Tumor suppressor BAP1 suppresses disulfidptosis through the regulation of SLC7A11 and NADPH levels.

BAP1, BRCA1-Associated Protein 1, serves as a novel tumor suppressor through the deubiquitination of monoubiquitination of H2A and subsequent gene transcriptional regulation. Regulated cell death like apoptosis or ferroptosis is considered an essential mechanism mediating tumor suppression. Previous reports, including ours, have demonstrated that BAP1 could promote apoptosis and ferroptosis to inhibit tumor development. Whether BAP1 regulated additional types of cell death remains unclear. Disulfidptosis is a recently identified novel cell death mode characterized by aberrant accumulation of intracellular disulfide (e.g., cystine) and depletion of NADPH. In this study, we first demonstrated that BAP1 could significantly protect disulfidptosis induced by glucose starvation, which is validated by various cell death inhibitors and the accumulation of disulfide bonds in the cytoskeleton proteins. BAP1 is known to inhibit SLC7A11 expression. We found that the protective effect of BAP1 against disulfidptosis was counteracted when overexpressing SLC7A11 or adding additional cystine. Conversely, BAP1-mediated suppression of disulfidptosis was largely abrogated when SLC7A11-mediated cystine uptake was inhibited by the knockout of SLC7A11 or erastin treatment. Besides, high BAP1 expression showed lower NADP+/NADPH levels, which might confer resistance to disulfidptosis. Consistent with these observations, the expression level of BAP1 was also positively correlated with NADPH-related genes in KIRC patients, though the underlying mechanism mediating NADPH regulation remains further investigation. In summary, our results revealed the role of BAP1 in the regulation disulfidptosis and provided new insights into the understanding of disulfidptosis in tumor development.

Glucose deprivation-induced disulfidptosis in human nucleus pulposus cells: a novel pathological mechanism of intervertebral disc degeneration.

BACKGROUND: Limited supply of certain nutrients and deregulation of nucleus pulposus (NP) plays a key role in the pathogenesis of intervertebral disc degeneration (IVDD). However, whether nutrient deprivation-induced cell death, particularly disulfidptosis, contributes to the depletion of NP cells and the development of IVDD, is unknown. METHODS: RNA-seq, single-cell RNA-seq, and Genome-wide DNA methylation datasets of nucleus pulposus tissue were collected for bioinformatic analysis. Predictive models of disulfidptosis related genes in IVDD were constructed by machine learning and their differential expression was analyzed. In addition, we performed cell subsets identification analysis, cell-cell communications analysis, and functional enrichment analysis of key genes in the core subset based on single-cell RNA-seq data of NP tissues isolated from one normal sample and one IVDD sample. Finally, glucose deprivation-induced disulfidptosis in human NP cells (HNPCs) was verified by various cell death inhibitors and disulfidptosis-related molecular markers. RESULTS: We found the disulfidptosis signal was significantly activated in the IVDD group. Using single-cell RNA-seq analysis, we focused on the chondrocytes and found that disulfidptosis-related genes significantly highly expressed in the IVDD C4 chondrocyte subset, which was identified as a new disulfidptosis-associated cell subset. Correlation analysis revealed the negative correlation between SLC7A11 (driving gene of disulfidptosis) and the glucose transporter GLUTs (SLC2A1-4) family genes (suppressing genes of disulfidptosis) in the IVDD group. We also found obvious cell death in HNPC upon glucose starvation, while employment of various cell death inhibitors could not inhibit glucose starvation-induced death in HNPCs. Moreover, the accumulation of disulfide bonds in cytoskeletal proteins was indicated by slowed migration in non-reducible protein blotting experiments. 2-DG, a key disulfidptosis inhibitor, significantly rescued cell death caused by glucose starvation through lowering the NADP+/NADPH ratio. CONCLUSIONS: We validated the occurrence of disulfidptosis in HPNCs and identified a novel disulfidptosis-associated cell subset, followed by experimental verification of disulfidptosis in a glucose-limited context to mimic a fall in nutrient supply during the development disc degeneration. These findings provided new insights into the pathological mechanisms of IVDD and encourage us to explore potential therapeutic targets involved in the regulation of disulfidptosis for the prevention of intervertebral disc degeneration.

Facile synthesis of hydroxylated triazine-based magnetic microporous organic network for ultrahigh adsorption of phenylurea herbicides: An experimental and density-functional theory study.

Microporous organic networks (MONs) are highly porous materials that are particularly useful in analytical chemistry. However, the use of these materials is often limited by the functional groups available on their surface. Here, we described the polymerization of a sea urchin-like structure material at ambient temperature, that was functionalized with hydroxyl, carboxyl, and triazine groups and denoted as OH-COOH-MON-TEPT. A substantial proportion of OH-COOH-MON-TEPT was intricately decorated EDA-Fe3O4, creating a well-designed configuration (EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC) for superior adsorption of the target analytes phenylurea herbicides (PUHs) via magnetic solid-phase extraction (MSPE). The proposed method showed remarkably low limits of detection ranging from 0.03 to 0.22 ng·L-1. Experimental investigations and theoretical analyses unveiled the adsorption mode between EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC and PUHs. These findings establish a robust foundation for potential applications of EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC in the analysis of various polar contaminants.

The Spatial Spillover Effect of Clean Energy Development on Economic Development: A Case of Theoretical and Empirical Analyses from China.

Does clean energy development (CED) have a spatial spillover effect on economic growth (EG)? Using the panel data of 30 provincial administrative units from 2000 to 2019 in China, this study empirically investigates the spatial spillover effect of CED on EG. From the perspective of the supply side rather than the consumption side, using the spatial Durbin model (SDM), the study finds that CED does not have a significant impact on EG, while there is an apparent positive spillover effect of CED on EG in China, meaning that CED in one province can boost EG in the surrounding provinces. Theoretically, this paper provides a new perspective for studying the relationship between CED and EG. In practice, it provides a reference for further improving the government's future energy policy.

Discovery and Functional Analysis of Secondary Hair Follicle miRNAs during Annual Cashmere Growth.

Secondary hair follicles (SHFs) produce the thermoregulatory cashmere of goats. MicroRNAs (miRNAs) play indispensable roles in hair follicle formation and growth. However, most studies examining miRNAs related to cashmere have been performed on goat skin. It remains unclear which miRNAs are highly expressed in SHFs or how miRNAs affect cashmere growth. In the present study, we isolated the SHFs under a dissecting microscope and analyzed the miRNA signatures during annual cashmere growth. Small-RNA sequencing followed by genome-wide expression analysis revealed that early anagen is a crucial phase for miRNA regulation of the cashmere growth, as revealed by two predominant groups of miRNAs. Although they exhibited opposite expression patterns, both groups demonstrated sharp changes of expression when in transit from early anagen to mid-anagen. In addition, we identified 96 miRNA signatures that were differentially expressed between different phases among 376 miRNAs. Functional analysis of the predicted target genes of highly expressed or differentially expressed miRNAs indicated that these miRNAs were involved in signal pathways associated with SHF development, regeneration, and regression. Furthermore, miR-143-3p was preferentially expressed in SHFs and Itga6 was identified as one of targets. The dual-luciferase and in situ hybridization assay demonstrated that miR-143-3p directly repressed the expression of Itga6, suggesting a possible novel role for miR-143-3p in cashmere growth.

Nitrogen-rich based conjugated microporous polymers for highly efficient adsorption and removal of COVID-19 antiviral drug chloroquine phosphate from environmental waters.

Chloroquine phosphate (CQP) has been suggested as an important and effective clinical reliever medication for the 2019 coronavirus (COVID-19). Nevertheless, its excessive use will inevitably cause irreparable damage to the entire ecosystem, thereby posing a considerable environmental safety concern. Hence, the development of highly-efficient methods of removing CQP from water pollution sources, e.g., effluents from hospitals and pharmaceutical factories is significant. This study reported the fabrication of novel C-N bond linked conjugated microporous polymers (CMPs) (BPT-DMB-CMP) with multiple nitrogen-rich anchoring sites for the quick and efficient removal of CQP from aqueous solutions. The irreversible covalent C-N bond linked in the internal framework of BPT-DMB-CMP endowed it with good chemical stability and excellent adsorbent regeneration. With its predesigned functional groups (i.e., rich N-H bonds, triazine rings, and benzene rings) and large area surface (1,019.89 m2·g-1), BPT-DMB-CMP demonstrated rapid adsorption kinetics (25 min) and an extraordinary adsorption capacity (334.70 mg·g-1) for CQP, which is relatively higher than that of other adsorbents. The adsorption behavior of CQP on BPT-DMB-CMP corresponded with Liu model and mixed-order model. Based on the density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and adsorption comparisons test, the halogen bonding, and hydrogen bonding cooperates with π - π, C - H···π interactions and size-matching effect in the CQP adsorption system on BPT-DMB-CMP. The excellent practicability for the removal of CQP from real wastewater samples verified the prospect of practical application of BPT-DMB-CMP. BPT-DMB-CMP exhibited the application potentials for the adsorption of other antiviral drugs. This work opens up an efficient, simple, and high adsorption capacity way for removal CQP.

Sulfonic acid-functionalized covalent organic frameworks as the coating for stir bar sorptive extraction of fluoroquinolones in milk samples.

Sulfonic acid-functionalized covalent organic frameworks (COF-SO3) as a coating of stir bar sorptive extraction (SBSE) for capturing three fluoroquinolones from milk have been developed. The COF-SO3 material was characterized by X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, and infrared spectroscopy. Milk without any typical treatments like protein precipitation and defatting was only diluted five times with water for test. Combined with high-performance liquid chromatography (HPLC), a SBSE-HPLC method was established for detecting fluoroquinolones in milk samples. The corresponding wide linear ranges (4.00-500.0 µg L-1), low detection limits (1.20-2.62 µg L-1), good test repeatability (RSD < 5.2%), and acceptable enrichment factors (56.2-61.5) were implemented for three fluoroquinolones. The analytical method was applied to determine trace targets and provided satisfactory results. Furthermore, the research displayed satisfied reproducibility for bar-to-bar (RSD < 6.5%) and batch-to-batch (RSD < 8.6%) tests.

Development and Validation of a Method for Determination of 43 Antimicrobial Drugs in Western-Style Pork Products by UPLC-MS/MS with the Aid of Experimental Design.

Western-style pork products have attracted many modern urban consumers, and these products have rapidly entered the Chinese market. The current hazard analysis of processed meat products mainly focuses on processing hazards (PAHs, microorganisms, and food additives), with less attention to veterinary drug residues. According to the survey results, the residues of antimicrobial drugs (sulfonamides and quinolones) in pork and its products in China are a severe problem, which may cause metabolic reactions, toxic effects, or enhance drug resistance. This study applied a modified QuEChERS method combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MSMS) to develop a rapid and sensitive method for determining antimicrobial drugs in bacon and ham was successfully evaluated methodologically by EU 2002/657/EC. This study used a three-level, three-factor Box-Behnken design (BBD) to optimize the QuEChERS method by response surface methodology. The excellent linearity of the calibration curve was shown in the corresponding concentration range with a coefficient of determination greater than 0.99. The values of decision limit (CCα) and detection capability (CCß) were in the range of 10.9-31.3 µg/kg and 11.8-52.5 µg/kg, respectively. The method successfully detected two trace levels of antimicrobial drugs in commercially available samples, including sulfadiazine and moxifloxacin.

Agricultural Insurance and Agricultural Economic Growth: The Case of Zhejiang Province in China.

Based on the theories of welfare economics, this paper analyzed the mechanism of agricultural insurance (AI) affecting agricultural economic growth (AEG), theoretically, and carried out an empirical analysis by using the random effects model and thirteen years of panel data, which included the annual data of 11 cities in Zhejiang Province, China, from 2007 to 2019. The gross output value of agriculture, forestry, animal husbandry, and fishery (GOVA) of 11 cities in Zhejiang Province is selected as the explained variable, agricultural insurance premium income (AIPI) as an explanatory variable. We selected area of waterlogging removal (AWR), rural electricity consumption (REC), total power of agricultural machinery (TPAM), and crop-sown area (CSA) as control variables. The study shows that: (1) the AIPI has a significant positive impact on the growth of GOVA. When other conditions remain unchanged, a 1% increase in AIPI increases the GOVA by 0.166%, accordingly; (2) The control variables of REC, TPAM, and CSA are statistically significant for the growth of the GOVA. The elasticity coefficient of REC is 0.325, the elastic coefficient of the TPAM is 0.287, and the elasticity coefficient of CSA is -0.281.

Does Clean Energy Use Have Threshold Effects on Economic Development? A Case of Theoretical and Empirical Analyses from China.

Increasingly serious energy security and environmental problems have become the main constraints to China's economic development. Therefore, it is critical to explore the threshold effect of clean energy use on China's economic growth. Based on the panel data of 30 Chinese provinces from 2000 to 2019 and using energy intensity (EI) as the threshold variable, this study adopts a panel threshold model to explore the threshold effect of clean energy development on the economy. Empirical results indicate that clean energy has a significant threshold effect on economic development, with the threshold value of EI being 0.7655. When EI is less than 0.7655, clean energy development has a more positive effect on economic growth. When the EI exceeds 0.7655, the impact is significantly positive but with a smaller coefficient. EI weakens the role of clean energy development in promoting economic growth. After 2015, the EI of most provinces in the sample was below the threshold value, which indicates that in recent years, with the economic cost of developing clean energy decreasing, the role of clean energy development in promoting the economy has become more significant. Therefore, we propose policy implications to better promote the effect of clean energy development in promoting economic growth.

[Retracted] MicroRNA­133a acts as a tumour suppressor in breast cancer through targeting LASP1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting assay data shown in Figs. 5B, 5E, 6C and 7A were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 39: 473­482, 2018; DOI: 10.3892/or.2017.6114].

Cationic covalent organic nanosheets for rapid and effective detection of phenoxy carboxylic acid herbicides residue emitted from water and rice samples.

Development of efficient and sensitive adsorbent for capturing phenoxy carboxylic acids (PCAs) from environmental and food samples is necessary because PCAs could threaten human health. Designing nanoparticle with multiple functional groups is beneficial to achieve the strong adsorption interaction and the specific recognition for target compound. In this paper, TpTGCl as an ionic covalent organic framework (ICOF), that could offer plenty of positive charges and hydrogen-bonding sites, was fabricated. TpTGCl achieved quicker, more sensitive enrichment for anionic PCAs. The analysis of binding affinity by density functional theory (DFT) demonstrated that PCAs bonded to TpTGCl primarily via electrostatic attraction, N  H···O and O  H···O, and C  H···π interaction. The quantitative approach indicated low limits of detection (0.016-0.036 ng·g-1 for rice and 0.43-0.78 ng·L-1 for water). Furthermore, successfully determining PCAs emitted from real samples indicated the applicability of TpTGCl.

Highly Ordered, Plasmonic Enhanced Inverse Opal Photonic Crystal for Ultrasensitive Detection of Staphylococcal Enterotoxin B.

Although there is considerable interest in self-assembly of ordered, porous "inverse opal" structures for optical, electronic, and chemical applications, uncontrolled defect formation limits the usefulness of such materials. Herein, we develop a highly ordered and plasmonic enhanced sensing inverse opal photonic crystal (IOPC) material. The co-assembly of the colloidal template with the matrix material avoids the need for liquid penetration into the preassembled colloidal crystals and minimizes the associated rupture and inhomogeneity of the resulting IOPC. Au nanoparticles (Au NPs) not only act as a "bridge" between recognition elements (aptamers) and IOPCs, but also can amplify optical signals. Furthermore, the enhancement mechanism of Au NPs is simulated by COMSOL. During the detection process, the optical signal of the sensing Au-Apt IOPC responds to the Staphylococcal enterotoxin B with a concentration ranging from 10-2 to 103 pg mL-1, and the limit of detection is 2.820 fg mL-1. Spiked real sample detection indicates that the as-proposed method possessed good accuracy. The sensing Au-Apt IOPC provides an extensive biosensor platform to detect a variety of toxic and harmful substances through replacing the aptamer by other recognition elements, such as antibodies or receptors.

Mixed matrix of MOF@COF hybrids for enrichment and determination of phenoxy carboxylic acids in water and vegetables.

A novel mixed matrix of MOF@COF hybrid was firstly formed by coating of hexahedral cage structure MOF with lightweight porous COF, and applied in dispersive solid-phase extraction of the phenoxy carboxylic acids (PCAs) from water and vegetable samples. Combined with liquid chromatography-tandem mass spectrometry, an excellent method with low limits of detection (0.69-1.79 ng·L-1/0.002-0.006 ng·g-1), good reproducibility (1.32%-7.02%/1.81%-6.71%), and excellent linearities (10-1000 ng·L-1, R ≥ 0.9955/0.04-50 ng·g-1, R ≥ 0.9966) was established. The adsorption mechanisms deduced that the π-π interaction, hydrophobic effects, hydrogen bond, and halogen bond may promote the excellent adsorption of the PCAs. Finally, the applicability of the method was verified by spiking four kinds of water and vegetable samples with PCAs, and satisfying recoveries were obtained (between 83.3% and 104.9%).

Ketoenamine Covalent Organic Framework Coating for Efficient Solid-Phase Microextraction of Trace Organochlorine Pesticides.

Fiber coating is a key part of solid-phase microextraction (SPME) technology, and it determines the selectivity, sensitivity, and reproducibility of the analytical method. A ketoenamine covalent organic framework called Tp-Azo-COF with rich electronegative N atoms was prepared as an SPME coating in this work. The Tp-Azo-COF coating had a large surface area of 1218 m2 g-1 and good thermal and chemical stability, and it was applied for the extraction of organochlorine pesticides (OCPs). According to quantum chemistry calculations, the adsorption affinity of the Tp-Azo-COF coating for five OCPs was primarily affected by the halogen bond and hydrophobicity interaction. The extraction efficiencies of the Tp-Azo-COF coating for five OCPs were higher than those of three commercial SPME fiber coatings, and the enrichment factors ranged from 1061 to 3693. When combined with gas chromatography-tandem mass spectrometry, a wide linear range (0.1-1000 ng L-1), low limits of detection (0.002-0.08 ng L-1), and good fiber-to-fiber accuracy (4.3-10.9%) were achieved under optimal conditions. Moreover, the applicability of the developed method was evaluated by analyzing four samples (milk, green tea, tap water, and well water), and the recoveries were in the range of 83.4-101.6%, with relative standard deviations <8.6%. This research extends the application of the stabilized ketoenamine COF as a sample enrichment probe for OCP analysis.

High crystalline magnetic covalent organic framework with three-dimensional grapevine structure for ultrasensitive extraction of nitro-polycyclic aromatic hydrocarbons in food and environmental samples.

Developing and establishing an efficient pre-treatment approach for the precise extraction of nitrated-polycyclic aromatic hydrocarbons (N-PAHs) from real-life samples is critical for ensuring their safety. In this study, a novel crystalline magnetic covalent organic framework with a grapevine structure not a single core-shell, Fe3O4@TAPT-DMTA-COF, was fabricated via chemical bonding. Unchanging the reticulated structure and high crystallinity of TAPT-DMTA-COF, the combination made this material possess not only simple operation via magnetic decantation but also remarkable chemical stability. Fe3O4@TAPT-DMTA-COF had a large surface area (1578.45 m2/g), and rich electronegative triazine-groups, which makes it become a superior magnetic enrichment material for trace N-PAHs. For N-PAHs analysis, low limits of detection (LODs) (1.43-17.24 ng/L), excellent relative standard deviations (RSDs ≤ 11.52%), and wide linearity (10-5000 ng/L) were obtained. Real-life applications based on this composite have been successfully explored by capturing the N-PAHs emitted from food and environmental samples.

Source, transportation, bioaccumulation, distribution and food risk assessment of perfluorinated alkyl substances in vegetables: A review.

Contamination of perfluoroalkyl substances (PFASs) in agricultural products have attracted more and more attentions recently. In this review, relationship between PFASs and vegetables is summarized comprehensively. PFASs could transfer to cultivation soils by irrigation water, bio-amended soil, and atmospheric deposition mainly from industrial emissions. Carbon chain length of PFASs, species of vegetables and so on are key factors for PFASs migration and bioaccumulation in soils, plants and vegetables. Studies on food risk assessment of PFOA and PFOS show low consumption risk for most vegetables, however researches on other substances are lacking. In the future, we need to pay more attention on novel pollution pathway in cultivation, traceability research for considerable contamination, dietary exposure levels for different vegetables and more substances, as well as more exact and scientific food risk assessments. Additionally, effective means for PFASs adsorption in soil and removal from soil are also expected.

Room-temperature synthesis of magnetic covalent organic frameworks for analyzing trace benzoylurea insecticide residue in tea beverages.

A novel magnetic covalent organic framework (NH2-Fe3O4@COF) was prepared using a simple room-temperature synthesis in this study. These magnetic particles exhibited high adsorption performance with short adsorption time (10 min) for six benzoylurea insecticides (BUs) as magnetic solid-phase extraction (MSPE) adsorbents. Quantum chemistry calculation demonstrated that adsorption mechanism was primarily attributed to strong halogen bonds between electronegative O atoms of COF and electropositive F atoms of BUs as well as potential hydrophobic effect. Wide linearities (10-1000 ng·L-1) and low limits of detection (0.06-1.65 ng·L-1) for six analytes were obtained via liquid chromatography-tandem mass spectrometry. Applicability of the proposed method was further evaluated by analyzing four kinds of original tea beverages. Recoveries of six BUs in spiked samples ranged from 80.1% to 108.4%.

A simple and sensitive sensor for lactose based on cascade reactions in Au nanoclusters and enzymes co-encapsulated metal-organic frameworks.

In this work, one kind of zeolite imidazole frameworks containing bovine serum albumin stabilized Au nanoclusters (AuNCs), ß-galactosidase (ß-Gal) and glucose oxidase (GOx) (AuNCs/ß-Gal/GOx@ZIF-8) were obtained to detect lactose. Compared with other fluorescent nano-materials, AuNCs show distinct advantages as a guest species in ZIF-8, specifically their extremely small size (<1 nm), simple synthesis, excellent biocompatibility and high stability. Furthermore, the bovine serum albumin on their surfaces can promote the formation of ZIF-8 coating; thus, AuNCs were co-encapsulated in ZIF-8 with the enzymes together. X-ray diffraction (XRD) analysis indicates the composite possesses the similar crystalline structure with pure ZIF-8. Fluorescence microscope images, Fourier transform infrared spectra and energy dispersive X-ray spectroscopy indicate the presence of AuNCs in the composite. Owing to the high local concentrations of the fluorescent probe and the quenching agent in AuNCs/ß-Gal/GOx@ZIF-8, the quenching rate was enhanced 3.4-fold that of free AuNCs and enzymes in solution.

Facile preparation of hydroxyl bearing covalent organic frameworks for analysis of phenoxy carboxylic acid pesticide residue in plant-derived food.

The development of sensitive method for analysis ofpesticide residue is of great significance to ensure food safety and promote globalization of food trade. An original method was proposed for analysis of phenoxy carboxylic acids (PCAs) pesticide in plant-derived food. To concentrate trace PCAs, the TAPT-DHTA-COF was fabricated by a facile room-temperature method and utilized as the solid phase extraction cartridge packing. The TAPT-DHTA-COF exhibited excellent adsorption capacity and recyclability towards PCAs. Theoretical simulation indicated that the adsorption of PCAs onto the TAPT-DHTA-COF was driven by hydrogen bond, halogen bond and π-π interaction. Using liquid chromatography tandem mass spectrometry for detection, good linearity ranged from 0.10 to 40 ng·g-1 and low limits of detection varied from 0.007 to 0.030 ng·g-1 were achieved for PCAs in rice, apple and greengrocery. The recoveries of PCAs from the spiked samples ranged from 81.2% to 107%. The reliability was verified by the accurate determination of certified reference materials.