PPP2CA Inhibition Promotes Ferroptosis Sensitivity Through AMPK/SCD1 Pathway in Colorectal Cancer.

PURPOSE: Colorectal cancer (CRC) is a very common malignancy of the digestive system. Despite a variety of treatments including surgery, chemotherapeutic and targeted drugs, the prognosis for patients with CRC is still unsatisfactory and the mortality remains high. Protein phosphorylation plays an essential role in tumorigenesis and progression and is also crucial for protein to act with proper functions. Ferroptosis is found widely involved in various diseases especially tumors as a newly identified programmed cell death. METHODS: In our study, we aimed at PPP2CA as a prospective target which may play a crucial role in CRC progression. In one hand, knockdown of PPP2CA significantly enhanced the malignant phenotype in HCT116. In the other hand, knockdown of PPP2CA significantly enhanced Erastin-induced ferroptosis as well. RESULTS: Specifically, knockdown of PPP2CA in HCT116 significantly increased the relative level of malondialdehyde (MDA), reactive oxygen species (ROS) and Fe2+, and decreased GSH/GSSG ratio after the treatment of certain concentration of Erastin. Besides, we found that the inhibition of PPP2CA further led to the suppression of SCD1 expression in CRC cells in a AMPK-dependent way. CONCLUSION: Ultimately, we conclude that PPP2CA may regulate Erastin-induced ferroptosis through AMPK/SCD1 signaling pathway.

Effect of microbial inoculum on composting efficiency in the composting process of spent mushroom substrate and chicken manure.

This work aimed to investigate the microbial mechanisms for the improvement of composting efficiency driven by the compound microbial inoculum (MI) (Bacillus subtilis SL-44, Enterobacter hormaechei Rs-189 and Trichoderma reesei) during co-composting of spent mushroom substrate (SMS) and chicken manure (CM). The treatments used in the study were as follows: 1) MI (inoculation with microbial inoculum), 2) CI (inoculation with commercial microbial inoculum), and 3) CK (without inoculation). The results demonstrated that MI increased the seed germination index (GI) by 25.11%, and contents of humus, humic acid (HA) and available phosphorus (AP) were correspondingly promoted by 12.47%, 25.93% and 37.16%, respectively. The inoculation of MI increased the temperature of the thermophilic stage by 3-7 °C and achieved a cellulose degradation rate of 52.87%. 16S rRNA gene analysis indicated that Actinobacteria (11.73-61.61%), Firmicutes (9.46-65.07%), Proteobacteria (2.86-32.17%) and Chloroflexi (0.51-10.92%) were the four major phyla during the inoculation composting. Bacterial metabolic functional analysis revealed that pathways involved in amino acid and glycan biosynthesis and metabolism were boosted in the thermophilic phase. There was a positive correlation between bacterial communities and temperature, humification and phosphorus fractions. The average dry weight, fresh weight and seedling root length in the seedling substrates adding MI compost were 1.13, 1.23 and 1.06 times higher than those of the CK, respectively. This study revealed that biological inoculation could improve the composting quality and efficiency, potentially benefiting the resource utilization of agricultural waste resources.

An Experimental Study on Combustion and Cycle-by-Cycle Variations of an N-Butanol Engine with Hydrogen Direct Injection under Lean Burn Conditions.

This study experimentally investigated the effects of hydrogen direct injection on combustion and the cycle-by-cycle variations in a spark ignition n-butanol engine under lean burn conditions. For this purpose, a spark ignition engine installed with a hydrogen and n-butanol dual fuel injection system was specially developed. Experiments were conducted at four excess air ratios, four hydrogen fractions(φ(𝐻2)) and pure n-butanol. Engine speed and intake manifold absolute pressure (MAP) were kept at 1500 r/min and 43 kPa, respectively. The results indicate that the θ0-10 and θ10-90 decreased gradually with the increase in hydrogen fraction. Additionally, the indicated mean effective pressure (IMEP), the peak cylinder pressure (Pmax) and the maximum rate of pressure rise ((dP/dφ)max) increased gradually, while their cycle-by-cycle variations decreased with the increase in hydrogen fraction. In addition, the correlation between the (dP/dφ)max and its corresponding crank angle became weak with the increase in the excess air coefficient (λ), which tends to be strongly correlated with the increase in hydrogen fraction. The coefficient of variation of the Pmax and the IMEP increased with the increase in λ, while they decreased obviously after blending in the hydrogen under lean burn conditions. Furthermore, when λ was 1.0, a 5% hydrogen fraction improved the cycle-by-cycle variations most significantly. While a larger hydrogen fraction is needed to achieve the excellent combustion characteristics under lean burn conditions, hydrogen direct injection can promote combustion process and is beneficial for enhancing stable combustion and reducing the cycle-by-cycle variations.

A risk model and nomogram for high-frequency hearing loss in noise-exposed workers.

BACKGROUND: High-frequency hearing loss is a significant occupational health concern in many countries, and early identification can be effective for preventing hearing loss. The study aims to construct and validate a risk model for HFHL, and develop a nomogram for predicting the individual risk in noise-exposed workers. METHODS: The current research used archival data from the National Key Occupational Diseases Survey-Sichuan conducted in China from 2014 to 2017. A total of 32,121 noise-exposed workers completed the survey, of whom 80% workers (n = 25,732) comprised the training cohort for risk model development and 20% workers (n = 6389) constituted the validation cohort for model validation. The risk model and nomogram were constructed using binary logistic models. The effectiveness and calibration of the model were evaluated with the receiver operating characteristic curve and calibration plots, respectively. RESULTS: A total of 10.06% of noise-exposed workers had HFHL. Age (OR = 1.09, 95% CI: 1.083-1.104), male sex (OR = 3.25, 95% CI: 2.85-3.702), noise exposure duration (NED) (OR = 1.15, 95% CI: 1.093-1.201), and a history of working in manufacturing (OR = 1.50, 95% CI: 1.314-1.713), construction (OR = 2.29, 95% CI: 1.531-3.421), mining (OR = 2.63, 95% CI: 2.238-3.081), or for a private-owned enterprise (POE) (OR = 1.33, 95% CI: 1.202-1.476) were associated with an increased risk of HFHL (P < 0.05). CONCLUSIONS: The risk model and nomogram for HFHL can be used in application-oriented research on the prevention and management of HFHL in workplaces with high levels of noise exposure.

Long non-coding RNA H19 suppresses retinoblastoma progression via counteracting miR-17-92 cluster.

Long non-coding RNAs (lncRNAs) are frequently dysregulated and play important roles in many cancers. lncRNA H19 is one of the earliest discovered lncRNAs which has diverse roles in different cancers. However, the expression, roles, and action mechanisms of H19 in retinoblastoma are still largely unknown. In this study, we found that H19 is downregulated in retinoblastoma tissues and cell lines. Gain-of-function and loss-of-function assays showed that H19 inhibits retinoblastoma cell proliferation, induces retinoblastoma cell cycle arrest and cell apoptosis. Mechanistically, we identified seven miR-17-92 cluster binding sites on H19, and found that H19 directly bound to miR-17-92 cluster via these seven binding sites. Through binding to miR-17-92 cluster, H19 relieves the suppressing roles of miR-17-92 cluster on p21. Furthermore, H19 represses STAT3 activation induced by miR-17-92 cluster. Hence, our results revealed that H19 upregulates p21 expression, inhibits STAT3 phosphorylation, and downregulates the expression of STAT3 target genes BCL2, BCL2L1, and BIRC5. In addition, functional assays demonstrated that the mutation of miR-17-92 cluster binding sites on H19 abolished the proliferation inhibiting, cell cycle arrest and cell apoptosis inducing roles of H19 in retinoblastoma. In conclusion, our data suggested that H19 inhibits retinoblastoma progression via counteracting the roles of miR-17-92 cluster, and implied that enhancing the action of H19 may be a promising therapeutic strategy for retinoblastoma.

Long noncoding RNA BDNF-AS is a potential biomarker and regulates cancer development in human retinoblastoma.

BACKGROUND: Long non-coding RNAs (lncRNA) have been shown to play important roles in human cancer. We examined expression, prognostic potential and functional roles of lncRNA, brain-derived neurotrophic factor antisense (BDNF-AS) in human retinoblastoma (RB). METHODS: BDNF-AS expression in RB tumors was characterized according to the clinicopathological parameters of patients. BDNF-AS mRNA level was compared between RB tumors and normal retinas, as well as RB cell lines and normal retinal epithelial cells. RB patients' overall survival was compared between those with low and high BDNF-AS tumor expressions. Statistical analysis was performed to examine the independence of BDNF-AS being cancer biomarker in RB. In Y79 and WERI-Rb-1 cells, BDNF-AS was upregulated. It's effect on cancer proliferation, migration and cell-cycle transition were assessed. RESULTS: BDNF-AS is downregulated in RB tumors and cell lines. Low BDNF-AS expression in RB tumors is correlated with patients' advanced clinical stage and tumor differentiation status. Low BDNF-AS expression is associated with shorter overall survival and may be acting as an independent marker in RB. In Y79 and WERI-Rb-1 cells, forced overexpression of BDNF-AS inhibited cancer proliferation and migration. It also induced cell-cycle arrest at G0/G1 phase by downregulating CDC42, Cyclin E and BDNF. CONCLUSION: BDNF-AS is lowly expressed, and may be used as a prognostic biomarker in RB. Upregulating BDNF-AS has inhibitory effect on RB development, probably through the suppression of cell-cycle transition.

[Research on Spectrum Matching Method for PbSe Quantum Dots Luminescence Spectrum and Gas Absorption Spectrum].

As typical nano metarials in near infrared waveband, PbSe Quantum Dots have a very large exciton Bohr radius of 46 nm and a small band gap of 0.28 eV at room temperature. PbSe QDs have very unique properties, such as the quantum confined optical property, and which possess high photoluminescence (PL) quantum yield (QY) with size dependent tunable wavelength emissions. By analyzing the luminescence spectrum of PbSe Quantum Dots, a method through adjusting the particle size of PbSe Quantum Dots (QDs) to match gas absorption spectrum was presented in this paper. 4.6 and 6.1 nm PbSe QDs were synthesized and deposited on the GaN chip to fabricate the NIR QDs light sources. The PbSe QDs-UV glue composites thickness was determined to be 48.0 and 671.5 µm for 6.1 and 4.6 nm PbSe QDs. The NIR QDs were used to detect the C2H2 and NH3 gas. The experiments show that the PL spectrum of 4.6 nm NIR QDs can cover the entire absorption spectrum of C2H2 gas (from 1 500 to 1 550 nm) and the PL spectrum of 6.1 nm NIR QDs can cover the entire absorption spectrum of NH3 gas (from 1 900 to 2 060 nm). By changing the quantum size of QDs, the PL peak of the NIR QDS light source can be adjusted to cover the absorption peak of different gases. The matching method presented in this paper is efficient and feasible, which has great application potential in gas detection.

Effect of Crude Protein Levels in Concentrate and Concentrate Levels in Diet on In vitro Fermentation.

The effect of concentrate mixtures with crude protein (CP) levels 10%, 13%, 16%, and 19% and diets with roughage to concentrate ratios 80:20, 60:40, 40:60, and 20:80 (w/w) were determined on dry matter (DM) and organic matter (OM) digestibility, and fermentation metabolites using an in vitro fermentation technique. In vitro fermented attributes were measured after 4, 24, and 48 h of incubation respectively. The digestibility of DM and OM, and total volatile fatty acid (VFA) increased whereas pH decreased with the increased amount of concentrate in the diet (p<0.001), however CP levels of concentrate did not have any influence on these attributes. Gas production reduced with increased CP levels, while it increased with increasing concentrate levels. Ammonia nitrogen (NH3-N) concentration and microbial CP production increased significantly (p<0.05) by increasing CP levels and with increasing concentrate levels in diet as well, however, no significant difference was found between 16% and 19% CP levels. Therefore, 16% CP in concentrate and increasing proportion of concentrate up to 80% in diet all had improved digestibility of DM and organic matter, and higher microbial protein production, with improved fermentation characteristics.

Impact of next-generation sequencing on antimicrobial treatment in immunocompromised adults with suspected infections.

BACKGROUND: Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment. The objective of the study was to assess the diagnostic value of next-generation sequencing (NGS) for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections. METHODS: This was a retrospective study. Between January and August 2020, 47 adult immunocompromised patients underwent NGS testing under the following clinical conditions: 1) prolonged fever and negative conventional cultures; 2) new-onset fever despite empiric antimicrobial treatment; and 3) afebrile with suspected infections on imaging. Clinical data, including conventional microbial test results and antimicrobial treatment before and after NGS, were collected. Data were analyzed according to documented changes in antimicrobial treatment (escalated, no change, or de-escalated) after the NGS results. RESULTS: The median time from hospitalization to NGS sampling was 19 d. Clinically relevant pathogens were detected via NGS in 61.7% of patients (29/47), more than half of whom suffered from fungemia (n=17), resulting in an antimicrobial escalation in 53.2% of patients (25/47) and antimicrobial de-escalation in 0.2% of patients (1/47). Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella, Pneumocystis jirovecii, and Candida. In the remaining three cases, NGS detected clinically relevant pathogens also detected by conventional cultures a few days later. The antimicrobial treatment was subsequently adjusted according to the susceptibility test results. Overall, NGS changed antimicrobial management in 55.3% (26/47) of patientst, and conventional culture detected clinically relevant pathogens in only 14.9% of patients (7/47). CONCLUSION: With its rapid identification and high sensitivity, NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.

MiR199b suppresses expression of hypoxia-inducible factor 1α (HIF-1α) in prostate cancer cells.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that post-transcriptionally repress expression of target genes via imperfect base-pairing with the 3'-untranslated region (3'-UTR). The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays important roles in physiology and pathology. Constitutive over-expression of HIF-1α is observed in many types of cancers including prostate carcinoma, but the mechanisms underlying this event remain largely unknown. Here we investigated the expression of miR199b and HIF-1α in normal prostate tissue, prostate cancer tissues and prostate carcinoma (PCa) cell lines LNCaP, PC-3 and DU145.We found that miR-199b expression level was decreased in prostate cancer while HIF-1α was significantly over-expressed. Furthermore, we postulated the posttranscriptional regulation of HIF-1α by miR199b through bioinformatics analysis, and herein we experimentally demonstrated that miR199b negatively regulated HIF-1α by targeting its 3'-untranslated region. Artificial over-expression of miR199b by using adenoviral vectors in prostate cancer PC-3 and DU145 cells significantly down-regulated HIF-1α, together with reduced cell growth and increased cell death.

[The expression and function of anti-apoptotic Bfl-1 in prostate cancer].

OBJECTIVE: To determine the expression of Bcl2 related protein A1(Bfl-1) mRNA in prostate cancer cell lines and tissues, and to explore the functions of Bfl-1 in prostate adenocarcinoma. METHODS: RT-PCR, real-time quantitative PCR (Q-PCR)and in situ hybridization (ISH) were used to detect the expression of Bfl-1 mRNA in prostate cancer cell lines, tissues and benign prostate hyperplasia (BPH) tissue samples. The relationship between Bfl-1 expression and clinicopathological parameters was analyzed. Antisense oligonucleotides (ASONs) were used to interfere the expression of Bfl-1 and its effects on prostate cancer cells. MTT was used to detect the survival, morphologic changes of prostate cancer cells was observed by inverted microscope. RESULTS: Bfl-1 mRNA, detected by RT-PCR, Q-PCR and ISH, was overexpressed in the androgen-independent prostate cancer cell lines PC-3 and DU145, but not detectable in the androgen-dependent prostate cancer cell line LNCaP and BPH tissue samples (P < 0.05). Significantly higher Bfl-1 mRNA levels were observed in higher stage and metastatic prostate cancer cases than those without metastasis or of low stage. ASONs targeting Bfl-1 significantly inhibited androgen-independent prostate cancer cell growth (P < 0.05), cell was rounding off or fragmentation. CONCLUSION: Bfl-1 is involved in maintaining the hormone-independent prostate cancer cell growth. Bfl-1 may become a new therapeutic target in advanced prostate cancer.

Quantitative assessment of OCT and OCTA parameters in diabetic retinopathy with and without macular edema: single-center cross-sectional analysis.

Aim: The retinal and choroidal parameters were analyzed to understand the impairment of microcirculation of both retina and choroid in patients with diabetic retinopathy (DR). Methods: Fifty-five treatment-naive non-proliferative diabetic retinopathy (NPDR) patients (75 eyes) with type 2 diabetes mellitus (T2DM), including 28 patients (36 eyes) with diabetic macular edema (DME) and 27 patients (39 eyes) without DME, and 25 healthy subjects (47 eyes) were enrolled in this study. The following parameters of DR patients with and without DME were evaluated: the foveal avascular zone area (FAZ-a), FAZ perimeter (FAZ-p), FAZ circularity index (FAZ-CI), total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow area percentage, superficial capillary plexus (SCP), and deep capillary plexus (DCP). Results: SCP, DCP, and the percentage of choriocapillaris flow area were significantly different between DR patients with and without DME. The DR patients presented lower LA, CVI, and FAZ-CI compared to those of healthy controls (all p < 0.05). The percentage of choriocapillaris flow area in DR patients with and without DME was significantly lower than that in healthy controls (p < 0.05). SCP and DCP were significantly correlated with FAZ-a and FAZ-p but presented insignificant associations with FAZ-CI. Conclusions: Optical coherence tomography (OCT) and OCT angiography (OCTA) parameters, such as LA, CVI, FAZ-CI, and the percentage of choriocapillaris flow area, were reduced compared to those in controls, indicating that the microcirculations of the retina and choroid in the macular area were impaired in DR patients with DME and without DME.

In situ resource utilization of lunar soil for highly efficient extraterrestrial fuel and oxygen supply.

Building up a lunar settlement is the ultimate aim of lunar exploitation. Yet, limited fuel and oxygen supplies restrict human survival on the Moon. Herein, we demonstrate the in situ resource utilization of lunar soil for extraterrestrial fuel and oxygen production, which may power up our solely natural satellite and supply respiratory gas. Specifically, the lunar soil is loaded with Cu species and employed for electrocatalytic CO2 conversion, demonstrating significant production of methane. In addition, the selected component in lunar soil (i.e. MgSiO3) loaded with Cu can reach a CH4 Faradaic efficiency of 72.05% with a CH4 production rate of 0.8 mL/min at 600 mA/cm2. Simultaneously, an O2 production rate of 2.3 mL/min can be achieved. Furthermore, we demonstrate that our developed process starting from catalyst preparation to electrocatalytic CO2 conversion is so accessible that it can be operated in an unmmaned manner via a robotic system. Such a highly efficient extraterrestrial fuel and oxygen production system is expected to push forward the development of mankind's civilization toward an extraterrestrial settlement.

Job stress and burnout among ideological and political education teachers during the COVID-19 pandemic: A moderated mediation model.

Job burnout among ideological and political education (IPE) teachers in China is a complex problem and rewarding area of research. This study explored the relationship between job stress and burnout among ideological and political education (IPE) teachers in the context of the COVID-19 pandemic. The cross-sectional design included a sample of self-report measures sampled from 362 university IPE teachers. Using multiple line regression analysis, our main findings were as follows: first, job stress had a significant predictive effect on work-family conflict and job burnout; second, work-family conflict mediated the relationship between job stress and job burnout; and finally, resilience productively moderated the relationships between job stress and both work-family conflict and burnout. These results suggest that resilient IPE teachers are less likely to suffer from burnout. They indicate the need to systematically foster resilience in trainees and experienced instructors as a means of coping with adverse work conditions.

How Does Career Calling Influence Preservice Teachers' Learning Engagement? A Multiple Mediating Roles of Occupational Self-Efficacy and Vocational Outcome Expectation.

This study used social cognitive career theory (SCCT) to explore the relationships between career calling, occupational self-efficacy, vocational outcome expectation, and learning engagement among preservice teachers at a normal university in China. Data from 1,029 preservice teachers were analyzed using Structural Equation Modeling. The results revealed that career calling was found to be significantly and positively affected on learning engagement; occupational self-efficacy and vocational outcome expectation were identified as key mediators of this relationship. These findings advance our knowledge of how best to promote the learning engagement of preservice teachers and may inform the future design of teacher development programs.

Deep Learning Method for Grasping Novel Objects Using Dexterous Hands.

Robotic grasping ability lags far behind human skills and poses a significant challenge in the robotics research area. According to the grasping part of an object, humans can select the appropriate grasping postures of their fingers. When humans grasp the same part of an object, different poses of the palm will cause them to select different grasping postures. Inspired by these human skills, in this article, we propose new grasping posture prediction networks (GPPNs) with multiple inputs, which acquire information from the object image and the palm pose of the dexterous hand to predict appropriate grasping postures. The GPPNs are further combined with grasping rectangle detection networks (GRDNs) to construct multilevel convolutional neural networks (ML-CNNs). In this study, a force-closure index was designed to analyze the grasping quality, and force-closure grasping postures were generated in the GraspIt! environment. Depth images of objects were captured in the Gazebo environment to construct the dataset for the GPPNs. Herein, we describe simulation experiments conducted in the GraspIt! environment, and present our study of the influences of the image input and the palm pose input on the GPPNs using a variable-controlling approach. In addition, the ML-CNNs were compared with the existing grasp detection methods. The simulation results verify that the ML-CNNs have a high grasping quality. The grasping experiments were implemented on the Shadow hand platform, and the results show that the ML-CNNs can accurately complete grasping of novel objects with good performance.

[Metal-organic framework UiO-67-based enrichment and purification of progesterone residues in milk].

Progesterone functions as an endocrine-disrupting compound. Imitating endogenous hormones disrupt the animals' hormone levels. The potential hazard of progesterone in milk cannot be neglected. Thus, research has focused on establishing an efficient and convenient pretreatment and analytical approach. In this study, a metal-organic framework (MOF) material UiO-67 was prepared, which possessed a large specific surface area and excellent stability. It was employed to enrich and purify trace progesterones in a complex milk matrix as a filler to integrate the solid phase extraction column. An approach based on MOF was developed using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). This approach could simultaneously determine seven kinds of progesterone residues in milk. The element spectra of UiO-67 were first measured and analyzed using X-ray photoelectron spectroscopy. The chemical interaction between UiO-67 and progesterone was proved by comparing the changes in binding energy and relative contents of functional groups, and the adsorption efficiency of 1 mg/L and 5 mg/L progesterones by UiO-67 was studied. The adsorption efficiencies of UiO-67 for 1 mg/L and 5 mg/L progesterones were 99.73%-99.95% and 88.87%-99.23%, respectively, according to the results. It proved the efficient adsorption of UiO-67 to progesterones and ensured that subsequent studies went smoothly. Furthermore, key parameters, such as the amount of sorbent, elution solvent type, and pH value, were examined and optimized to obtain optimal extraction recovery of the progesterones. Spiked concentrations of 50 µg/L were employed for extraction optimization. All experiments were performed three times. It also evaluated the matrix effect on mass spectrum signal of the progesterones. The optimized results showed that the seven progesterones could be satisfactorily recovered when the amount of adsorbent was 40 mg, pH value of the sample solution was 5, and elution solution was 5-mL acetone. Additionally, the matrix effect of progesterone in the milk sample was <20%. The matrix effect could be neglected using the aforementioned approach to extract and purify progesterones in milk. Finally, the seven progesterones showed good linearity between 1 and 100 µg/L under the optimized conditions, with linear correlation coefficients values >0.99. The limits of detection (LODs) ranged from 0.06 to 0.30 µg/L, and limits of quantification (LOQs) ranged from 0.19 to 1.0 µg/L, respectively. At various concentration levels of progesterones in milk, the recoveries were 87.10%-105.58%, with relative standard deviations of 2.66%-9.64%. Most importantly, the approach was successfully employed to determine progesterone levels in milk samples, with results in good agreement with the standard SN/T 1980-2007. The proposed approach had the advantages of high sensitivity and satisfactory accuracy compared with the reported pretreatment and detection approaches of progesterone in milk. Satisfactory experimental results can be obtained without the calibration by isotope inner standard. Meanwhile, considering the excellent performance of MOF materials in reducing matrix interference in complex samples, such the application of materials offers a new approach. It can be employed to enrich and detect hazards in a complex matrix in the future.

An all-round AI-Chemist with a scientific mind.

The realization of automated chemical experiments by robots unveiled the prelude to an artificial intelligence (AI) laboratory. Several AI-based systems or robots with specific chemical skills have been demonstrated, but conducting all-round scientific research remains challenging. Here, we present an all-round AI-Chemist equipped with scientific data intelligence that is capable of performing basic tasks generally required in chemical research. Based on a service platform, the AI-Chemist is able to automatically read the literatures from a cloud database and propose experimental plans accordingly. It can control a mobile robot in-house or online to automatically execute the complete experimental process on 14 workstations, including synthesis, characterization and performance tests. The experimental data can be simultaneously analysed by the computational brain of the AI-Chemist through machine learning and Bayesian optimization, allowing a new hypothesis for the next iteration to be proposed. The competence of the AI-Chemist has been scrutinized by three different chemical tasks. In the future, the more advanced all-round AI-Chemists equipped with scientific data intelligence may cause changes to the landscape of the chemical laboratory.

[Effect of PTU on the expression of thyroid TPO, Tg mRNA in rats].

OBJECTIVE: To explore the mechanism and the compensation proceeding of thyroid hyperplasia caused by PTU. METHODS: PTU was administered to rats by gavage at a dose of 5.0 mg/kg B. W for 3, 6, 9, 12, 15, 18, 21 days respectively. All animals were sacrificed after the last dosage, and the expression of TPO and Tg in thyroid was detected by RT-PCR. The serum thyroid hormones were measured by chemoluminescence. RESULTS: Compared with the control group, the TPO mRNA levels of PTU groups were increased, while the Tg mRNA levels were decreased significantly. Serum TT3, TT4 in rats treated with PTU demonstrated a descending trend, while serum TSH showed an ascending trend, and the significant differences were observed after 6 days treating with PTU. CONCLUSION: The interference of PTU on thyroid may relate to inhibiton of Tg gene transcription. The enhancement of TPO gene transcription can't compensate the thyroid function sufficiently.

MiR-182-5p inhibits colon cancer tumorigenesis, angiogenesis, and lymphangiogenesis by directly downregulating VEGF-C.

MicroRNAs (miRNAs) are gene modulators essential for biological processes. However, the precise functions of miRNAs in growth and development of colon cancer are still elusive. To clarify their role, here we analyzed a miRNA microarray of colon cancer. MiR-182-5p was found markedly downregulated in colon cancer tissues and cells, and strongly correlated with pathological stage, differentiation, and lymphatic metastasis. In vitro, miR-182-5p overexpression repressed colon cancer cell proliferation, colony formation, migration, and invasion, and triggered G1 arrest and apoptosis. MiR-182-5p overexpression also downregulated vascular endothelial growth factor (VEGF)-C and inhibited the activity of a luciferase reporter containing the VEGF-C 3'-untranslated region. Moreover, miR-182-5p overexpression in colon cancer cells and human umbilical vein endothelial cells (HUVECs) downregulated VEGF-A as well as VEGF receptor (VEGFR)-2 and VEGFR-3, thereby inhibiting the phosphorylation of ERK and AKT. In vivo, miR-182-5p overexpression strikingly suppressed oncogenicity of SW620 cells as well as angiogenesis and lymphangiogenesis of xenograft tumors in nude mice. These data indicate that miR-182-5p regulates colon cancer tumorigenesis partially through modulating angiogenesis and lymphangiogenesis by targeting VEGF-C, and inhibiting ERK and AKT signaling pathways.