contributes to reduce biological pollution, ensure the overall productivity and healthy and sustainable management of microalgae ecosystems.

Development of novel monoclonal antibodies for blocking NF-κB activation induced by CD2v protein in African swine fever virus.

Background: CD2v, a critical outer envelope glycoprotein of the African swine fever virus (ASFV), plays a central role in the hemadsorption phenomenon during ASFV infection and is recognized as an essential immunoprotective protein. Monoclonal antibodies (mAbs) targeting CD2v have demonstrated promise in both diagnosing and combating African swine fever (ASF). The objective of this study was to develop specific monoclonal antibodies against CD2v. Methods: In this investigation, Recombinant CD2v was expressed in eukaryotic cells, and murine mAbs were generated through meticulous screening and hybridoma cloning. Various techniques, including indirect enzyme-linked immunosorbent assay (ELISA), western blotting, immunofluorescence assay (IFA), and bio-layer interferometry (BLI), were employed to characterize the mAbs. Epitope mapping was conducted using truncation mutants and epitope peptide mapping. Results: An optimal antibody pair for a highly sensitive sandwich ELISA was identified, and the antigenic structures recognized by the mAbs were elucidated. Two linear epitopes highly conserved in ASFV genotype II strains, particularly in Chinese endemic strains, were identified, along with a unique glycosylated epitope. Three mAbs, 2B25, 3G25, and 8G1, effectively blocked CD2v-induced NF-κB activation. Conclusions: This study provides valuable insights into the antigenic structure of ASFV CD2v. The mAbs obtained in this study hold great potential for use in the development of ASF diagnostic strategies, and the identified epitopes may contribute to vaccine development against ASFV.

Rational Design of Triazinone Derivatives with Low Bee Toxicity Based on the Binding Mechanism of Neonicotinoids to Apis mellifera.

Bees, one of the most vital pollinators in the ecosystem and agriculture, are currently threatened by neonicotinoids. To explore the molecular mechanisms of neonicotinoid toxicity to bees, the different binding modes of imidacloprid, thiacloprid, and flupyradifurone with nicotinic acetylcholine receptor (nAChR) α1ß1 and cytochrome P450 9Q3 (CYP9Q3) were studied using homology modeling and molecular dynamics simulations. These mechanisms provided a basis for the design of compounds with a potential low bee toxicity. Consequently, we designed and synthesized a series of triazinone derivatives and assessed their bioassays. Among them, compound 5a not only displayed substantially insecticidal activities against Aphis glycines (LC50 = 4.40 mg/L) and Myzus persicae (LC50 = 6.44 mg/L) but also had low toxicity to Apis mellifera. Two-electrode voltage clamp recordings further confirmed that compound 5a interacted with the M. persicae nAChR α1 subunit but not with the A. mellifera nAChR α1 subunit. This work provides a paradigm for applying molecular toxic mechanisms to the design of compounds with low bee toxicity, thereby aiding the future rational design of eco-friendly nicotinic insecticides.

Dual-Specificity Inhibitor Targets Enzymes of the Trehalose Biosynthesis Pathway.

To reduce the risk of resistance development, a novel fungicide with dual specificity is demanded. Trehalose is absent in animals, and its synthases, trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP), are safe fungicide targets. Here, we report the discovery of a dual-specificity inhibitor of MoTps1 (Magnaporthe oryzae Tps1, TPS) and MoTps2 (M. oryzae Tps2, TPP). The inhibitor, named A1-4, was obtained from a virtual screening and subsequent surface plasmon resonance screening. In in vitro assays, A1-4 interacts with MoTps1 and MoTps2-TPP (MoTps2 TPP domain) and inhibits their enzyme activities. In biological activity assays, A1-4 not only inhibits the virulence of M. oryzae on host but also causes aggregation of conidia cytosol, which is a characteristic phenotype of MoTps2. Furthermore, hydrogen/deuterium exchange mass spectrometry assays support the notion that A1-4 binds to the substrate pockets of TPS and TPP. Collectively, A1-4 is a promising hit compound for the development of safe fungicide with dual-target specificity.

Spatial distribution, ecological risk and health risk assessment of heavy metals in agricultural soil from Ankang basin, Shaanxi Province.

In order to assess the heavy metal pollution features, ecological dangers, and health risk status posed to human beings by soils in the Ankang Basin, a study was conducted. This involved the collection of 38 surface soil samples, followed by the determination of elemental levels of arsenic, mercury, copper, cadmium, lead, chromium, nickel, and zinc. The concentrations of arsenic, mercury, copper, cadmium, lead, chromium, nickel, and zinc were quantified through the collection of 38 surface soil samples. The data obtained from the study was subjected to analysis and evaluation utilizing various academic methodologies, including the geo-accumulation index method, potential ecological risk assessment method, human health risk assessment model, and Monte Carlo simulation method. The findings indicated that the concentrations of the eight heavy metals in the soil above the background levels, with only Cadmium (Cd) marginally surpassing the threshold set for controlling soil pollution risks. The ground accumulation index revealed a higher degree of soil pollution with mercury, cadmium, copper, and zinc components. According to the possible ecological risk index, the presence of mercury and cadmium elements poses significant ecological hazards. The geographical distribution analysis suggests that these risks mostly stem from the combined impacts of human activities and the topographical and geomorphological characteristics of the river valley. The findings of the human health risk assessment indicated that the non-carcinogenic risk fell within acceptable limits. Additionally, it was observed that the carcinogenic risk associated with arsenic, mercury, cadmium, and nickel was comparatively greater for children as compared to adults. The results of the Monte Carlo simulations indicate that the non-carcinogenic hazards have a negligible effect on human health. However, it was seen that arsenic and nickel have a greater likelihood of presenting a substantial carcinogenic risk to humans, particularly in relation to the pediatric population, hence exerting a more pronounced impact on their health. In general, it is observed that conventional deterministic risk assessments tend to overstate the potential health risks associated with a given situation. Conversely, the utilization of Monte Carlo simulations has been found to effectively mitigate uncertainties in health risk assessments. It has been observed that children exhibit a higher vulnerability to both carcinogenic and non-carcinogenic health impacts resulting from exposure to heavy metals present in soil, in comparison to adults. It is recommended that residents prioritize the surveillance of soil heavy metals in relation to potential impacts on human health.

Discovery of novel isopropanolamine inhibitors against MoTPS1 as potential fungicides with unique mechanisms.

The resistance and ecotoxicity of fungicides seriously restrict our ability to effectively control Magnaporthe oryzae. Discovering fungicidal agents based on novel targets, including MoTPS1, could efficiently address this situation. Here, we identified a hit VS-10 containing an isopropanolamine fragment as a novel MoTPS1 inhibitor through virtual screening, and forty-four analogs were synthesized by optimizing the structure of VS-10. Utilizing our newly established ion-pair chromatography (IPC) and leaf inoculation methods, we found that compared to VS-10, its analog j11 exhibited substantially greater inhibitory activity against both MoTPS1 and the pathogenicity of M. oryzae. Molecular simulations clarified that the electrostatic interactions between the bridging moiety of isopropanolamine and residue Glu396 of contributed significantly to the binding of j11 and MoTPS1. We preliminarily revealed the unique fungicidal mechanism of j11, which mainly impeded the infection of M. oryzae by decreasing sporulation, killing a small portion of conidia and interfering with the accumulation of turgor pressure in appressoria. Thus, in this study, a novel fungicide candidate with a unique mechanism targeting MoTPS1 was screened and discovered.

Potential inhibitory effects of compounds ZK-PI-5 and ZK-PI-9 on trehalose and chitin metabolism in Spodoptera frugiperda (J. E. Smith).

Introduction: Spodoptera frugiperda is an omnivorous agricultural pest which is great dangerous for grain output. Methods: In order to investigate the effects of potential trehalase inhibitors, ZK-PI-5 and ZK-PI-9, on the growth and development of S. frugiperda, and to identify new avenues for S. frugiperda control, we measured the content of the trehalose, glucose, glycogen and chitin, enzyme activity, and gene expression levels in trehalose and chitin metabolism of S. frugiperda. Besides, their growth and development were also observed. Results: The results showed that ZK-PI-9 significantly reduced trehalase activity and ZK-PI-5 significantly reduced membraned-bound trehalase activity. Moreover, ZK-PI-5 inhibited the expression of SfTRE2, SfCHS2, and SfCHT, thus affecting the chitin metabolism. In addition, the mortality of S. frugiperda in pupal stage and eclosion stage increased significantly after treatment with ZK-PI-5 and ZK-PI-9, which affected their development stage and caused death phenotype (abnormal pupation and difficulty in breaking pupa). Discussion: These results have provided a theoretical basis for the application of trehalase inhibitors in the control of agricultural pests to promote future global grain yield.

A retrospective study on the physical growth of twins in the first year after birth.

Objectives: This study analyzed the physical growth of small for gestational age (SGA) and appropriate for gestational age (AGA) twins up to one year after birth. Methods: Weight, length, and head circumference data of 0-1 year-old twins were collected from the Child Health Care System from 2010 to 2019. Physical data were presented as Z-scores. Five parameters - growth level of weight, body length, head circumference, growth velocity, and body proportion (weight for length) were compared in twins. Results: A total of 3,909 cases were collected (22.61% SGA, 77.39% AGA). 1. In both groups, WAZ (Weight for age z-score), HCZ (Head circumference for age z-score), and LAZ (Length for age z-score) increased more rapidly in the first 6 months. By one year of age, WAZ, HCZ, and LAZ had reached the normal range, but none had reached the average level of normal singleton children. 2. The mean values of WAZ, HCZ, and LAZ in the AGA group were between -1 and 0, and between -2 and - 1 in the SGA group, in the first year after birth. The SGA group lagged significantly behind the AGA group. The LAZ score of SGA and AGA was lower than the WAZ and HCZ scores. 3. The proportion of preterm AGA was the largest in twins, and the growth rate of preterm AGA was the fastest. Preterm twins had greater growth potential than term twins. However, the growth level of preterm SGA was always low. 4. The WFLZ (Weight for length z-score) in each group was approximately close to 0. The WFLZ of SGA was smaller than that of AGA twins at most time points. After 4 months of age, the WFLZ of twins had a downward trend. The WFLZ of preterm SGA approached -1 at approximately 1 year old. Conclusion: The physical growth of SGA and AGA in twins in the first year can reach the normal range but cannot reach the average level of normal singleton children. More attention should be paid to SGA in twins, especially preterm SGA. We should give proper nutritional guidance after 4 months of age to ensure the appropriate body proportion (weight for length) of SGA in twins. Clinical trial registration: www.chictr.org.cn, CTR2000034761.

Computer tomography-guided negative pressure drainage treatment of intrathoracic esophagojejunal anastomotic leakage: A case report.

BACKGROUND: Esophagojejunal anastomotic leakage (EJAL) is a serious and potentially crucial complication of total gastrectomy and represents the major cause of postoperative death, with a mortality rate of up to 50%. However, treatment remains challenging and controversial. We report here the case of a patient whose intrathoracic EJAL was successfully treated with computer tomography (CT)-guided negative pressure drainage treatment. CASE SUMMARY: A 69-year-old male patient complained of difficulty swallowing within the last six months. He was diagnosed with esophagogastric junction carcinoma, Siewert II, cT3N0M0 stage II. Total gastrectomy and Roux-en-Y esophagojejunostomy were performed. High fever, left chest pain and dyspnea appeared on postoperative day 5, and EJAL was confirmed by CT, gastroscopy and oral blue-dimethylene tests. Conservative treatment measures were applied immediately, including antibiotics, nasojejunal tubes, and repeated thoracic puncture and drainage under ultrasound guidance. However, without sufficient and effective drainage, the thoracic infection and systemic condition continued to deteriorate. With the cooperation of multiple departments, percutaneous CT-guided drainage (24 Fr 7 mm) in the thoracic cavity was successfully placed near the anastomotic leakage. Because of continuous negative pressure suction, the infection symptoms were effectively controlled and the general situation gradually recovered. Subsequent follow-up examination showed that the patient was in good condition. CONCLUSION: Negative pressure drainage via CT may represent an effective minimally invasive approach to treating intrathoracic EJAL.

Case report: Conversion therapy for advanced intrahepatic cholangiocarcinoma using PD-1 inhibitor plus S-1 and nab-paclitaxel.

Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant hepatobiliary tumor with a high rate of advanced disease at initial presentation. Conversion into resectable iCCA is important for improving the prognosis. Immunotherapy-based regimens are being increasingly used for treating advanced iCCA in recent years. However, the use of combined chemotherapy and immunotherapy for conversion has rarely been reported. The aim of this report was to present the outcomes of a 52-year-old female patient with IIIB iCCA. The patient was treated with a programmed cell death protein-1 inhibitor plus S-1 and nab-paclitaxel. The postoperative histopathological results indicated pathologic complete response after six cycles of systematic treatment. The patient is currently disease-free for one year.

Rational Design and Identification of Novel Piperine Derivatives as Multichitinase Inhibitors.

Asian corn borer (Ostrinia furnacalis) is one of the most destructive pests in agriculture. Three chitinases OfChtI, OfChtII, and OfChi-h are regarded as potential targets for discovering novel agrochemicals to control O. furnacalis. In this study, piperine (Ki = 43.78∼83.03 µM) was first shown to exhibit inhibitory activities against all three chitinases. Subsequently, 19 novel piperine derivatives were rationally designed based on the conserved aromatic residues of three chitinases and then synthesized. Among them, Compound 5k (Ki = 11.78∼22.82 µM) was identified as the most effective multichitinase inhibitor and indeed displayed higher insecticidal activity against O. furnacalis than dual- or single-chitinase inhibitors. Molecular mechanism studies clarified that Compound 5k interacted with two conserved TRP and TYR of three chitinases in identical modes through hydrogen bonds, hydrophobic, and π-π interactions. Moreover, the microinjection experiment indicated that Compound 5k exhibited substantial sublethal effects against O. furnacalis by regulating its growth and development. This study provides evidence of multichitinase inhibitors to be applied in the control of O. furnacalis.

NEUROD1 predicts better prognosis in pancreatic cancer revealed by a TILs-based prognostic signature.

It has been well-defined that tumor-infiltrating lymphocytes (TILs) play critical roles in pancreatic cancer (PaCa) progression. This research aimed to comprehensively explore the composition of TILs in PaCa and their potential clinical significance. A total of 178 samples from the TCGA and 63 samples from the GSE57495 dataset were enrolled in our study. ImmuCellAI was applied to calculate the infiltrating abundance of 24 immune cell types in PaCa and further survival analysis revealed the prognostic values of TILs in PaCa. Moreover, the Hallmark enticement analysis of differentially expressed genes (DEGs) between low- and high-risk groups was performed as well. Immunohistochemistry staining was used to evaluate NEUROD1 expression. As result, different kinds of TILs had distinct infiltrating features. In addition, Specific TILs subsets had notable prognostic values in PaCa. We further established a 6-TILs signature to assess the prognosis of PaCa patients. Kaplan-Meier and Cox regression analyses both suggested the significant prognostic value of the signature in PaCa. Based on the prognostic signature, we screened a great deal of potential prognostic biomarkers and successfully validated NEUROD1 as a novel prognostic biomarker in PaCa. Overall, the current study illuminated the immune cells infiltrating the landscape in PaCa and identified a TILs-dependent signature and NEUROD1 for prognostic prediction in PaCa patients.

Piperonyl-Tethered Rhodanine Derivatives Potently Inhibit Chitinolytic Enzymes of Ostrinia furnacalis.

Insect pest chitinases are potential target for developing new insect growth regulators. Piperine was found first to inhibit the insect chitinase (OfChi-h) from Ostrinia furnacalis (Asian corn borer) in this work, except for previously reported OfChtI. Novel piperonyl-tethered rhodanine derivatives 7a-j were rationally designed with piperine as lead and synthesized by introducing a unique rhodanine moiety into the piperine scaffold based on the similar binding cavity of OfChtI and OfChi-h. Compared to piperine, compounds 7a-j showed approximately 100- to 400-fold or 110- to 210-fold higher inhibitory capacity against two chitinases, respectively. Molecular mechanism studies indicated that π interactions are crucial for improving inhibitory activity against two chitinases due to the introduction of the conjugated rhodanine ring. Moreover, compounds 7a-c could dramatically inhibit the growth and development of O. furnacalis larvae by in vivo activity evaluation. This study provides novel piperonyl-tethered rhodanine derivatives inhibiting dual chitinases as insect growth regulator candidates.

Regressive Autism Spectrum Disorder: High Levels of Total Secreted Amyloid Precursor Protein and Secreted Amyloid Precursor Protein-α in Plasma.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social communication difficulties, repetitive behaviors, and parochial interests. Individuals with regressive ASD (RA), a unique subtype, have poor outcomes. Moreover, there are currently no validated blood-based biomarkers for ASD, hindering early diagnosis and treatment. This study was the first to examine plasma levels of total secreted amyloid precursor protein (sAPPtotal), secreted amyloid precursor protein-α (sAPPα), and secreted amyloid precursor protein-ß (sAPPß) in children diagnosed with RA (n = 23) and compare them with the levels in age-matched children with non-regressive ASD (NRA) (n = 23) and typically developing (TD) controls (n = 23). We found that sAPPtotal and sAPPα levels were significantly higher in children with RA than in children with NRA or in TD controls. In contrast, no difference was observed in sAPPß levels. In conclusion, increased plasma levels of sAPPtotal and sAPPα may be valuable biomarkers for the early identification of ASD regression. Prospective studies will be conducted using a larger sample to further investigate these differences.

Association between mitogen-activated protein kinase kinase kinase 1 rs889312 polymorphism and breast cancer risk: evidence from 59,977 subjects.

Published data on the association between mitogen-activated protein kinase kinase kinase 1 (MAP3K1) gene rs889312 polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of seven eligible articles including 26,015 cases and 33,962 controls based on the search criteria were involved in this meta-analysis. We observed that the MAP3K1 rs889312 polymorphism was significantly correlated with breast cancer risk from the fixed effects model when all studies were pooled into the meta-analysis (the allele contrast model: OR 1.09, 95% CI 1.07-1.12; the homozygote codominant: OR 1.22, 95% CI 1.15-1.29; the heterozygote codominant: OR 1.07, 95% CI 1.04-1.11; the dominant model: OR 1.10, 95% CI 1.06-1.13; the recessive model: OR 1.18, 95% CI 1.12-1.25). No significant association was found in the BRCA1 mutation carriers in all genetic models. When stratified by BRCA2 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (C vs. A: OR 1.12, 95% CI 1.01-1.23; CC vs. AA: OR 1.35, 95% CI 1.06-1.71; the recessive model: OR 1.31, 95% CI 1.05-1.65). There was no evidence for significant association between MAP3K1 rs889312 polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort for all comparison models. In conclusion, this meta-analysis suggests that the MAP3K1 rs889312 C allele is a low-penetrant risk factor for developing breast cancer, and there is limited evidence to indicate that MAP3K1 rs889312 polymorphism is associated with increased risk of breast cancer in BRCA1 mutation carriers.