Exosomal long non-coding RNA AU020206 alleviates macrophage pyroptosis in atherosclerosis by suppressing CEBPB-mediated NLRP3 transcription.

Recent studies have suggested exosomes (EXO) as potential therapeutic tools for cardiovascular diseases, including atherosclerosis (AS). This study investigates the function of bone marrow stem cell (BMSC)-derived exosomes (EXO) on macrophage pyroptosis in AS and explores the associated mechanism. BMSC-EXO were isolated from healthy mice and identified. RAW264.7 cells (mouse macrophages) were exposed to oxLDL to simulate an AS condition. BMSC-EXO treatment enhanced viability and reduced lactate dehydrogenase release of macrophages. An animal model of AS was established using ApoE-/- mice. BMSC-EXO treatment suppressed plaque formation as well as macrophage and lipid infiltration in mouse aortic tissues. Moreover, BMSC-EXO decreased concentrations of pyroptosis-related markers interleukin (IL)-1ß, IL-18, cleaved-caspase-1 and gasdermin D in vitro and in vivo. Long non-coding RNA AU020206 was carried by the BMSC-EXO, and it bound to CCAAT enhancer binding protein beta (CEBPB) to block CEBPB-mediated transcriptional activation of NLR family pyrin domain containing 3 (NLRP3). Functional assays revealed that silencing of AU020206 aggravated macrophage pyroptosis and exacerbated AS symptoms in mice. These exacerbations were blocked upon CEBPB silencing but then restored after NLRP3 overexpression. In conclusion, this study demonstrates that AU020206 delivered by BMSC-EXO alleviates macrophage pyroptosis in AS by blocking CEBPB-mediated transcriptional activation of NLRP3.

METTL14 mediates nerve growth factor-stimulated testosterone synthesis in porcine theca cells†.

Ovarian theca cells produce testosterone, which acts as a vital precursor substance for synthesizing estrogens during follicular development. Nerve growth factor (NGF) has been shown to participate in reproductive physiology, specifically to follicular development and ovulation. There is currently no available data on the impact of NGF on testosterone synthesis in porcine theca cells. Furthermore, m6A modification is the most common internal modification in eukaryotic mRNAs that are closely associated with female gametogenesis, follicle development, ovulation, and other related processes. It is also uncertain whether the three main enzymes associated with m6A, such as Writers, Erasers, and Readers, play a role in this process. The present study, with an in vitro culture model, investigated the effect of NGF on testosterone synthesis in porcine theca cells and the role of Writers-METTL14 in this process. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells. This study will help to further elucidate the mechanisms by which NGF regulates follicular development and provide new therapeutic targets for ovary-related diseases in female animals. Summary Sentence  The present study investigated the effect of NGF on testosterone synthesis in porcine theca cells. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells.

Effects of uric acid-lowering therapy (ULT) on renal outcomes in CKD patients with asymptomatic hyperuricemia: a systematic review and meta-analysis.

BACKGROUND: It is well known that asymptomatic hyperuricemia and gout play an important role in patients with chronic kidney disease (CKD). However, the effect of uric acid-lowering therapy (ULT) on the prognosis of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, we aim to investigate the influence of ULT on renal outcomes in these patients. METHODS: Comprehensive searches were conducted in PubMed, EMBASE, China National Knowledge Internet (CNKI), and the Cochrane Library, up until January 2024. We included randomized controlled trials (RCTs) that evaluated the effects of ULT on renal outcomes in CKD patients with asymptomatic hyperuricemia. RESULTS: A total of 17 studies were included in the meta-analysis. Compared with placebo or no treatment, ULT preserved the loss of estimated glomerular filtrating rate (eGFR) (Weighted mean difference [WMD] and its 95% confidence intercal(CI): 2.07 [0.15,3.98] mL/min/1.73m2) at long-term subgroup. At the same time, short-term subgroup also proved the preserved loss of eGFR (WMD 5.74[2.09, 9.39] mL/min/1.73m2). Compared with placebo or no treatment, ULT also reduced the increase in serum creatinine (Scr) at short-term (WMD -44.48[-84.03,-4.92]µmol/L) subgroup and long-term (WMD -46.13[-65.64,-26.62]µmol/L) subgroup. ULT was associated with lower incidence of the events of doubling of Scr without dialysis (relative risk (RR) 0.32 [0.21, 0.49], p < 0.001). However, no difference was found for lower incidence of acute kidney injury (AKI) (p = 0.943). CONCLUSIONS: According to our study, ULT is beneficial for slowing CKD progression both in short to long-term follow-ups. Additionally, in patients younger than 60 years old, the protective effect of ULT on renal outcome is more pronounced. However, it showed no significant difference in the incidence of AKI. These findings underscore the importance of considering ULT in clinical strategies for CKD patients with asymptomatic hyperuricemia.

CCN6 improves hepatic steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis.

BACKGROUND AND AIMS: CCN6 is a secretory protein with functions of maintaining mitochondrial homeostasis and anti-oxidative stress; and yet, whether it is involved in the pathogenesis of non-alcoholic steatohepatitis (NASH) is still obscure. We investigated the role and mechanism of CCN6 in the development of NASH. METHODS: Human liver tissue samples were collected to detect the expression profile of CCN6. High-fat-high-cholesterol (HFHC) and methionine choline-deficient (MCD) diet were applied to mice to establish NASH animal models. Liver-specific overexpression of CCN6 was induced in mice by tail vein injection of adeno-associated virus (AAV), and then the effect of CCN6 on the course of NASH was observed. Free fatty acid (FFA) was applied to HepG2 cells to construct the cell model of steatosis, and the effect of CCN6 was investigated by knocking down the expression of CCN6 through small interfering RNA (siRNA) transfection. RESULTS: We found that CCN6 expression was significantly downregulated in the liver of NASH. We confirmed that liver-specific overexpression of CCN6 significantly attenuated hepatic steatosis, inflammation response and fibrosis in NASH mice. Based on RNA-seq analysis, we revealed that CCN6 significantly affected the MAPK pathway. Then, by interfering with apoptosis signal-regulating kinase 1 (ASK1), we identified the ASK1/MAPK pathway pairs as the targets of CCN6 action. CONCLUSIONS: CCN6 protects against hepatic steatosis, inflammation response and fibrosis by inhibiting the activation of ASK1 along with its downstream MAPK signalling. CCN6 may be a potential therapeutic target for the treatment of NASH.

Model-based analysis of the incidence trends and transmission dynamics of COVID-19 associated with the Omicron variant in representative cities in China.

BACKGROUND: In 2022, Omicron outbreaks occurred at multiple sites in China. It is of great importance to track the incidence trends and transmission dynamics of coronavirus disease 2019 (COVID-19) to guide further interventions. METHODS: Given the population size, economic level and transport level similarities, two groups of outbreaks (Shanghai vs. Chengdu and Sanya vs. Beihai) were selected for analysis. We developed the SEAIQRD, ARIMA, and LSTM models to seek optimal modeling techniques for waves associated with the Omicron variant regarding data predictive performance and mechanism transmission dynamics, respectively. In addition, we quantitatively modeled the impacts of different combinations of more stringent interventions on the course of the epidemic through scenario analyses. RESULTS: The best-performing LSTM model showed better prediction accuracy than the best-performing SEAIQRD and ARIMA models in most cases studied. The SEAIQRD model had an absolute advantage in exploring the transmission dynamics of the outbreaks. Regardless of the time to inflection point or the time to Rt curve below 1.0, Shanghai was later than Chengdu (day 46 vs. day 12/day 54 vs. day 14), and Sanya was later than Beihai (day 16 vs. day 12/day 20 vs. day 16). Regardless of the number of peak cases or the cumulative number of infections, Shanghai was higher than Chengdu (34,350 vs. 188/623,870 vs. 2,181), and Sanya was higher than Beihai (1,105 vs. 203/16,289 vs. 3,184). Scenario analyses suggested that upgrading control level in advance, while increasing the index decline rate and quarantine rate, were of great significance for shortening the time to peak and Rt below 1.0, as well as reducing the number of peak cases and final affected population. CONCLUSIONS: The LSTM model has great potential for predicting the prevalence of Omicron outbreaks, whereas the SEAIQRD model is highly effective in revealing their internal transmission mechanisms. We recommended the use of joint interventions to contain the spread of the virus.

The effect of spraying bacterial and fungal solutions on Korean pine Pinus koraiensis Sieb. et Zucc. cone development and seed quality when sprayed during the flowering phase.

Korean pine is an economically essential afforestation species limited by the unreasonable collection of cones, indiscriminate use of chemical pesticides and pest damage. This study aimed to determine whether spraying bacterial or fungal solutions affected insect pests, cone development, and the seed quality of Korean pine Pinus koraiensis Sieb. et Zucc. The experiment was conducted in a forest plantation in Linkou County (Heilongjiang, China) in 2019. Four fungal strains and one bacterial strain were applied during the flowering phase of Korean pine. The results after a year and a half of study indicated that a high concentration of Bacillus thuringiensis 223176 promoted cone development, increased seed weight, and reduced the proportion of damaged cones. Under this treatment, there were 15.873% damaged cones; the seed weight reached 0.829 g, and there were 82.738% fully developed cones. Trees treated with the second most effective strain, Beauveria bassiana 122077, had 30.556% damaged cones and an average seed weight of 0.810 g. Leucanicillium antillanum 01 performed the worst in this study. The seed weight was only 0.775 g, and the damaged and fully developed cones were 52.444 and 41.773%, respectively. In summary, spraying bacterial or fungal solutions during the flowering stage of Korean pine positively impacted seed quality and effectively decreased damage by the lepidopteran species that feed on the cones and seeds in this study.

The role of pulse indicator continuous cardiac output (PiCCO) and critical care ultrasound in volume status assessment during fluid resuscitation for and prognosis of septic shock patients.

Objectives: To investigate whether pulse index continuous cardiac output (PiCCO) and critical care ultrasound are highly consistent in volume status assessment during fluid resuscitation for septic shock patients and analyze their influence on the prognosis of septic shock. Methods: Eighty septic shock patients treated by Huizhou Central People's Hospital during December 2018 and December 2020 were included and divided into a study group and a control group by the presence of volume responsiveness, with each group having 40 patients. The control group was subject to PiCCO-guided fluid resuscitation therapy, while the study group was given fluid resuscitation therapy guided by critical care ultrasound. Cardiac output, cardiac function, and catheter-related infection (CRI) were documented for intergroup comparison to confirm whether these two techniques were consistent with each other regarding their effects on resuscitation for and prognosis of septic shock patients. Results: Mechanical ventilation duration (MVD) and intensive care unit (ICU) length of stay (LoS) were significantly shorter in the study group when compared with the control group, and the differences were statistically significant (p<0.05, respectively). In terms of blood pressure parameters, the two groups did not differ greatly in diastolic blood pressure (DBP), mean arterial pressure (MAP), systolic blood pressure (SBP), and central venous pressure (CVP) before resuscitation (p>0.05, respectively); at 6h(six hour) after resuscitation, DBP, MAP, SBP, and CVP were substantially increased in both groups as compared with the pre-resuscitation levels (all p<0.05), but the differences between the two groups lacked statistical significance (all p>0.05). Comparing urine volume and degrees of positive fluid balance at 6 h and 12 h after resuscitation, drastic increases in urine volume and positive fluid balance were observed in both groups at 12 h as compared with at 6 h (all p<0.05); nevertheless, the two groups showed no statistically significant difference in urine volume and positive fluid balance at 6 h or 12 h (p>0.05, respectively). With regards to prognosis, there was no statistically significant difference between the two groups in the number of cases of continuous renal replacement therapy (CRRT), dosage of vasoactive agents and 28-d mortality rate (all p>0.05). However, the incidence of CRI was markedly lower in the study group (0/40) as compared with the control group (5/40), and the difference was statistically significant (p<0.05). Conclusions: Both PiCCO and critical care ultrasound can help achieve favorable outcomes from resuscitation for septic shock patients. Compared with PiCCO, critical care ultrasound monitoring appears to be more effective in preventing CRI and reducing MVD and ICU LoS, thereby easing patients' medical burden.

Lycium barbarum polysaccharide improves dopamine metabolism and symptoms in an MPTP-induced model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly populations, whereas there is no cure for PD so far. Novel animal models and medications await development to elucidate the aetiology of PD and attenuate the symptoms, respectively. METHODS: A neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was used in the current study to establish a PD pathologic model in silkworms. The time required to complete specific behaviours was recorded. Dopamine content was detected by ultra-performance liquid chromatography (UPLC). The activity of insect tyrosine hydroxylase (TH) was determined using a double-antibody sandwich method. Oxidative stress was assessed by changes in antioxidant enzyme activity and the content of oxidative products. RESULTS: MPTP-treated silkworms were characterized by impaired motor ability, reduced dopamine content, and elevated oxidative stress level. The expression of TH, a dopamine biosynthetic enzyme within dopaminergic neurons in the brain, was significantly reduced, indicating that dopaminergic neurons were damaged. Moreover, MPTP-induced motility impairment and reduced dopamine level in the silkworm PD model could be rescued after feeding a combination of levodopa (L-dopa [LD]) and carbidopa (CD). MPTP-induced oxidative damage was also alleviated, in ways consistent with other PD animal models. Interestingly, administration of Lycium barbarum polysaccharide (LBP) improved the motor ability, dopamine level, and TH activity, and the oxidative damage was concomitantly reduced in the silkworm PD model. CONCLUSIONS: This study provides a promising animal model for elucidating the pathogenesis of PD, as well as a relevant preliminary drug screening (e.g., LBP) and evaluation.

Emerging Trends and Research Foci in Artificial Intelligence for Retinal Diseases: Bibliometric and Visualization Study.

BACKGROUND: Patients with retinal diseases may exhibit serious complications that cause severe visual impairment owing to a lack of awareness of retinal diseases and limited medical resources. Understanding how artificial intelligence (AI) is used to make predictions and perform relevant analyses is a very active area of research on retinal diseases. In this study, the relevant Science Citation Index (SCI) literature on the AI of retinal diseases published from 2012 to 2021 was integrated and analyzed. OBJECTIVE: The aim of this study was to gain insights into the overall application of AI technology to the research of retinal diseases from set time and space dimensions. METHODS: Citation data downloaded from the Web of Science Core Collection database for AI in retinal disease publications from January 1, 2012, to December 31, 2021, were considered for this analysis. Information retrieval was analyzed using the online analysis platforms of literature metrology: Bibliometrc, CiteSpace V, and VOSviewer. RESULTS: A total of 197 institutions from 86 countries contributed to relevant publications; China had the largest number and researchers from University College London had the highest H-index. The reference clusters of SCI papers were clustered into 12 categories. "Deep learning" was the cluster with the widest range of cocited references. The burst keywords represented the research frontiers in 2018-2021, which were "eye disease" and "enhancement." CONCLUSIONS: This study provides a systematic analysis method on the literature regarding AI in retinal diseases. Bibliometric analysis enabled obtaining results that were objective and comprehensive. In the future, high-quality retinal image-forming AI technology with strong stability and clinical applicability will continue to be encouraged.

pH-Regulated H4TCPE@Eu/AMP ICP Sensor Array and Its Fingerprinting on Test Papers: Toward Point-of-Use Systematic Analysis of Environmental Antibiotics.

In this work, 1,1,2,2-tetra(4-carboxylphenyl)ethylene (H4TCPE) was selected as the guest and incorporated into a Eu/AMP ICP host to establish a "lab-on-an-AIE@Ln/ICP" sensor array for identifying and sensing environmental antibiotics simultaneously. First, on the basis of a theoretical study of the antenna effect and reductive photoinduced charge transfer between the as-prepared H4TCPE@Eu/AMP ICPs and antibiotics, respectively, the response from the sensitized time-resolved fluorescence of the host and the unique aggregation-induced emission (AIE) of the guest were selected as the main sensing elements for the sensor array. With the regulation of pH, the diverse fluorescence responses for antibiotics with either structural differences (flumequine, oxytetracycline, and sulfadiazine) or structural similarities (oxytetracycline, tetracycline, and doxycycline) were recorded and processed by principal component analysis; systematic analysis of environmental antibiotics was therefore realized. Encouraged by the superior anti-aggregation-caused quenching effect of H4TCPE@Eu/AMP ICPs on the test strip, the distinct fluorescence color changes of the "lab-on-an-AIE@Ln/ICP" sensor array were further explored with the aid of smartphones. The fingerprinting pattern of the sensor array on test paper eventually holds great potential for the point-of-use systematic analysis of environmental antibiotics even in complicated real samples.

Lab-on-a-ZnO-Submicron-Particle Sensor Array for Monitoring AD upon Cd2+ Exposure with CSF Tau441% as an Effective Hallmark.

In this study, based on the posttreatment strategy, blue-color-emissive ZnO submicron particles (B-ZnO SMPs) and red-color-emissive ZnO submicron particles (R-ZnO SMPs) were obtained from rationally designed Zn-infinite coordination polymer (ICP) precursors. After modification of thiol-containing aptamers, diverse spectral changes in the ultraviolet and visible regions of B- and R-ZnO SMPs toward different tau species were explored to construct a lab-on-a-ZnO-submicron-particle sensor array. Assisted by principal component analysis (PCA), the unique fingerprints of the sensor array enabled the simultaneous differentiation and quantitative detection of different tau species (tau381, tau410, and tau441) for the first time. Furthermore, the dynamic changes of tau441% (the ratio of the two most reported representative 4R isoform (full-length tau441) and 3R isoform (tau381)) in cerebrospinal fluid (CSF) during the Alzheimer's disease (AD) onset of Cd2+-exposed rats could also be monitored by the lab-on-a-ZnO-submicron-particle sensor array, which was supposed to be an effective hallmark and highly correlated with the formation of neurofibrillary tangles (NFTs). This study not only provides a further insight into the involvement of subchronic Cd2+ exposure in the tau etiology of AD but also offers more comprehensive and effective information about the asymptomatic stage of AD upon environmental risk, which has potential applications in the early diagnosis and therapy.

Construction of Highly Proton-Conductive Zr(IV)-Based Metal-Organic Frameworks From Pyrrolo-pyrrole-Based Linkers with a Rhombic Shape.

To date, numerous zirconium cluster-based metal-organic frameworks (Zr-MOFs) with attractive physical properties have been achieved thanks to tailorable organic linkers and versatile Zr clusters. Nevertheless, in comparison with the most-used high-symmetry organic linkers, low-symmetry linkers have rarely been exploited in the construction of Zr-MOFs. Despite challenges in predicting the structure and topology of the MOF, linker desymmetrization presents opportunities for the design of Zr-MOFs with unusual topologies and unexpected functionalities. Herein, we report for the first time the construction of two robust Zr-MOFs (IAM-7 and IAM-8) from two pyrrolo-pyrrole-based low-symmetry tetracarboxylate linkers with a rare rhombic shape. The low symmetry of the linkers arises from the asymmetric pyrrolo-pyrrole core and the varying branch lengths, which play a critical role in the structural diversity between IAM-7 and IAM-8 seen from the structural analysis and lead to hydrophilic channels that contain uncoordinated carboxylate groups in the structure of IAM-7. Furthermore, the proton conductivity of IAM-7 displays a high temperature and humidity dependence where the proton conductivity increases from 2.84 × 10-8 S cm-1 at 30 °C and 40% relative humidity (RH) to 1.42 × 10-2 S cm-1 at 90 °C and 95% RH, making it among one of the most conductive Zr-MOFs. This work not only enriches the library of Zr-MOFs but also offers a platform for the design of low-symmetry linkers toward the structural diversity or irregularity of MOFs as well as their structure-related properties.

Hypoglycemic effect of low-sugar juice derived from Hovenia dulcis on type 1 diabetes mellitus rats.

BACKGROUND: Fruit juice is usually rich in monosaccharides and disaccharides. A reverse osmosis separation machine was used to remove monosaccharides and disaccharides from Hovenia dulcis fruit juice, leaving behind most of the bioactive substances in a low-sugar fruit juice (LSFJ), so as to provide a more effective treatment for diabetic patients. METHOD: This study was carried out with type 1 diabetes mellitus model induced with high dose of streptozotocin (60 mg kg-1 ), and oral administration of LSFJ for 4 weeks. RESULTS: LSFJ treatment led to significant gain in body weight and increased serum insulin level, insulin-like growth factor-1 level, blood urea nitrogen level, creatinine level, and hepatic glycogen level. Meanwhile, fasting blood glucose, fructosamine level, and glucose tolerance were also observably enhanced. Additional, LSFJ treatment significantly improved lipid metabolism, islet quality, and islet oxidative stress. The messenger RNA levels of glucose metabolism genes in the pancreas of diabetic rats decreased in the diabetes model group, whereas messenger RNA expression of these genes was significantly increased with LSFJ treatment. CONCLUSION: These findings indicate that LSFJ can improve symptoms associated with type 1 diabetes mellitus. The research also suggests new strategies for diabetes prevention and treatment. © 2021 Society of Chemical Industry.

Effects of ethephon on ethephon residue and quality properties of chili pepper during pre-harvest ripening.

The application of ethephon was investigated to examine its effects on both ethephon residue and quality properties of chili peppers during pre-harvest ripening with the goal of facilitating maximum commercial harvest along with improving color and flavor. A single ethephon treatment significantly increased L* and a* values and capsanthin concentration, while decreased total chlorophyll contents. Moreover, ethephon treatment induced significant promotion of capsaicin synthesis and reduction of soluble sugar content. While repeated treatments did not increase the total capsaicin content, and the consumption of soluble sugar was accelerated. Additionally, the maximum ethephon residue in chili pepper after ethephon treatment was 21.18 mg kg-1, which is lower than the permissible residue level of 50 mg kg-1 for chili peppers. The ethephon residual decreased with prolonging harvest time of chili peppers. The effects of ethephon treatment on different types of chili peppers were variable. The results of this study indicated that ethephon could hasten the ripening process and increase the quality of chili peppers.

Stimulus Response of TPE-TS@Eu/GMP ICPs: Toward Colorimetric Sensing of an Anthrax Biomarker with Double Ratiometric Fluorescence and Its Coffee Ring Test Kit for Point-of-Use Application.

In this work, by fully exploring the stimulus response of infinite coordination polymer nanoparticles (ICPs) and by taking advantage of the particular optical properties of ICP guest tetra(4-sulfophenyl)ethene (TPE-TS) with adjustable monomer emission (ME) and aggregation-induced emission (AIE), we demonstrated a novel sensing mechanism for an anthrax biomarker dipicolinic acid (DPA) based on the competitive coordination interaction regulating the structure of TPE-TS@Eu/GMP ICPs. The double ratiometric fluorescence stemmed from triple response of TPE-TS@Eu/GMP ICPs without spectral cross-interference (ME and AIE from TPE-TS and sensitized emission from Eu/DPA) and a corresponding blue-to-red fluorescent color change, which not only benefited the direct detection of DPA with high sensitivity and selectivity, but also offered a great opportunity to realize real-time monitoring of DPA released by Bacillus subtilis spores. Furthermore, the coffee ring deposition patterns on a test paper were innovatively tuned by the quantity and morphology changes of TPE-TS@Eu/GMP ICPs during their stimulus response toward DPA, which could be exploited as expanded signal channels. By integrating a multichannel responsive coffee ring test kit with image recognition and processing application installed on smartphones, point-of-use analysis of DPA could be realized in a low-cost and high-throughput fashion.

A smartphone-based platform for point-of-use determination of alkaline phosphatase as an indicator of water eutrophication.

A smartphone-based detection platform for the determination of alkaline phosphatase (ALP) is described. The method is based on the rational design of the stimulus-response of 7-methoxycoumarin-3-carboxylic acid (7-MC-3-COOH)-functionalized Eu-AMP infinite coordination polymer (ICP) nanoparticles. The blue fluorescence of 7-MC-3-COOH at 403 nm was suppressed, while the red fluorescence of Eu3+ at 615 nm was sensitized after the formation of 7-MC-3-COOH@Eu-AMP ICP. Upon exposure to ALP, the dephosphorylation of AMP resulted in the destruction of 7-MC-3-COOH@Eu-AMP ICP, and thereby, the blue fluorescence of 7-MC-3-COOH recovered; in the meantime, the sensitized red fluorescence was quenched. With the fluorescence intensity ratio F615/F430 as the signal readout, ALP can be detected within a concentration range 0.001 to 0.15 U mL-1, and the limit of detection (LOD) was 0.00035 U mL-1. Moreover, fluorescence color changes from red to blue could also be recognized by a portable device with the smartphone as a signal reader, and direct point-of-use testing (POUT) for ALP within a concentration range 0.005 to 0.7 U mL-1 could be realized, with LOD of 0.0015 U mL-1. Endowed with high sensitivity and superior reliability, the assay enabled direct monitoring of P-related water eutrophication in a freshwater lake with ALP as an indicator. Graphical abstract A smartphone-based platform for point-of-use determination of alkaline phosphatase.

Tumor Necrosis Factor Ligand-Related Molecule 1A Regulates the Occurrence of Colitis-Associated Colorectal Cancer.

BACKGROUND: Tumor necrosis factor ligand-related molecule 1 A (TLlA) is closely related to the occurrence and development of inflammatory bowel disease. AIMS: We aimed to explore whether TLlA was involved in the occurrence of colitis-associated colorectal cancer (CAC). METHODS: Firstly, azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to construct the CAC mice model in wild-type (WT) and TL1A transgenic (Tg) mice with TL1A high expression. The histopathological analysis was used for the evaluation of inflammation level, and the immunohistochemistry staining analysis was used to test the expression and location of proliferating cell nuclear antigen (PCNA) and ß-catenin. Secondly, the HCT116 and HT29 cell lines were used for knockdown of TL1A gene for further assay including cell viability, cell clone, cell apoptosis and matrigel invasion. Western blot were used for quantitative protein expression of ß-catenin and downstream oncogenes including c-myc and Cyclin D1 after knockdown of TL1A gene. RESULTS: The evaluation of inflammation level showed that the disease activity index score and tumor formation rate were significantly higher in AOM + DSS/Tg group than that in AOM + DSS/WT group. The expression of PCNA, ß-catenin, c-myc, and Cyclin D1 in AOM + DSS/Tg group was significantly higher than that in AOM + DSS/WT group. The cell experiment showed that TL1A knockdown inhibited the cell proliferation, invasion, and migration. Moreover, the expression of c-myc and Cyclin D1 was significantly decreased after TL1A knockdown. CONCLUSIONS: TL1A can induce tumor cell proliferation and promote the occurrence of CAC by activating Wnt/ß-catenin pathway.

Protocol for the Generation of Human EPS-Blastoids Using a Three-Dimensional Two-Step Induction System.

Stem cell-derived embryos in vitro allow the exploration of the very early stages of human embryogenesis in vitro and are thus promising for widespread applications in developmental biology, related developmental disease modeling, and drug discovery. Several cell resources have been utilized, with different efficiencies and methods for generating human blastoids, a structure similar to natural blastocysts. Human EPS cells were reported to contribute to the embryonic and extraembryonic lineages and therefore can be a practical and efficient cell resource for constructing human blastoids. Here, we developed a three-dimensional, two-step induction system for generating human blastoids using human EPS cells. According to morphological and transcriptomic analysis, EPS-blastoids recapitulate the key developmental processes and cell lineages of human blastocysts. Moreover, in vitro extended culture for 8 and 10 days of EPS-blastoids can result in postimplantation embryonic structures. In this chapter, we describe a protocol that covers the generation, maintenance, and developmental phenocopying of human EPS blastoids.

TL1A promotes metastasis and EMT process of colorectal cancer.

Background: Metastasis is the major problem of colorectal cancer (CRC) and is correlated with the high mortality. Tumor necrosis factor-like cytokine 1A (TL1A) is a novel regulatory factor for inflammatory diseases. This work aimed to investigate the role of TL1A in CRC metastasis. Method: AOM/DSS-induced mouse model, xenograft tumor model and metastasis murine model were established to mimic the colitis-associated CRC and investigate CRC growth and metastasis in vivo. Colon tissues were assessed by hematoxylin/eosin (HE) staining and immunohistochemistry (IHC). CRC cell metastasis in vivo was observed using in vivo imaging system (IVIS). Cell viability and proliferation were examined using cell counting kit 8 (CCK-8) and EdU experiments. The expression of tumor growth factor ß (TGFß) and metastatic biomarkers were detected using western blotting experiment. The in vitro cell metastasis was measured by Transwell. Results: Knockdown of TL1A notably suppressed the generation of colonic tumors in azoxymethane/dextran sodium sulfate (AOM/DSS) model, suppressed in vivo CRC cell growth, as well as lung and liver metastasis. The inflammation response and inflammatory cell infiltration in tumor sites were decreased by TL1A depletion. The in vitro CRC cell growth and metastasis was also suppressed by shTL1A, along with altered expression of epithelial mesenchymal transition (EMT) biomarkers. TL1A depletion suppressed the level of the TGF-ß1 receptor (TßRI) and phosphorylation of Smad3 in CRC cells. Stimulation with TGF-ß recovered the CRC cell migration and invasion that suppressed by shTL1A. Conclusion: Our work implicated TL1A as a promoter of CRC generation and metastasis and defines TGF-ß/Smad3 signaling as mediator of TL1A-regualated CRC cell metastasis.

Visible-light-induced photocatalyst-free cascade cyclization of 3-(2-(ethynyl)phenyl)quinazolinones to sulfonated quinolino[2,1-b]quinazolinones.

A visible-light-induced K2S2O8-promoted cascade sulfonation/cyclization reaction was established using 3-(2-(ethynyl)phenyl)quinazolinones as efficient substrates under mild conditions. A series of sulfonated quinolino[2,1-b]quinazolinones were successfully synthesized under transition-metal- and photocatalyst-free conditions. Notably, this strategy has the advantages of room temperature and simple operation, easy scale-up, and good functional group tolerance.