SAD2 functions in plant pathogen Pseudomonas syringae pv tomato DC3000 defense by regulating the nuclear accumulation of MYB30 in Arabidopsis thaliana.

Accurate nucleocytoplasmic transport of signal molecules is essential for plant growth and development. Multiple studies have confirmed that nucleocytoplasmic transport and receptors are involved in regulating plant disease resistance responses, however, little is known about the regulatory mechanism in plants. In this study, we showed that the mutant of the importin beta-like protein SAD2 exhibited a more susceptible phenotype than wild-type Col-0 after treatment with Pseudomonas syringae pv tomato DC3000 (Pst DC3000). Coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) experiments demonstrated that SAD2 interacts with the hypersensitive response (HR)-positive transcriptional regulator MYB30. Subcellular localization showed that MYB30 was not fully localized in the nucleus in sad2-5 mutants, and western-blot experiments further indicated that SAD2 was required for MYB30 nuclear trafficking during the pathogen infection process. A phenotypic test of pathogen inoculation demonstrated that MYB30 partially rescued the disease symptoms of sad2-5 caused by Pst DC3000, and that MYB30 worked downstream of SAD2 in plant pathogen defense. These results suggested that SAD2 might be involved in plant pathogen defense by mediating MYB30 nuclear trafficking. Taken together, our results revealed the important function of SAD2 in plant pathogen defense and enriched understanding of the mechanism of nucleocytoplasmic transport-mediated plant pathogen defense.

Comprehensive exploration of the anaerobic biotransformation of polychlorinated biphenyls in Dehalococcoides mccartyi CG1: Kinetics, enantioselectivity, and isotope fractionation.

Anaerobic microbial transformation is a key pathway in the natural attenuation of polychlorinated biphenyls (PCBs). Much less is known about the transformation behaviors induced by pure organohalide-respiring bacteria, especially kinetic isotope effects. Therefore, the kinetics, pathways, enantioselectivity, and carbon and chlorine isotope fractionation of PCBs transformation by Dehalococcoides mccartyi CG1 were comprehensively explored. The results indicated that the PCBs were mainly dechlorinated via removing their double-flanked meta-chlorine, with their first-order kinetic constants following the order of PCB132 > PCB174 > PCB85 > PCB183 > PCB138. However, PCBs occurred great loss of stoichiometric mass balance during microbial transformation, suggesting the generation of other non-dehalogenation products and/or stable intermediates. The preferential transformation of (-)-atropisomers and generation of (+)-atropisomers were observed during PCB132 and PCB174 biotransformation with the enantiomeric enrichment factors of -0.8609 ± 0.1077 and -0.4503 ± 0.1334 (first half incubation times)/-0.1888 ± 0.1354 (second half incubation times), respectively, whereas no enantioselectivity occurred during PCB183 biotransformation. More importantly, although there was no carbon and chlorine isotope fractionation occurring for studied substrates, the δ13C values of dechlorination products, including PCB47 (-28.15 ± 0.35‰ âˆ¼ -27.77 ± 0.20‰), PCB91 (-36.36 ± 0.09‰ âˆ¼ -34.71 ± 0.49‰), and PCB149 (-28.08 ± 0.26‰ âˆ¼ -26.83 ± 0.10‰), were all significantly different from those of their corresponding substrates (PCB85: -30.81 ± 0.02‰ âˆ¼ -30.22 ± 0.21‰, PCB132: -33.57 ± 0.15‰ âˆ¼ -33.13 ± 0.14‰, and PCB174: -26.30 ± 0.09‰ âˆ¼ -26.01 ± 0.07‰), which further supported the generation of other non-dehalogenation products and/or stable intermediates with enrichment or depletion of 13C. These findings provide deeper insights into the anaerobic microbial transformation behaviors of PCBs.

Erratum: A CRISPR Interference of CBP and p300 Selectively Induced Synthetic Lethality in Bladder Cancer Cells In Vitro: Erratum.

[This corrects the article DOI: 10.7150/ijbs.32332.].

Higher concentration of P7C3 than required for neuroprotection suppresses renal cell carcinoma growth and metastasis.

Background: P7C3 is a novel compound that has been widely applied in neurodegenerative diseases and nerve injury repair. Here, we show that higher concentrations of P7C3 than are required for in vivo neuroprotection have the novel function of suppressing renal cell carcinoma (RCC) proliferation and metastasis. Methods: Colony formation, CCK-8 and EdU assay were applied to evaluate RCC cell proliferation. Wound healing and transwell assay were used to measure RCC cell migration and invasion. Flow cytometry assay was employed to detect RCC cell apoptosis and cell cycle. qRT-PCR assay was carried out to measure ribonucleotide reductase subunit M2 (RRM2) mRNA expression level, while western blot assay was utilized to detect the expression level of target proteins. RCC cell growth in vivo was determined by xenografts in mice. Results: We observed that high concentrations of P7C3 could restrain the proliferation and metastasis of RCC cells and promote cell apoptosis. Mechanistically, this new effect of higher dose of P7C3 was associated with reduced expression of RRM2, and the beneficial efficacy of P7C3 in RCC was blocked when suppression of RRM2 was prevented. When RRM2 suppression was permitted, the cGAS-STING pathway was activated by virtue of RRM2/Bcl-2/Bax signaling. Lastly, intraperitoneal injection of this high level of P7C3 in mice potently inhibited tumor growth. Conclusion: In conclusion, we show here that P7C3 that exerts an anti-cancer effect in RCC. Our study indicated that P7C3 might act as a novel drug for RCC in the future. The regulatory signal pathway RRM2/Bcl-2/BAX/cGAS-STING might present novel insight to the potential mechanism of RCC development.

Occurrence, composition, and spatial distribution of dechlorane plus in surface sediments of black-odorous urban rivers across China.

China, one of the two dechlorane plus (DP) producers, might have become a major area of DP pollution. The environmental contamination status of DP in sediments across the whole of China has not yet been studied. In the current study, the pollution levels, spatial distribution, and compositions of DP were investigated comprehensively in surface sediments from 173 black-odorous urban rivers across China for the first time. Total DP concentrations varied from not-detected to 39.71 ng/g dw, with an average concentration of 3.20 ± 4.74 ng/g dw, which was polluted by local emission sources and presented significant differences among different sampling cities. Among the seven administrative regions of China, DP concentrations were the highest in South China and showed a decreasing trend from southeastern coastal areas to northwest inland regions. Spearman's correlation analysis suggested that the gross industrial output, gross domestic product, and daily wastewater treatment capacity were not the principal factors controlling the spatial distribution of DP. The fanti values (the concentration ratios of anti-DP to the sum of anti-DP and syn-DP) varied from 0.19 to 0.88, with those in most sediments falling in the range of DP technical product (0.60 ~ 0.80), suggesting no apparent stereoselective enrichment occurred. Moreover, the anti-Cl11-DP was detected in sediments (n.d. ~ 0.40 ng/g dw), which showed significantly and insignificantly positive correlation with the anti-DP levels and fanti, respectively, implying it might mainly originate from the byproduct of DP technical product rather than the dechlorination of anti-DP.

Insights into the occurrence, spatial distribution, and ecological implications of organophosphate triesters in surface sediments from polluted urban rivers across China.

Organophosphate triesters (tri-OPEs) are a kind of widespread contaminants in the world, particularly in China, which is a major producer and user of tri-OPEs. However, tri-OPE pollution in urban river sediments in China remains unclear. In current work, we carried out the first nationwide investigation to comprehensively monitor 10 conventional and five emerging tri-OPEs in sediments of 173 black-odorous urban rivers throughout China. Concentrations of 10 conventional and five emerging tri-OPEs were 3.8-1240 ng/g dw (mean: 253 ng/g dw) and 0.21-1107 ng/g dw (68 ng/g dw), respectively, and significantly differed among the cities sampled but generally decreased from Northeast and East China to Central and West China. These spatial patterns suggest that tri-OPE pollution was mainly from local sources and was controlled by the industrial and economic development levels in these four areas, as indicated by the significant correlations between tri-OPE concentrations and gross domestic production, gross industrial output, and daily wastewater treatment capacity. Although the tri-OPE composition varied spatially at different sites, which indicated different tri-OPE input patterns, it was commonly dominated by tris(2-chloroethyl) phosphate, tris(2-ethylhexyl) phosphate, and tris(1-chloro-2-propyl) phosphate (conventional tri-OPEs) and bisphenol A-bis(diphenyl phosphate) and isodecyl diphenyl phosphate (emerging tri-OPEs). A risk assessment indicated that tri-OPEs in most sampling sediments had a low to moderate risk to aquatic organisms.

Historical Occurrence and Composition of Novel Brominated Flame Retardants and Dechlorane Plus in Sediments from an Electronic Waste Recycling Site in South China.

Novel brominated flame retardants (NBFRs) and dechlorane plus (DP) have been widely used as alternatives to traditional BFRs. However, little is known about the temporal trends of NBFR and DP pollution in e-waste recycling sites. In the current study, three composite sediment cores were collected from an e-waste-polluted pond located in a typical e-waste recycling site in South China to investigate the historical occurrence and composition of NBFRs and DP. The NBFRs and DP were detected in all layers of the sediment cores with concentration ranges of 5.71~180,895 and 4.95~109,847 ng/g dw, respectively. Except for 2,3,5,6-tetrabromo-p-xylene (pTBX) and 2,3,4,5,6-pentabromoethylbenzene (PBEB), all the NBFR compounds and DP showed a clear increasing trend from the bottom to top layers. These results implied the long-term and severe contamination of NBFRs and DP. Decabromodiphenyl ethane (DBDPE) was the most abundant NBFR with the contribution proportions of 58 ± 15%, 73 ± 15%, and 71 ± 18% in three sediment cores, followed by 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) and pentabromobenzene (HBB). The ratios of BTBPE/Octa-BDEs and DBDPE/Deca-BDEs varied from 0.12 to 60 and from 0.03 to 0.49, respectively, which had no clear increase trends with a decrease in sediment depth. As for DP, the fanti values (the concentration ratios of anti-DP to the sum of anti-DP and syn-DP) in sediment cores ranged from 0.41 to 0.83, almost falling in the range of those in DP technical products, suggesting that DP degradation did not occur in sediment cores. The environmental burdens of DBDPE, BTBPE, HBB, PBT, PBEB, pTBX, and DP were estimated to be 34.0, 5.67, 10.1, 0.02, 0.02, 0.01, and 34.8 kg, respectively. This work provides the first insight into the historical contamination status of NBFRs and DP in the sediments of an e-waste recycling site.

Spatial distribution, conversion, and ecological risk assessment of hexabromocyclododecanes in the sediments of black-odorous urban rivers nationwide in China.

Hexabromocyclododecanes (HBCDs) have become a global pollution problem, particularly in China-a major producer and user of HBCDs. However, little is known about the HBCD pollution status in urban rivers nationwide in China. In this study, we comprehensively investigated the pollution characteristics of HBCDs in 173 sediment samples from black-odorous urban rivers across China. Total HBCD concentrations ranged from not-detected to 848 ng/g dw, showing significant differences among the various sampling cities, but generally increasing from west to east China. This distribution pattern of HBCDs was strongly associated with the local industrial output, gross domestic product, and daily wastewater treatment capacity. α-HBCD was the predominant diastereoisomer in most sediments, with an average proportion of 63.8 ± 18.8 %, followed by γ-HBCD (23.8 ± 19.5 %) and ß-HBCD (12.4 ± 6.49 %), showing a significant increase of the α-HBCD proportions relative to those in HBCD commercial mixtures and an opposite trend for that of γ-HBCD. These results suggested that HBCDs might undergo isomerization from γ- to α-HBCD and biotic/abiotic degradation with preference for γ-HBCD. Of these conversions, the microbial degradation of HBCDs was further verified by the preferential transformation of (-)-α-, (+)-ß-, and (-)-γ-HBCDs and the detection of HBCD-degrading bacteria, including Dehalococcoides, Bacillus, Sphingobium, and Pseudomonas. A risk assessment indicated that HBCDs pose low to moderate risks to aquatic organisms in most black-odorous urban river sediments.

Inhibiting CBP Decreases AR Expression and Inhibits Proliferation in Benign Prostate Epithelial Cells.

(1) Background: CREB-binding protein (CBP) is a key transcriptional coactivator of androgen receptors (AR). We conducted this study to investigate the effects of CBP on AR expression and proliferation in benign prostatic hyperplasia (BPH) prostate epithelial cells. (2) Methods: By analyzing a published data set, we found that CBP was closely related to the gene expression of AR in prostate cells. We enrolled 20 BPH patients who underwent transurethral resection of the prostate (TURP) in Peking University First Hospital in 2022, and analyzed the expressions of CBP and AR in BPH prostate tissues. Then, we used ICG-001 and shRNA to inhibit CBP in prostate epithelial cells (BPH-1 cells and RWPE-1 cells), and conducted immunofluorescence, cell viability assay, flow cytometry analysis, and Western blot to analyze the effects of CBP on AR expression and proliferation in prostate epithelial cells. We also studied the interaction between CBP and AR through a co-immunoprecipitation assay. (3) Results: CBP is consistent with AR in expression intensity in prostate tissues. Inhibiting CBP decreases AR expression, and induces proliferation inhibition, apoptosis, and cell cycle arrest in BPH prostate epithelial cells. The co-immunoprecipitation assay showed that CBP binds with AR to form transcription complexes in prostate epithelial cells. (4) Conclusions: Inhibiting CBP decreases AR expression and inhibits proliferation in benign prostate epithelial cells. CBP may be a potential target to affect AR expression and the proliferation of prostate epithelial cells in BPH.

Sexual dimorphic distribution of G protein-coupled receptor 30 in pain-related regions of the mouse brain.

Sex differences in pain sensitivity have contributed to the fact that medications for curing chronic pain are unsatisfactory. However, the underlying mechanism remains to be elucidated. Brain-derived estrogen participates in modulation of sex differences in pain and related emotion. G protein-coupled receptor 30 (GPR30), identified as a novel estrogen receptor with a different distribution than traditional receptors, has been proved to play a vital role in regulating pain affected by estrogen. However, the contribution of its distribution to sexually dimorphic pain-related behaviors has not been fully explored. In the current study, immunofluorescence assays were applied to mark the neurons expressing GPR30 in male and female mice (in metestrus and proestrus phase) in pain-related brain regions. The neurons that express CaMKIIα or VGAT were also labeled to observe overlap with GPR30. We found that females had more GPR30-positive (GPR30+ ) neurons in the primary somatosensory (S1) and insular cortex (IC) than males. In the lateral habenula (LHb) and the nucleus tractus solitarius (NTS), males had more GPR30+ neurons than females. Moreover, within the LHb, the expression of GPR30 varied with estrous cycle phase; females in metestrus had fewer GPR30+ neurons than those in proestrus. In addition, females had more GPR30+ neurons, which co-expressed CaMKIIα in the medial preoptic nucleus (mPOA) than males, while males had more than females in the basolateral complex of the amygdala (BLA). These findings may partly explain the different modulatory effects of GPR30 in pain and related emotional phenotypes between sexes and provide a basis for comprehension of sexual dimorphism in pain related to estrogen and GPR30, and finally provide new targets for exploiting new treatments of sex-specific pain.

GSH/pH dual response drug delivery system for photothermal enhanced gene-immunotherapy.

Breast cancer has emerged as a leading cause of mortality among women. Photothermal therapy represents a recent therapeutic modality for eradicating localized tumors, albeit hindered by its limited penetration into tumor tissues. Recognizing the potential of photothermal therapy to induce immunogenic cell death in tumor cells, we explored a gene delivery approach utilizing small interfering RNA targeting programmed death ligand 1 (PD-L1), abbreviated as siPD-L1, to bolster the anti-tumor immune response elicited by this therapy. Nonetheless, the suboptimal release efficiency and inherent instability of RNA molecules have posed challenges to their therapeutic efficacy. In this study, we designed a glutathione (GSH)/pH-responsive micelle system, employing biocompatible and low-toxicity polyethyleneimine in conjunction with structurally robust pluronic P123, to encapsulate both indocyanine green (ICG) and siPD-L1 for precise targeting in breast cancer treatment. The resulting PSP/ICG/siPD-L1 nanocarrier demonstrated admirable biocompatibility and stability. Upon internalization into tumor cells, this nanocarrier exhibited rapid release of both ICG and siPD-L1, responding to the acidic tumor microenvironment and GSH conditions. The inclusion of siPD-L1 effectively downregulated the expression of PD-L1 on the tumor cell surface, thereby impeding tumor growth. Additionally, ICG demonstrated a photothermal effect when exposed to near-infrared light. Both in vitro and in vivo investigations substantiated the nanocarrier's efficacy against tumor cells, culminating in the complete ablation of 4T1 tumors in situ. Consequently, PSP/ICG/siPD-L1 emerges as a promising nanocarrier candidate for augmenting anti-tumor immunity through the synergistic combination of photothermal therapy and gene-based intervention.

Anaerobic biotransformation of two novel brominated flame retardants: Kinetics, isotope fractionation and reaction mechanisms.

1,2,5,6-tetrabromocyclooctane (TBCO) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE), as safer alternatives to traditional brominated flame retardants, have been extensively detected in various environmental media and pose emerging risks. However, much less is known about their fate in the environment. Anaerobic microbial transformation is a key pathway for the natural attenuation of contaminants. This study investigated, for the first time, the microbial transformation behaviors of ß-TBCO and DPTE by Dehalococcoides mccartyi strain CG1. The results indicated that both ß-TBCO and DPTE could be easily transformed by D. mccartyi CG1 with kobs values of 0.0218 ± 0.0015 h-1 and 0.0089 ± 0.0003 h-1, respectively. In particular, ß-TBCO seemed to undergo dibromo-elimination and then epoxidation to form 4,5-dibromo-9-oxabicyclo[6.1.0]nonane, while DPTE experienced debromination at the benzene ring (ortho-bromine being removed prior to para-bromine) rather than at the carbon chain. Additionally, pronounced carbon and bromine isotope fractionations were observed during biotransformation of ß-TBCO and DPTE, suggesting that C-Br bond breaking is the rate-limiting step of their biotransformation. Finally, coupled with identified products and isotope fractionation patterns, ß-elimination (E2) and Sn2-nucleophilic substitution were considered the most likely microbial transformation mechanisms for ß-TBCO and DPTE, respectively. This work provides important information for assessing the potential of natural attenuation and environmental risks of ß-TBCO and DPTE.

Dietary berberine against intestinal oxidative stress, inflammation response, and microbiota disturbance caused by chronic copper exposure in freshwater grouper (Acrossocheilus fasciatus).

Berberine (BBR) is known for its strong antioxidant, anti-inflammatory, and capacity to preserve intestinal microbiota balance in fish. This study aimed to investigate the protective effects of berberine against copper-induced toxicity in the intestine of freshwater grouper Acrossocheilus fasciatus. The experiment involved four groups: a control group, a Cu group exposed to 0.02 mg/L Cu2+, and two BBR groups fed with 100 or 400 mg/kg of berberine diets and exposed to the same Cu2+ concentration. Three replicates of healthy fish (initial weight 1.56 ± 0.10 g) were subjected to their respective treatments for 30 days. Results showed that none of the treatments significantly affected the survival rate, final weight, weight gain, and feed intake (P > 0.05). However, supplementation with 100 and 400 mg/kg of BBR significantly lowered the antioxidant activities, and glutathione peroxidase (gpx) and superoxide dismutase (sod) expression levels, as well as reduced malondialdehyde (MDA) content caused by Cu2+ exposure (P < 0.05). Berberine inclusion significantly downregulated proinflammatory factors NLR family pyrin domain containing 3 (nlrp3), interleukin 1 beta (il1ß), interleukin 6 cytokine family signal transducer (il6st) but upregulated transforming growth factor beta 1 (tgfß1) and heat shock 70 kDa protein (hsp70) expression. Moreover, berberine at both levels maintained the intestinal structural integrity and significantly improved gap junction gamma-1 (gjc1) mRNA level compared to the Cu group (P < 0.05). Based on 16S rDNA sequencing, the richness and diversity of intestinal microbiota in different groups were not significantly influenced. Berberine reduced the Firmicutes/Bacteroidota ratio and stifled the growth of some specific pathogenic bacteria such as Pseudomonas, Citrobacter, and Acinetobacter, while boosting the richness of potential probiotic bacteria, including Roseomonas and Reyranella compared with the Cu group. In conclusion, berberine showed significant protective effects against Cu2+-induced intestinal oxidative stress, inflammation response, and microbiota disturbance in freshwater grouper.

Future directions in imaging pouches.

The sections of this special issue on the ileal pouch demonstrate that in the nearly 45 years since the ileal pouch has been utilized to treat patients with colitis and familial adenomatous polyposis, a substantial number of patients experience both short- and long-term morbidity and that imaging plays an important role in their management. Further, referral centers are encountering an increasing number of patients with pouch and peri-pouch complications and dysfunction. Many of these patients have had their pouches for years, and many have experienced a reduced quality of life as a result of their symptoms.As we look to the future, what are the specific questions that arise from this compilation of experience from institutions that see large numbers of patients with an ileal pouch? In what areas are we deficient? In what areas are we using the wrong methods? What should we be doing differently?

Private placements of equity and accessibility of bank loans.

This study investigates the changes in quantity and cost of bank loans after a private placement of common stocks by A-share listed companies in China from 2011 to 2021. This research is derived from the signaling theory and is based on a difference-in-difference design. Through propensity score matching, the sample comprises companies that placed equity privately in the experiment group and companies that did not place equity privately in the control group. We find evidence that the increase in bank loans slowed down, and the cost of bank loans increased after the private placement. The signaling effect of private placements is robust to various additional tests. Further analysis indicates that when state-owned enterprises place equity privately, their access to bank loans is not affected. When institutional investors participate in the private placement, the company's access to bank credit does not go through significant changes. In addition, private placements by companies located in regions with higher levels of marketization of the financial market do not reduce the cost of bank loans.

Occurrence, spatial distribution, and risk assessment of short- and medium-chain chlorinated paraffins in sediment from black-odorous rivers across China.

Chlorinated paraffins (CPs) were massively produced for varied industrial purposes, of which improper handling and consequent environmental release resulted in worldwide contamination. The present study investigated the occurrence and spatial distribution of short- and medium-chain chlorinated paraffins (SCCP/MCCPs) in 171 sediment samples from black-odorous urban rivers across China. Total SCCP and MCCP concentrations ranged from 8.3 to 9.4 × 104 (median: 1.1 × 103) ng/g dw, and from not-detected-value to 1.0 × 106 (median: 1.3 × 104) ng/g dw, respectively. No clear spatial distribution of SCCPs and MCCPs was observed since black-odorous urban rivers were polluted by point-sources of the SCCP/MCCPs. Significant positive correlations were identified between SCCP/MCCPs and total organic carbon, and between SCCP/MCCPs and other persistent organic matter, including polybrominated diethyl ethers, polychlorinated biphenyls, antibiotics, and plasticizers. The average ratios of MCCPs to SCCPs in most samples were divided into 11 and 16, implying the manufacturing and use of at least two types of CP technical mixtures in China. The composition of SCCP/MCCPs were similar to that in their commercial products. Ecological risk assessments by two approaches, including the Federal Environmental Quality Guidelines and Risk Quotient, both revealed that SCCP/MCCP in surface sediments confer an ecological risk. ENVIRONMENTAL IMPLICATION: SCCPs and MCCPs can be considered "hazardous materials" because of their massive production and their potential persistence, long-distance transfer, bioaccumulation potential, and toxicity. This research conducted a comprehensive study on SCCP/MCCP in black-odorous urban river sediments across China and revealed their environmental risk, which may improve understanding of SCCP/MCCP contamination characteristics.

Cryptocaryone induces apoptosis in human hepatocellular carcinoma cells by inhibiting aerobic glycolysis through Akt and c-Src signaling pathways.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with the second highest mortality rate in all cancer. Energy reprogramming is one of the hallmarks of cancer, and emerging evidence showed that targeting glycolysis is a promising strategy for HCC treatment. Cryptocaryone has been shown to display promising anti-cancer activity against numerous types of cancer. Previous study also indicated that cryptocaryone induces cytotoxicity by inhibiting glucose transport in cancer cells, but the detailed mechanism still needs to be elucidated. Therefore, this study aimed to investigate the relationship between the anti-cancer effect and glycolytic metabolism of cryptocaryone in human HCC cells. In this study, we found that cryptocaryone potently induced growth inhibition by apoptotic cell death in HCC cells. Cryptocaryone also suppressed the ATP synthesis, lactate production and glycolytic capacity of HCC cells. Mechanistic investigations showed that phosphorylation of Akt and c-Src, as well as the expression of HK1 were impeded by cryptocaryone. Moreover, cryptocaryone markedly increased the expression level of transcription factor FoxO1. Importantly, clinical database analysis confirmed the negative correlation between HK1 and FoxO1. High expression levels of HK-1 were positively correlated with poorer survival in patients with HCCs. These results suggest that cryptocaryone may promote cell apoptosis by inhibiting FoxO1-mediated aerobic glycolysis through Akt and c-Src signaling cascades in human HCC cells. This is the first study to indicate that cryptocaryone exerts anti-cancer property against human HCC cells. Cryptocaryone is a potential natural product worthy of further development into a promising candidate for HCC treatment.

HOXA1 promotes proliferation and metastasis of bladder cancer by enhancing SMAD3 transcription.

BACKGROUND: Recent studies showed that HOXA1 can promote or suppress the transcription of target genes via binding to their promoter region, therefore regulating the development and progression of various cancers. However, the biological function of HOXA1 in bladder cancer (Bca) remains unknown. METHODS: qRT-PCR and Western blot assay was performed to measure the mRNA protein level of HOXA1 in Bca cells. CCK-8 and cell colony formation assay were carried out to detect cell proliferation ability. Wound healing assay was applied to detect cell migration ability, while transwell assay was applied to detect cell invasion ability. Chromatin Immunoprecipitation (ChIP) and dual-luciferase reporter assay were used to investigate the molecular mechanisms underlying HOXA1. RESULTS: In this study, we discovered that HOXA1 mRNA and protein was dramatically increased in Bca tissues and cells compared to matched normal tissues and normal bladder epithelial cell. Enhanced HOXA1 expression was positively correlated with bigger tumor size and lymphatic metastasis, causing shorter overall survival to Bca patients. Knockdown of HOXA1 obviously impaired cell proliferation and metastasis ability. Further experiments proved that HOXA1 could strength the transcription of SMAD3 via binding to the promoter region of SMAD3. CONCLUSION: In conclusion, our study suggested that HOXA1 contributed to the growth and metastasis of Bca and it might serve as a tumor biomarker for Bca treatment and prognosis monitoring.

Nontarget analysis and comprehensive characterization of halogenated organic pollutants by GC-Q-Orbitrap-HRMS in association with chromatogram segmentation and Cl/Br-specific screening algorithms.

Nontarget analysis enables high-efficiency screening and identification of halogenated organic pollutants (HOPs) in complex matrices irrespective of lacking authentic standards, particularly for novel and emerging species, thereby realizing comprehensive component characterization of HOPs. Notwithstanding, nontarget analysis and comprehensive characterization of HOPs remain on the way to improvement. In this study, we implemented nontarget analysis of HOPs in fly ash, egg and sediment using gas chromatography quadrupole-orbitrap high-resolution mass spectrometry with the aid of chromatogram segmentation and Cl/Br-specific screening algorithms, and further performed comprehensive characterization of components and distribution of HOPs. In total, 122 HOP formulas were identified and tentatively assigned with structures, of which 28 were found in ≥ two matrices. Taking isomers into account, in total 1059 HOP congeners were found. Based on the identification and semiquantification results, the chemical components and concentration profiles of HOPs were preliminarily clarified, and accordingly the overall pollution signatures of HOPs were sketched. The total concentrations of HOPs in the fly ash, egg and sediment were 4.7, 41.2 and 750.8 µg g-1, respectively. Organochlorines were the most abundant among the categories classified by halogen types, and halogenated benzenes, halogenated dioxins, halogenated biphenyls/terphenyls and halogenated polycyclic aromatic hydrocarbons (H-PAHs) were the predominant of the structurally classified categories. Moreover, dozens of formulas of novel/little-known HOPs such as mix-chlorinated/brominated PAHs with ≥4 aromatic rings and polychlorinated terphenyls were identified. This study presents an accurate and high-performance nontarget analysis method for HOPs in complex matrices, and yields new cognitions on the pollution status of HOPs from an overall perspective.