METTL3/16-mediated m6A modification of ZNNT1 promotes hepatocellular carcinoma progression by activating ZNNT1/osteopontin/S100A9 positive feedback loop-mediated crosstalk between macrophages and tumour cells.

Macrophages are the major components of tumour microenvironment, which play critical roles in tumour development. N6-methyladenosine (m6A) also contributes to tumour progression. However, the potential roles of m6A in modulating macrophages in hepatocellular carcinoma (HCC) are poorly understood. Here, we identified ZNNT1 as an HCC-related m6A modification target, which was upregulated and associated with poor prognosis of HCC. METTL3 and METTL16-mediated m6A modification contributed to ZNNT1 upregulation through stabilizing ZNNT1 transcript. ZNNT1 exerted oncogenic roles in HCC. Furthermore, ZNNT1 recruited and induced M2 polarization of macrophages via up-regulating osteopontin (OPN) expression and secretion. M2 Macrophages-recruited by ZNNT1-overexpressed HCC cells secreted S100A9, which further upregulated ZNNT1 expression in HCC cells via AGER/NF-κB signaling. Thus, this study demonstrates that m6A modification activated the ZNNT1/OPN/S100A9 positive feedback loop, which promoted macrophages recruitment and M2 polarization, and enhanced malignant features of HCC cells. m6A modification-triggered ZNNT1/OPN/S100A9 feedback loop represents potential therapeutic target for HCC.

CBX2-mediated suppression of SIAH2 triggers WNK1 accumulations to promote glycolysis in hepatocellular carcinoma.

Previous studies have highlighted the poor prognosis of liver cancer, and treatment effects are overall limited. We aimed to confirm the biological roles of SIAH2 in liver cancer and provide potential therapeutic targets. Differential analysis was conducted based on public datasets and found that SIAH2 expressed lowly in HCC samples relative to normal tissues, which was demonstrated in tumor samples via immunohistochemistry (IHC). Besides, SIAH2 overexpression could significantly suppress HCC proliferation. SIAH2 deficiency induced cell proliferation, migration and self-renewal abilities in vitro and in vivo. Mechanistically, SIAH2 could interact with WNK1, and trigger the ubiquitination and degradation of WNK1 proteins. In addition, low SIAH2 depended on elevated WNK1 proteins to drive HCC malignant features, including proliferation, migration and stemness. Meanwhile, we further found that CBX2 could regulate SIAH2 expressions. CBX2 cooperated with EZH2 to mediate the H3K27me3 enrichment on the promoter region of SIAH2 to suppress its transcriptional levels. High CBX2/EZH2 levels in HCC correlated with poor prognosis of patients. Gene set enrichment analysis (GSEA) further implicated that WNK1 correlates tightly with glycolytic process in HCC samples. WNK1 overexpression was found to notably enhance glycolytic activity, whereas WNK1 deficiency could significantly suppress the HCC glycolysis activity. Lastly, the subcutaneous tumor model further demonstrated that targeting WNK1 was effective to inhibit the in vivo tumor growth of SIAH2low HCC. Collectively, down-regulated SIAH2 expressions induced by CBX2/EZH2 could drive progression and glycolysis via accumulating WNK1 proteins, indicating that CBX2/SIAH2/WNK1 axis is a potential prognostic biomarker and therapeutic vulnerability for human HCC.

E3 ubiquitin ligase HECTD3 is a tumor suppressor and mediates the polyubiquitination of SLC7A11 to promote ferroptosis in colon cancer.

Homologous to the E6-associated protein carboxyl terminus domain containing 3 (HECTD3) has been reported to play an essential role in biological processes, including drug resistance, metastasis or apoptosis. However, the relationships between HECTD3 and Colorectal cancer (CRC) remain to be unclear. In this study, we discovered that HECTD3 expressed lowly in CRC compared with normal tissues and patients with low HECTD3 suffered from poorer survival outcomes relative to those with high HECTD3 levels. HECTD3 inhibition could significantly enhance proliferative, clone abilities and self-renewal capacities of CRC cells in vitro and in vivo. Mechanistically, our findings revealed that HECTD3 had endogenous interactions with SLC7A11 proteins. HECTD3 promoted the polyubiquitination of SLC7A11 to trigger the degradation of SLC7A11 proteins. Targeting HECTD3 could notably prolong the half-life period of SLC7A11 proteins, thereby promoting its stability. However, the cysteine mutation at amino acid 823 (ubiquitinase active site) of HECTD3 impaired the polyubiquitination of SLC7A11. HECTD3 deficiency depended on accumulated SLC7A11 proteins to accelerate malignant progression of CRC in vitro and in vivo. Thus, HECTD3 could suppress SLC7A11 levels to attenuate the SLC7A11-mediated cystine uptake, leading to enhanced CRC ferroptosis. SLC7A11 inhibition through polyubiquitination by HECTD3 increased ferroptosis, thereby inhibiting CRC tumor growth. Taken together, these results showed that HECTD3 controlled the stability of SLC7A11 and uncovered the function of HECTD3/SLC7A11 axis in regulating CRC progression.

N6 -methyladenosine-modified FAM111A-DT promotes hepatocellular carcinoma growth via epigenetically activating FAM111A.

As an epitranscriptomic modulation manner, N6 -methyladenosine (m6 A) modification plays important roles in various diseases, including hepatocellular carcinoma (HCC). m6 A modification affects the fate of RNAs. The potential contributions of m6 A to the functions of RNA still need further investigation. In this study, we identified long noncoding RNA FAM111A-DT as an m6 A-modified RNA and confirmed three m6 A sites on FAM111A-DT. The m6 A modification level of FAM111A-DT was increased in HCC tissues and cell lines, and increased m6 A level was correlated with poor survival of HCC patients. m6 A modification increased the stability of FAM111A-DT transcript, whose expression level showed similar clinical relevance to that of the m6 A level of FAM111A-DT. Functional assays found that only m6 A-modified FAM111A-DT promoted HCC cellular proliferation, DNA replication, and HCC tumor growth. Mutation of m6 A sites on FAM111A-DT abolished the roles of FAM111A-DT. Mechanistic investigations found that m6 A-modified FAM111A-DT bound to FAM111A promoter and also interacted with m6 A reader YTHDC1, which further bound and recruited histone demethylase KDM3B to FAM111A promoter, leading to the reduction of the repressive histone mark H3K9me2 and transcriptional activation of FAM111A. The expression of FAM111A was positively correlated with the m6 A level of FAM111A-DT, and the expression of methyltransferase complex, YTHDC1, and KDM3B in HCC tissues. Depletion of FAM111A largely attenuated the roles of m6 A-modified FAM111A-DT in HCC. In summary, the m6 A-modified FAM111A-DT/YTHDC1/KDM3B/FAM111A regulatory axis promoted HCC growth and represented a candidate therapeutic target for HCC.

A mini review of the recent progress of electrode materials for low-temperature solid oxide fuel cells.

Lowering the operating temperature (450-650 °C) of solid oxide fuel cells (SOFCs) faces the intrinsic challenge of sluggish electrode reaction kinetics in the low temperature (LT) range. To accelerate the electrode reaction rate, many efforts have been put into the optimization of electrode composition and morphology. In this review, we have summarized recent developments of LT-SOFC electrodes, including anode and cathode materials. For anode performance improvement, the internal structure design, fine anode structure, reforming layer addition, and in situ exsolution techniques are introduced and their related functionalities are also explained, respectively. While for the cathode, we focus on the perovskite-type materials because of their superior catalytic performance and relatively good stability. The optimization of perovskite composition, including A site alkali or alkali-earth metal doping and B site variable-valence transition metal doping, is discussed in detail based on their effects on oxygen reduction reaction (ORR). Besides, nanostructure assembly and 3D morphology design are also recent hotspots for cathode research. Finally, we also propose several research directions in this field, hoping to provide guidelines for future research.

Enhancement of tolerance against flonicamid in Solenopsis invicta (Hymenoptera: Formicidae) through overexpression of CYP6A14.

Solenopsis invicta is a main issue in southern China and is causing significant damage to the local ecological environment. The extensive use of insecticides has resulted in the development of tolerance in S. invicta. In our study, ten S. invicta colonies from Sichuan Province exhibited varying degrees of tolerance against flonicamid, with LC50 values from 0.49 mg/L to 8.54 mg/L. The sensitivity of S. invicta to flonicamid significantly increased after treatment with the P450 enzyme inhibitor piperonyl butoxide (PBO). Additionally, the activity of P450 in S. invicta was significantly enhanced after being treated with flonicamid. Flonicamid induced the expression levels of CYP4aa1, CYP9e2, CYP4C1, and CYP6A14. The expression levels of these P450 genes were significantly higher in the tolerant colonies compared to the sensitive colonies, and the relative copy numbers of CYP6A14 in the tolerant colonies were 2.01-2.15 fold. RNAi feeding treatment effectively inhibited the expression of P450 genes, thereby reducing the tolerance of S. invicta against flonicamid. In addition, the overexpression of CYP6A14 in D. melanogaster resulted in reduced sensitivity to flonicamid. Our investigations revealed hydrophobic interactions between flonicamid and seven amino acid residues of CYP6A14, along with the formation of a hydrogen bond between Glu306 and flonicamid. Our findings suggest that flonicamid can effectively control S. invicta and P450 plays a pivotal role in the tolerance of S. invicta against flonicamid. The overexpression of CYP6A14 also increased tolerance to flonicamid.

A Systematic Review of Methodological Tools for Evaluating the Water, Energy, Food, and One Health Nexus in Transboundary Water Basins.

Water plays a vital role in human socioeconomic development and overall well-being, making its effective management essential in achieving the Sustainable Development Goals. The close interlinkage between water, other environmental resources, and socioeconomic development have prompted the emergence and adoption of holistic and trans-sectoral concepts such as integrated water resources management and, more recently, the resource nexus. However, even such holistic approaches often exclude the one health approach, particularly at the transboundary water basins (TWBs), which not only dominate 40% of the earth but are vital in environmental and human sustainability. This review aimed to understand, evaluate, and compare assessment tools for water, energy, food, and one health (WEF + H) nexus management in TWBs. The review applied the systematic review guidelines for articles published in the Scopus database. The inclusion criteria encompassed English-language articles featuring case studies, meta-studies, or review articles with no less than three nexus resources. The review categorized the article based on criteria that focused on identifying tools capable of analyzing scenarios and policies for WEF + H in TWBs and their accessibility and easiness of implementation in case studies. Of the eighteen analyzed tools, 13 (72%) had limitations in their application at various geographical scales. Additionally, they could not integrate one health into the nexus or analyze policies through running scenarios. On the contrary, the Bayesian networks, system dynamics, agent-based models, life-cycle assessments, and input-output tools were highly accessible for efficiently conducting scenario-based WEF + H nexus assessments in TWBs.

Status of Fungicide Resistance and Physiological Characterization of Tebuconazole Resistance in Rhizocotonia solani in Sichuan Province, China.

The resistance prevalence of chemical fungicides has caused increasingly serious agro-ecological environmental problems. However, there are few previous reports about resistance to succinate dehydrogenase (SDHI) or sterol demethylation inhibitor (DMI) in Rhizoctonia solani, one of the main agro-diseases. In this study, the fungicide resistance of 122 R. solani isolates in Sichuan Province was monitored by the mycelial growth rate method. Results showed that all isolates were susceptible to hexaconazole and most isolates were susceptible to thifluzamide, except for the field isolate MSRS-2-7 due to a moderate resistance to thifluzamide (16.43-fold resistance ratio, RR), compared to the sensitivity baseline of thifluzamide (0.042 µg/mL EC50 values). On the contrary, many isolates showed moderate or high resistance to tebuconazole (10.59- to 60.78-fold RR), reaching EC50 values of 0.54~3.10 µg/mL, especially for a highly resistant isolate LZHJ-1-8 displaying moderate resistance to epoxiconazole (35.40-fold RR due to a 3.54 µg/mL EC50 value). The fitness determination found that the tebuconazole-resistant isolates showed higher fitness cost with these characteristics, including a lower growth rate, higher relative electric conductivity, an increased ability to tolerate tebuconazole, and high osmotic pressure. Four new mutations of cytochrome P450 sterol 14α-demethylase (CYP51), namely, S94A, N406S, H793R, and L750P, which is the target for DMI fungicides, was found in the tebuconazole-resistant isolates. Furthermore, the lowest binding energy with tebuconazole was also found in the LZHJ-1-8 isolate possessing all the mutations through analyses with Discovery Studio software. Therefore, these new mutation sites of CYP51 may be linked to the resistance against tebuconazole, and its application for controlling R. solani should be restricted in some areas.

An analysis of the correlation between diabetic retinopathy and preretinal oxygen tension using three-dimensional spoiled gradient-recalled echo sequence imaging.

BACKGROUND: The aims of this study were to evaluate the levels of preretinal oxygen tension in patients with diabetes who did not have hypertension by using three-dimensional spoiled gradient-recalled (3D-SPGR) echo sequence imaging and to explore the correlation between diabetic retinopathy (DR) and changes in preretinal oxygen tension. METHOD: This study involved 15 patients with type 2 diabetes without hypertension, who were divided into a diabetic retinopathy (DR) group (n = 10 eyes) and a diabetic non-retinopathy (NDR) group (n = 20 eyes), according to the results of a fundus photography test. Another healthy control group (n = 14 eyes) also participated in the study. The preretinal vitreous optic disc area, nasal side, and temporal side signal intensity of the eyes was assessed before and after oxygen inhalation with the use of 3D-SPGR echo magnetic resonance imaging (MRI). The signal acquisition time was 10, 20, 30, 40, and 50 min after oxygen inhalation. RESULTS: The results showed that, in the DR and NDR groups, the preretinal vitreous oxygen tension increased rapidly at 10 min after oxygen inhalation and peaked at 30-40 min, and the increased slope of the DR group was higher than that of the NDR group. The oxygen tension of the preretinal vitreous gradually increased after oxygen inhalation, and the difference between the DR and NDR groups and the control group was statistically significant (P < 0.05). The preretinal vitreous oxygen tension was higher in the optic disc, temporal side, and nasal side in the NDR group than in the control group, and the difference was statistically significant (P < 0.05). The maximum slope ratios of the optic disc and the temporal side of the DR group were greater than those of the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Three-dimensional-SPGR echo MRI sequencing technology is useful for detecting preretinal oxygen tension levels in patients with diabetes. It can be used as one of the functional and imaging observation indicators for the early diagnosis of DR.

Resistance of Sogatella furcifera to triflumezopyrim mediated with the overexpression of CYPSF01 which was regulated by nuclear receptor USP.

Sogatella furcifera is one of the main agricultural pests in many Asian countries, bringing about enormous injury. A triflumezopyrim-resistant (Tri) strain of S. furcifera was established through continuous screening in laboratory. The determination of synergist and enzyme activity indicated that P450s, especially for the upregulation expression of CYPSF01, played a key role in the increased resistance, confirmed by RNAi, and the recombinant protein of CYPSF01 and NADPH-P450 reductase was able to degrade triflumezopyrim. CYPSF01 had an obviously co-expression relationship with nuclear receptor ultraspiracle (USP), which were all significantly up-regulated when exposed to triflumezopyrim. Further, a USP-binding motif MA0534.1 was enriched from the upregulated peaks by Assay for Transposase Accessible Chromatin (ATAC-seq) analysis, which exited in the peaks located on the promoter of CYPSF01; the yeast one-hybrid experiments confirmed that USP could bind to the CYPSF01 promoter. And the USP interference significantly down-regulated CYPSF01 expression, and resulted in the significantly increasing sensitivity to triflumezopyrim, its mortality rate increased 28.37%. Therefore, the overexpression of USP could cause to the overexpression of CYPSF01, ultimately resulting in the resistance to triflumezopyrim in S. furcifera.

Maf regulates the overexpression of CYP307A1, which is involved in the fitness advantage of bistrifluron-resistant Spodoptera litura (Fab.) (Noctuidae: Lepidoptera).

Spodoptera litura is a widely distributed multifeeding pest, that has developed high resistance to many chemical insecticides. In the present study, a bistrifluron-resistant (Bis-SEL) strain showing 113.8-fold resistance ratio relative to a bistrifluron-susceptible (Bis-UNSEL) strain was obtained and showed a fitness advantage (resurgence). First, we found that the observed resurgence might have resulted from Maf transcription factor overexpression in the Bis-SEL strain, which would influence the synthesis of ecdysone and chitin. Additionally, a co-expression relationship between Maf and CYP307A1 was verified by weighted correlation network analysis (WGCNA) and qRT-PCR, and the expression of CYP307A1, a key gene in ecdysone synthesis, was significantly downregulated by Maf interference. The assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and a yeast one-hybrid showed that Maf could bind to the cncc:maf-s element in the CYP307A1 promoter region. The synthesis of ecdysone, which stimulated chitin synthesis, was also decreased significantly following Maf and CYP307A1 interference. Therefore, the upregulation of Maf expression leaded to the upregulation CYP307A1 expression, which led to an increase in the synthesis of ecdysone, resulting in resurgence accompanied by resistance to bistrifluron.

Differences in susceptibility to chlorantraniliprole between Chilo suppressalis (Lepidoptera: Crambidae) and two dominant parasitic wasps collected from Sichuan Province, China.

Chilo suppressalis Walker (Lepidoptera: Crambidae) is one of the most destructive pests occurring in the rice-growing regions of Asia. Parasitoids, mainly egg parasitoids, have been of interest for several years even with practical used cases. Therefore, the potential impact of insecticides on natural enemies needs great attention. In this study, chlorantraniliprole was evaluated for its impact on C. suppressalis and two dominant parasitic wasps. Bioassays showed that chlorantraniliprole had negligible toxicity to Eriborus terebrans but was significantly toxic to Chelonus munakatae; the mortality exceeded 50% when the concentration reached 46.83 ng/cm2. Enzyme assays suggested that the significantly different carboxylesterase activity may be involved in the high-level detoxification metabolism of E. terebrans. According to the results of enzyme gene correlation analysis, P450s may be the dominant factor in the detoxification metabolism of C. munakatae. In addition, the ryanodine receptor C-terminus of C. suppressalis (CsRyR), C. munakatae (CmRyR) and E. terebrans (EtRyR) were successfully cloned. Different amino acids at resistance mutation I4758 M between susceptible C. suppressalis (I) and parasitic wasps (M) may be related to susceptibility differences. Simulated docking showed that CsRyR and CmRyR can interact with chlorantraniliprole but not EtRyR. More interaction forces were formed between CsRyR and chlorantraniliprole than CmRyR. Furthermore, a Pi-Pi T-shape formed between 73PHE in CsRyR and the benzene ring in chlorantraniliprole. These results indicated that both detoxification metabolism and the target site could mediate the susceptibility difference between C. suppressalis and its parasitic wasps.

Reproductive Outbreaks of Sogatella furcifera Mediated by Overexpression of the Nuclear Receptor USP under Pressure from Triflumezopyrim.

Long-term pesticide-driven selection pressure is one of the main causes of insect outbreaks. In this study, we found that low doses of triflumezopyrim could increase the fecundity of white-backed planthoppers (Sogatella furcifera). By continuously screening 20 generations with a low dose of triflumezopyrim, a triflumezopyrim-resistant strain (Tri-strain, resistance ratio = 20.9-fold) was obtained. The average oviposition quantity and longevity of the Tri-strain (208.77 eggs and 21.31 days, respectively) were significantly higher than those of the susceptible strain (Sus-strain) (164.62 eggs and 17.85 days, respectively). To better understand the mechanism underlying the effects on reproduction, we detected the expression levels of several reproduction-related transcription factors in both the Tri- and Sus-strains. Ultraspiracle (USP) was significantly overexpressed in the Tri-strain. Knockdown of USP by RNAi severely inhibited the moulting process of S. furcifera and disrupted the development of female adult ovaries. Among the potential downstream target genes of USP, Kr-h1 (0.19-fold), Cht8 (0.56-fold) and GPCR A22 (0.31-fold) showed downregulated expression after USP-RNAi. In contrast, the expression of EcR (2.55-fold), which forms heterodimers with USP, was significantly upregulated. Furthermore, RNAi was performed on Kr-h1 in the Tri-strain, and the results show that larval moulting and the development of female adult ovaries were inhibited, consistent with the USP-RNAi results in S. furcifera. These results suggest that the transcription factors USP and Kr-h1 play important roles in the reproductive development of S. furcifera, and overexpression of USP and Kr-h1 in the Tri-resistant strain may result in reproductive outbreaks of pests.

CircCAMSAP1 promotes hepatocellular carcinoma progression through miR-1294/GRAMD1A pathway.

Hepatocellular carcinoma (HCC) is one of the most common cancers with high prevalence and mortality, and it has brought huge economic and health burden for the world. It is urgent to found novel targets for HCC diagnosis and clinical intervention. Circular RNA (circRNA) has been reported to participate in many cancer progressions including HCC, suggesting that circRNA might paly essential role in HCC initiation and progression. Our study aims to found that potential circRNA participates in HCC development and its underlying molecular mechanisms. We obtained three pairs of HCC tissues and its adjacent normal tissues data from GEO DataSets. MTT, cell colony, EdU, wound-healing, transwell invasion and mouse xenograft model assays were used to demonstrate the biological functions of circCAMSAP1 in HCC progression. Furthermore, we conducted bioinformatics analysis, AGO2-RIP, RNA pull-down and luciferase reporter assays to assess the association of circCAMSAP1-miR-1294-GRAMD1A axis in HCC cells. The expression of circCAMSAP1 was up-regulated in HCC tissues compared with its adjacent normal tissues. Up-regulation of circCAMSAP1 promoted HCC biological functions both in vitro and in vivo. The promotive effects of circCAMSAP1 on HCC progression function through miR-1294/GRAMD1A pathway. CircCAMSAP1 was up-regulated in HCC tissues, and circCAMSAP1 up-regulated GRAMD1A expression to promote HCC proliferation, migration and invasion through miR-1294. CircCAMSAP1 might be a potential prognosis and therapeutic target for HCC.

Detection of Rotavirus Vaccine Strains in Oysters and Sewage and Their Relationship with the Gastroenteritis Epidemic.

Rotavirus is one of the major causes of infectious gastroenteritis among infants and children, and live attenuated vaccines for rotavirus A (RVA), namely, Rotarix and RotaTeq, have recently become available in Japan. Rotavirus is known to be excreted from patients and accumulated in oysters similar to norovirus; however, the vaccine strains in aquatic environments or oysters have not yet been analyzed. In this study, we focused on wild-type RVA, which is highly important in considering the risk of infectious diseases. We quantified total RVA, Rotarix, and RotaTeq strains in oyster and sewage samples collected between September 2014 and July 2016 to assess the contamination levels of wild-type RVA by subtracting the quantitative value of rotavirus vaccine strains from that of total RVA. The positive rates of wild-type RVA, Rotarix, and RotaTeq in oysters were 54, 14, and 31%, respectively. These rates were comparable to those of wild-type RVA (57%) and RotaTeq (35%) in sewage; however, Rotarix was not detected in any sewage samples. The comparison of viral concentrations in oysters and sewage suggested more efficient accumulation of the vaccine strains in oysters than the wild-type RVA. The concentration of wild-type RVA in oysters was significantly correlated with that in sewage with a lag time of -6 to 0 weeks which is required for viral transportation from wastewater treatment plants to oysters. On the other hand, no significant correlation was observed between wild-type RVA concentration in sewage and the number of rotavirus-associated gastroenteritis cases, implying the existence of asymptomatic RVA-infected individuals.IMPORTANCE We quantified rotavirus A (RVA), Rotarix, and RotaTeq strains in oyster and sewage samples during two gastroenteritis seasons and revealed the exact contamination of wild-type RVA by subtracting the quantitative value of rotavirus vaccine strains from that of RVA. The concentration of wild-type RVA was significantly correlated between oysters and sewage, although no significant correlation was seen between wild-type RVA concentration in sewage and the number of rotavirus-associated gastroenteritis cases. This finding suggested the existence of asymptomatic patients and that monitoring of rotavirus vaccine strain could be useful to understand the trend of wild-type RVA and rotavirus outbreak in detail. We believe that our study makes a significant contribution to the literature because it reports the detection of rotavirus vaccine strains in oysters.

hsa_circ_0000092 promotes hepatocellular carcinoma progression through up-regulating HN1 expression by binding to microRNA-338-3p.

Circular RNAs (circRNAs) have been identified in diverse cancers for their role in regulating multiple cellular processes by antagonizing microRNAs (miRNAs or miRs). However, the role of circRNA hsa_circ_0000092 in hepatocellular carcinoma (HCC) still remains enigmatic. Therefore, we aimed to investigate the specific mechanism of hsa_circ_0000092 in HCC. Differentially expressed circRNAs associated to HCC were initially analysed. The expression of hsa_circ_0000092, miR-338-3p and HN1 in HCC tissues and cell lines was examined. Next, the interaction among hsa_circ_0000092, miR-338-3p and HN1 was determined by dual-luciferase reporter, RNA pull-down and northern blot assays. Subsequently, a series of mimic, inhibitor or siRNA plasmids were delivered into HCC cells to validate the effects of hsa_circ_0000092, miR-338-3p and HN1 in controlling cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, the role of hsa_circ_0000092 in tumour growth of HCC in vivo was assessed with hsa_circ_0000092 depleted with siRNA. The hsa_circ_0000092/miR-338-3p/HN1 axis was predicted to participate in the development of HCC. hsa_circ_0000092 and HN1 were highly expressed while miR-338-3p was poorly expressed in HCC tissues and cell lines. hsa_circ_0000092 could competitively bind to miR-338-3p to up-regulate HN1 expression. Moreover, depleted hsa_circ_0000092 or elevated miR-338-3p was shown to suppress HCC cell proliferation, migration, invasion and angiogenesis in vitro via down-regulation of HN1. Furthermore, silencing hsa_circ_0000092 was demonstrated to suppress tumour growth in HCC in vivo. The results of this study suggested that hsa_circ_0000092 impaired miR-338-3p-mediated HN1 inhibition to aggravate the development of HCC, indicating that hsa_circ_0000092 is a potential candidate marker and therapeutic target for HCC.

Strategically Constructed Bilayer Tin (IV) Oxide as Electron Transport Layer Boosts Performance and Reduces Hysteresis in Perovskite Solar Cells.

Nanostructured tin (IV) oxide (SnO2 ) is emerging as an ideal inorganic electron transport layer in n-i-p perovskite devices, due to superior electronic and low-temperature processing properties. However, significant differences in current-voltage performance and hysteresis phenomena arise as a result of the chosen fabrication technique. This indicates enormous scope to optimize the electron transport layer (ETL), however, to date the understanding of the origin of these phenomena is lacking. Reported here is a first comparison of two common SnO2 ETLs with contrasting performance and hysteresis phenomena, with an experimental strategy to combine the beneficial properties in a bilayer ETL architecture. In doing so, this is demonstrated to eliminate room-temperature hysteresis while simultaneously attaining impressive power conversion efficiency (PCE) greater than 20%. This approach highlights a new way to design custom ETLs using functional thin-film coatings of nanomaterials with optimized characteristics for stable, efficient, perovskite solar cells.

Artificial Sweeteners in Pig Feed: A Worldwide Survey and Case Study in Pig Farms in Tianjin, China.

Some artificial sweeteners (ASs) are used in pig feeds, although little is known on this regard. An investigation was conducted by determining seven common ASs in pig feed, manure, wastewater, compost, and soil from 16 pig farms in Tianjin, China. Saccharin (SAC) was predominant in feed (1.41-326 mg/kg) and manure samples (1.06-401 mg/kg). The annual mass loads of ASs in pig feeds were estimated at 5.69-119, 4.92-149, and 1.29-35 kg per 103 piglets, hogs, and sows, respectively. The annual emission of ASs via biowaste (i.e., manure) was estimated at 3.58-85.2, 0.04-26.2, and 0.08-9.97 kg per 103 capita for the three dominant ASs, i.e., SAC, neotame (NEO), and cyclamate (CYC). On a global scale, SAC was also widely detected at concentrations of 0.01-326 mg/kg in pig feed from China, Switzerland, Japan, Chile, and the United States, suggesting the worldwide use of ASs in pig feed. NEO and CYC were found in 41% and 30% of the feed samples, respectively, at concentrations of 0.05-70 mg/kg, whereas other ASs were barely found with rather lower concentrations. The annual mass loads of ASs consumed via pig feed consumption were estimated at 2400 tons worldwide. Thus, pig farming is an important source of ASs to the environment.

Impacts of Manures and Manure-Based Composts on Root Lesion Nematodes and Verticillium dahliae in Michigan Potatoes.

The interaction of the root lesion nematode Pratylenchus penetrans and the fungal plant pathogen Verticillium dahliae causes potato early die (PED) complex, which induces premature vine senescence and dramatically reduces yield in potatoes. Management of PED is often achieved through the use of soil fumigants and nematicides, but their adverse effects on soil, human and environmental health, and strict regulations worldwide require alternative control tactics. In this study, we investigated the effects of multiple composts and manures on nematode mortality and PED. In lab assays, root lesion nematodes were exposed to poultry manure, layer ash blend, Dairy Doo, or wood ash for 7 days at rates of 0, 0.1, 1, 10, and 20% by volume of product and assessed for nematode survivorship. Additionally, these products were evaluated for volatile fatty acid content to determine if fatty acid content affects nematode control. In a field trial, the composts and manures were evaluated at two different rates, high (11.2 t/ha) or low (2.8 t/ha), and populations of P. penetrans and V. dahliae were quantified. Our results show that a 1% application rate of poultry manure and layer ash blend provided the greatest nematode control in lab assays with 24.5 and 38.2% reduction, respectively, with greater control at higher rates. In the field, plots treated with poultry manure had significantly higher potato yields and significantly fewer nematodes than control plots. Taken together, our results suggest that poultry manure could be a promising amendment to control PED.

Benzotriazole alleviates copper mediated lysosomal membrane damage and antioxidant defense system responses in earthworms (Eisenia fetida).

Benzotriazole (BTR) is a common corrosion inhibitor used to protect copper (Cu) and Cu alloys. To reveal the combined subacute toxicity of BTR and Cu at environmental levels on terrestrial animals, the activity of antioxidative enzymes and the glutathione levels in earthworms (Eisenia fetida) of the single or co-exposure treatments were determined. The activity of both antioxidant enzymes and non-enzymatic antioxidants was affected by BTR in earthworms. Moreover, the analyses of lysosomal neutral red retention time and total antioxidant capacity indicated a detoxification effect of BTR on Cu-induced impairments of the antioxidant defense capacity in earthworms. The apoptotic rate of coelomocytes in earthworms of the co-exposure treatment was lower than that in earthworms treated with Cu only, indicating that BTR alleviates Cu mediated lysosomal membrane damage and antioxidant defense system responses in earthworms.