Insights into the low-temperature rapid catalytic pyrolysis and remediation mechanism of weathered petroleum-contaminated saline-alkali soil using Beta zeolite.

Pyrolysis technique is considered to have great potential in the remediation of petroleum-contaminated soil, but it still has difficulties such as high energy consumption for the degradation of complex petroleum hydrocarbons and the deterioration of soil quality after treatment. In this study, the low-temperature rapid catalytic pyrolysis was realized using Beta zeolite to assist in remediating weathered petroleum-contaminated saline-alkali soil. Under the action of Beta zeolite, the removal efficiency of petroleum hydrocarbons reached 81% after pyrolysis treatment for 10 min at 250 °C, which was reduced to regulatory standard. The pyrolysis behavior and mechanism revealed that the addition of Beta zeolite effectively reduced the activation energy of C-C and C-O bonds cleavage in petroleum hydrocarbon macromolecules due to the strong acidity of Beta, meanwhile the quality of recovered oil from pyrolysis was improved. Additionally, the analyses of soil physicochemical property indicated that the harmless graphitic C generated from the degradation of petroleum hydrocarbons increased the organic matter in the soil, and the addition of Beta zeolite enhanced soil water retention capacity and reduced the soil alkalinity, thus improving the ecological function of saline-alkali soil. This study provides a new strategy for the removal of organic pollutants under special soil media conditions.

Long-term effect of phenol, quinoline, and pyridine on nitrite accumulation in the nitrification process: performance, microbial community, metagenomics and molecular docking analysis.

Phenol, quinoline, and pyridine, commonly found in industrial wastewater, disrupt the nitrification process, leading to nitrite accumulation. This study explores the potential mechanisms through which these biotoxic organic compounds affect nitrite accumulation, using metagenomic and molecular docking analyses. Despite increasing concentrations of these compounds from 40 to 160 mg/L, ammonia nitrogen removal was not hindered, and stable nitrite accumulation rates exceeding 90 % were maintained. Additionally, these compounds inhibited nitrite-oxidizing bacteria (NOB) and enriched ammonia-oxidizing bacteria (AOB) in situ. As the concentration of these compounds rose, protein (PN) and polysaccharide (PS) concentrations also increased, along with a higher PN/PS ratio. Metagenomic analysis further revealed an increase in hao relative abundance, while microbial community analysis showed increased Nitrosomonas abundance, which contributed to nitrite accumulation stability. Molecular docking indicated that these compounds have lower binding energy with hydroxylamine oxidoreductase (HAO) and nitrate reductase (NAR), theoretically supporting the observed sustained nitrite accumulation.

Pixel-based small-window parametric ultrasound imaging for liver tumor characterization.

Purpose: Characterizing liver tumors remains a challenge in clinical practice. Ultrasound parametric imaging based on statistical distribution can enhance image contrast compared with B-mode imaging, requiring scatterers following specific distributions. This study proposes a pixel-based small-window parametric ultrasound imaging method using weighted horizontally normalized Shannon entropy (WhNSE) and fuzzy entropy (FE) to improve detectability liver tumor. Methods: Pixel-based parametric imaging requires a sliding window to traverse across the B-mode image with the step of one pixel, while calculating the entropy by the pixel values in the window. The entropy is assigned to the center pixel of the sliding window. The entropy image is obtained after getting the entropy values of all pixels. FE and WhNSE are two novel entropies first applied to parametric imaging. The detection abilities of regions of interest (ROI) and the contrast-to-noise ratio (CNR) were evaluated through simulations and clinical explorations. Results: In simulations, FE imaging showed the highest improvement in detecting hyperechoic ROIs, with a CNR gain up to 457.31% (p < 0.01) in simulations. WhNSE imaging demonstrated the best performance in hyperechoic ROI detection, with a CNR of 1.607 ± 0.816 (p = 0.05), significantly higher than B-mode images. Conclusions: The proposed pixel-based parametric imaging method based on fuzzy entropy and weighted horizontally normalized Shannon entropy both effectively enhance the contrast and detectability of ultrasound images. The imaging enhancement method of the pixel-based fuzzy entropy imaging with proper parameters got better detection performance, due to the consideration of the relationship of neighboring pixels.

Combination of transcriptome and Mendelian inheritance reveals novel prognostic biomarker of CTLA-4-related lncRNAs and protective role of nitrogen metabolism pathway in lung adenocarcinoma development.

OBJECTIVE: Since in the cancer setting, tumor cells may use cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to evade the immune system. This study aimed to identify CTLA-4-related long non-coding RNAs (lncRNAs) and assess their roles in lung adenocarcinoma (LUAD) development. METHODS: Clinical and genomic data were obtained from The Cancer Genome Atlas (TCGA), MSigDB and Gene Weaver. CTLA-4-related lncRNA-based gene signatures (CTLA4LncSigs) were identified using Cox regression, establishing a risk score model and an independent prognostic model. Enrichment analysis (GO/KEGG) was performed. Mendelian randomization (MR) analysis investigated the nitrogen metabolism and lung cancer relationship, with Bayesian weighted MR (BWMR) addressing uncertainties. Correlations with tumor microenvironment and drug sensitivity were explored. RESULTS: Nineteen CTLA4LncSigs significantly influenced LUAD prognosis. The risk score demonstrated independence as a prognostic factor. Functional analysis revealed lncRNAs' impact on nitrogen metabolism. MR and BWMR confirmed the protective role of the nitrogen metabolism pathway in lung cancer. CONCLUSION: Our study identifies CTLA-4-related lncRNAs associated with LUAD prognosis and uncovers a previously undiscovered protective role of the nitrogen metabolism pathway in combating LUAD development, providing new insights into potential therapeutic targets and prognostic biomarkers for this aggressive cancer subtype.

Experiences of Chinese Rheumatoid Arthritis Patients Who Chose Western Medicine, Traditional Chinese Medicine, and a Combination of Treatments: A Study Based on Interviews and Thematic Analysis.

Background: This qualitative study, part of a prospective mixed-methods research, aimed to gain insights into the medical experiences and disease perceptions of Chinese patients living with rheumatoid arthritis (RA). Specifically, the study examined how RA patients' perceptions of their disease were influenced by the diagnosis and treatment they receive. Methods: RA patients undergoing treatment were invited to participate in this qualitative study. Face-to-face semi-structured interviews were conducted among 18 patients, and the collected data were analyzed using thematic analysis. Results: The 18 participants in this study had a mean (SD) age of 58, a median disease duration of 6.5 years, and a predominance of female subjects (17 out of 18). The qualitative analysis identified two themes with six sub-themes: 1. Patients' experiences of treatment: discovery of the disease, misdiagnosis and mistreatment, and patients' treatment choices; 2. Feelings about the disease: psychological impact, reflections on the disease, and expectations of treatment. Conclusion: This study provides valuable perspectives and data to enhance the understanding of the relationship between patients' illness perceptions and their healthcare choices.

Structural and genetic basis for the binding of a mouse monoclonal antibody to Flavobacterium psychrophilum lipopolysaccharide.

A mouse monoclonal antibody (mAb FL100A) previously prepared against Flavobacterium psychrophilum (Fp) CSF259-93 has now been examined for binding to lipopolysaccharides (LPS) of this strain and Fp 950106-1/1. The corresponding O-polysaccharides (O-PS) of these strains are formed by identical trisaccharide repeats composed of l-Rhamnose (l-Rha), 2-acetamido-2-deoxy-l-fucose (l-FucNAc) and 2-acetamido-4-R1-2,4-dideoxy-d-quinovose (d-Qui2NAc4NR1) where R1 represents a dihydroxyhexanamido moiety. The O-PS loci of these strains are also identical except for the gene (wzy1 or wzy2) that encodes the polysaccharide polymerase. Accordingly, adjacent O-PS repeats are joined through d-Qui2NAc4NR1 and l-Rha by wzy2-dependent α(1-2) linkages in Fp CSF259-93 versus wzy1-dependent ß(1-3) linkages in Fp 950106-1/1. mAb FL100A reacted strongly with Fp CSF259-93 O-PS and LPS but weakly or not at all with Fp 950106-1/1 LPS and O-PS. Importantly, it also labelled cell surface blebs on the former but not the latter strain. Additionally, mAb binding was approximately 5-times stronger to homologous Fp CSF259-93 LPS than to LPS from a strain with a different R-group gene. A conformational epitope for mAb FL100A binding was suggested from molecular dynamic simulations of each O-PS. Thus, Fp CSF259-93 O-PS formed a stable well-defined compact helix in which the R1 groups were displayed in a regular pattern on the helix exterior while unreactive Fp 950106-1/1 O-PS adopted a flexible extended linear conformation. Taken together, the findings establish the specificity of mAb FL100A for Wzy2-linked F. psychrophilum O-PS and LPS.

GHz-rate 57-fs acousto-optic mode-locking fiber laser based on cascaded all-fiber pulse compression.

We demonstrate a compact ultrafast fiber laser system that can deliver 1.87 GHz pulse train at 1550 nm with a pulse energy of 52 pJ and an ultrashort pulse duration of 57 fs. While an acousto-optic mode-locking fiber laser was used as the seed light source at GHz rate, a stage of Er-doped fiber amplifier boosted the laser power to ∼320 mW, giving a pulse energy of ∼170 pJ. Then, a pulse compression setup was constructed, providing a high compression ratio of ∼10 with a total efficiency of ∼32%. In the cascaded compression configuration, multiple fiber samples with alternately normal and anomalous dispersion were fused together, providing efficient nonlinear spectral broadening while suppressing excessive pulse broadening over propagation. This GHz-rate ultrafast fiber laser, with compact configuration, broad optical spectrum, and high time-resolving ability could be used as the seed light source for constructing high-rate, high-power ultrafast laser systems and may find a few applications in optical measurements and microwave photonics.

Preliminary research on LncRNA ATP2B2-IT2 in neovascularization of diabetic retinopathy.

OBJECTIVE: Diabetic retinopathy (DR) is a common complication of diabetes, and recent findings have shown that long noncoding RNAs (lncRNAs) may be involved in its pathogenesis. Through bioinformatics analysis, we found that lncRNA ATP2B2-IT2 may be involved in this process. This study primarily investigated the expression of the lncRNA ATP2B2-IT2 in human retinal microvascular endothelial cells (HRMECs) under high-glucose conditions and its effects on HRMEC proliferation, migration, and neovascularization. METHODS: We used RT‒PCR to assess the expression levels of lncRNA ATP2B2-IT2 and vascular endothelial growth factor (VEGF) in HRMECs under normal glucose (5.5 mmol/L) and high glucose (30 mmol/L) conditions. HRMECs were subsequently divided into four groups: the normal glucose (NG), high glucose (HG), high glucose with lncRNA ATP2B2-IT2 silencing (HG + si-lncRNA ATP2B2-IT2), and high glucose with silencing control (HG + si-NC) groups. The expression levels of the lncRNA ATP2B2-IT2 and VEGF in each group were determined using RT‒PCR. Thereafter, cell proliferation, migration, and neovascularization were assessed using CCK-8, Transwell, and tube formation assays, respectively. RESULTS: RT‒PCR revealed that the expression levels of the lncRNA ATP2B2-IT2 and VEGF were greater in the HG group than in the NG group (P < 0.05). After silencing of the lncRNA ATP2B2-IT2, the expression of VEGF decreased significantly (P < 0.05). Subsequent CCK-8, Transwell, and tube formation assays demonstrated that compared to those in the NG group, the HRMECs in the HG group exhibited significantly increased proliferation, migration, and neovascularization (P < 0.05). However, after silencing of the lncRNA ATP2B2-IT2, the proliferation, migration, and neovascularization of HRMECs were significantly decreased in the HG + si-lncRNA ATP2B2-IT2 group compared to those in the HG group (P < 0.05). CONCLUSION: LncRNA ATP2B2-IT2 may promote the proliferation, migration and neovascularization of HRMECs under high-glucose conditions.

Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer.

BACKGROUND: Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL. METHODS: In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR. RESULTS: BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes. CONCLUSION: Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.

Selenium-modified activated coke: a high-capacity and facile designed Hg0 adsorbent for coal-fired flue gas.

The substantial amount of mercury emissions from coal-fired flue gas causes severe environmental contamination. With the Minamata Convention now officially in force, it is critical to strengthen mercury pollution control. Existing activated carbon injection technologies suffer from poor desulfurization performance and risk secondary-release risks. Therefore, considering the potential industrial application of adsorbents, we selected cost-effective and readily available activated coke (AC) as the carrier in this study. Four metal selenides-copper, iron, manganese, and tin-were loaded onto the AC to overcome the application problems of existing technologies. After 120 min of adsorption, the CuSe/AC exhibited the highest efficiency in removing Hg0, surpassing 80% according to the experimental findings. In addition, the optimal adsorption temperature window was 30-120 °C, the maximum adsorption rate was 2.9 × 10-2 mg·g-1·h-1, and the effectiveness of CuSe/AC in capturing Hg0 only dropped by 5.2% in the sulfur-containing atmosphere. The physicochemical characterization results indicated that the AC surface had a uniform loading of CuSe with a nanosheet structure resembling polygon and that the Cu-to-Se atomic ratio was close to 1:1. Finally, two possible Hg0 reaction pathways on CuSe/AC were proposed. Moreover, it was elucidated that the highly selective binding of Hg0 with ligand-unsaturated Se- was the key factor in achieving high adsorption efficiency and sulfur resistance in the selenium-functionalized AC adsorbent. This finding offers substantial theoretical support for the industrial application of this adsorbent.

Biology of tongue coating in different disease stages of RA and its value in disease progression.

OBJECTIVE: To assess and compare the composition of tongue coating microbiota among patients at different stages of rheumatoid arthritis (RA). METHODS: A total of 47 patients diagnosed with RA, as per the American College of Rheumatology criteria, and 10 healthy individuals were enrolled in this study. The RA patients were stratified considering their Disease Activity Score 28 (DAS28), a composite measure based on the 28 tender and swollen joint count and erythrocyte sedimentation rate (ESR). The study population was further categorized into active phase group (LMH group) and inactive phase group (RE group) according to their DAS28 values. DNA extraction was extracted from tongue coating samples. Subsequently, the V3-V4 16S rDNA region was selectively amplified and sequenced through high-throughput 16S rDNA analysis. The resulting data were then utilized to ascertain the microbial contents. RESULTS: Significant variations were observed in the tongue coating microbiota of patients with RA during active and inactive phases, in comparison to healthy individuals (p < 0.05). At the genus level, the presence of Prevotellan, Veillonella, Rothia, and Neisseria in RA patients was notably more evident than in the healthy control (HC) group. These disparities find support in existing research on gut and oral microbiota. During the active phase of RA, the relative abundance of Veillonella, Rothia, and Neisseria in the tongue coating microbiota of patients was significantly higher than in those with inactive RA. These findings underscore the need for further and in-depth research on the potential impact of these microorganisms on the progression of RA disease. CONCLUSION: The results substantiate the hypothesis that tongue coating microbes actively contribute to the progression of RA.

Does Inter-Residue Hydrogen Bonding in ß-(1→4)-Linked Disaccharides Influence Linkage Conformation in Aqueous Solution?

Two disaccharides, methyl ß-d-galactopyranosyl-(1→4)-α-d-glucopyranoside (1) and methyl ß-d-galactopyranosyl-(1→4)-3-deoxy-α-d-ribo-hexopyranoside (3), were prepared with selective 13C-enrichment to allow measurement of six trans-O-glycosidic J-couplings (2JCOC, 3JCOCH, and 3JCOCC) in each compound. Density functional theory (DFT) was used to parameterize Karplus-like equations that relate these J-couplings to either ϕ or ψ. MA'AT analysis was applied to both linkages to determine mean values of ϕ and ψ in each disaccharide and their associated circular standard deviations (CSDs). Results show that deoxygenation at C3 of 1 has little effect on both the mean values and librational motions of the linkage torsion angles. This finding implies that, if inter-residue hydrogen bonding between O3H and O5' of 1 is present in aqueous solution and persistent, it plays little if any role in dictating preferred linkage conformation. Hydrogen bonding may lower the energy of the preferred linkage geometry but does not determine it to any appreciable extent. Aqueous 1-µs MD simulation supports this conclusion and also indicates greater conformational flexibility in deoxydisaccharide 3 in terms of sampling several, conformationally distinct, higher-energy conformers in solution. The populations of these latter conformers are low (3-14%) and could not be validated by MA'AT analysis. If the MD model is correct, however, C3 deoxygenation does enable conformational sampling over a wider range of ϕ/ψ values, but linkage conformation in the predominant conformer is essentially identical in both 1 and 3.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 674 (2024)10.1364/OL.509981.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation.

We demonstrate that through inserting a short length of highly birefringent small-core photonic crystal fiber (Hi-Bi SC-PCF) into a soliton fiber laser, the nonlinear polarization rotation effect in this laser can be manipulated, leading to continuous tuning of the output pulse parameters. In experiments, we observed that by adjusting the polarization state of light launched into the Hi-Bi SC-PCF and varying the cavity attenuation, the laser spectral width can be continuously tuned from ∼7.1 to ∼1.7 nm, corresponding to a pulse-width-tuning range from ∼350 fs to ∼1.56 ps. During the parameter tuning, the output pulses strictly follow the soliton area theory, giving an almost constant time-bandwidth-product of ∼0.31. This soliton fiber laser, being capable of continuous parameter tuning, could be applied as the seed source in ultrafast laser systems and may find some applications in nonlinear-optics and soliton-dynamics experiments.

Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol.

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.

5-HT induces regulatory B cells in fighting against inflammation-driven ulcerative colitis.

Serotonin (5-hydroxytryptamine or 5-HT) is a neuroendocrine peptide endowed with immunomodulatory functions. Regulatory B cells (Bregs) play an important role in maintaining intestinal immune homeostasis. We analyzed the differences of 5-HT and Bregs between peripheral blood of ulcerative colitis (UC) and healthy controls (HC). Besides, 5-HT-treated B cells were adoptively transferred into colitis mice to elucidate the role of 5-HT in regulating Bregs. The level of serum 5-HT and IL-10 in UC patients was lower and both were negatively correlated with disease activity. 5-HT7 receptor (5-HT7R) was higher expressed on Bregs in UC. 5-HT promoted IL-10 production in Bregs through the activation of STAT3. And adoptive transfer of 5-HT-treated B cells alleviated intestinal inflammation via inducing IL-10-producing B cells in mice. Our results suggest that 5-HT/5-HT7R signaling pathway facilitate functional Bregs in constraining inflammation in UC, which may be a new potential prospect in the treatment of UC.

Tanshinone IIA inhibits cell viability and promotes PUMA-mediated apoptosis of oral squamous cell carcinoma.

Apoptosis alteration is responsible for tumorigenesis and tumor resistance to therapies. The natural product Tanshinone IIA (Tan IIA) exhibits potent inhibitory effects against various tumors. However, the effect of Tan IIA on apoptosis and its underlying mechanism remains elusive in oral squamous cell carcinoma (OSCC). Here, we demonstrated that Tan IIA dose-dependently suppressed cell viability and colony formation in CAL27, SCC4, and SCC25 cells. Moreover, Tan IIA inhibited Akt activation from inducing Foxo3a dephosphorylation and PUMA-mediated apoptosis. PUMA or Foxo3a knockdown compromised the inhibitory effect of Tan IIA on OSCC cells. Tan IIA administration inhibited CAL27-deprived xenograft tumor growth and increased PUMA expression in vivo. Tan IIA synergistically intensified the efficacy of CDDP/5-FU-based chemotherapy on OSCC cells. Overall, our results revealed that Tan IIA exerted potent antitumor effects via promoting PUMA-mediated apoptosis in OSCC cells.

Sequence variety in the CC' loop of Siglec-8/9/3 determines the recognitions to sulfated oligosaccharides.

Siglecs are important lectins found in different types of immune cells and function as regulatory molecules by recognizing self-associated glycans and converting extracellular interactions into signals for inhibiting immune cell functions. Although many Siglecs have been found to show broad specificities and recognize different types of sulfated oligosaccharides, Siglec-8 and Siglec-9 displayed a high degree of specificity for sialyl N-acetyllactosamine (sLacNAc) with sulfations at O6-positions of the galactose (6'-sulfation) and N-acetylglucosamine (6-sulfation), respectively. Siglec-3 was recently discovered to bind sLacNAc both sulfations. In addition to a conserved arginine residue for binding to sialic acid residue, the sequence variety in the CC' loop may provide binding specificities to sulfated oligosaccharides in Siglecs. Thus, the present study employed molecular models to study the impact of different residues in the CC' loops of Siglec-8/9/3 to the recognitions of 6-sulfations in Gal and/or GlcNAc of sLacNAc. The negatively charged residues in the CC' loop of Siglec-9 formed unfavorable electrostatic repulsions with the 6-sulfate in Gal and resulted no recognitions, in contrast to the favorable interactions formed between the positively charged residues in the CC' loop of Siglec-8 and the 6-sulfate in Gal resulting strong specificity. A two-state binding model was proposed for Siglec-3 recognizing 6-sulfations in Gal and GlcNAc of sLacNAc, as the neutral residues in the CC' loop of Siglec-3 could not form strong favorable interactions to lock the 6-sulfate in Gal within a single binding pose or strong unfavorable interactions to repel the 6-sulfate in Gal. The oligosaccharide adopted two distinctive binding poses and oriented the sulfate groups to form interactions with residues in the CC' loop and G-strand. The present study provided a structural mechanism for the sequence variety in the CC' loop of Siglec-8/9/3 determining the recognitions to the sulfated oligosaccharides and offered insights into the binding specificities for Siglecs.

Dioscin inhibiting EGFR-mediated Survivin expression promotes apoptosis in oral squamous cell carcinoma cells.

Overexpression of survivin plays a crucial role in tumorigenesis and correlates with poor prognosis in human malignancies, including oral squamous cell carcinoma (OSCC). Thus, survivin has been proposed as an attractive target for new antitumor interventions. In the present study, we found that a natural compound, Dioscin, inhibited OSCC cells by reducing the survivin protein level and activating apoptotic signaling. Dioscin inhibits survivin expression by interrupting EGFR binding to the AT-rich sequences (ATRSs) at the survivin promoter, eventually promoting survivin-mediated cell apoptosis. The in vivo study showed that Dioscin suppressed the tumor development of SCC25 cells. Furthermore, the immunohistochemistry (IHC) results revealed that treated with Dioscin reduced the protein levels of EGFR and survivin in SCC25 xenograft tumors. Overall, our findings indicate that targeting the EGFR-survivin axis might be a promising OSCC treatment strategy.

Small extracellular vesicles-transported lncRNA TDRKH-AS1 derived from AOPPs-treated trophoblasts initiates endothelial cells pyroptosis through PDIA4/DDIT4 axis in preeclampsia.

BACKGROUND: Substantial studies have demonstrated that oxidative stress placenta and endothelial injury are considered to inextricably critical events in the pathogenesis of preeclampsia (PE). Systemic inflammatory response and endothelial dysfunction are induced by the circulating factors released from oxidative stress placentae. As a novel biomarker of oxidative stress, advanced oxidation protein products (AOPPs) levels are strongly correlated with PE characteristics. Nevertheless, the molecular mechanism underlying the effect of factors is still largely unknown. METHODS: With the exponential knowledge on the importance of placenta-derived extracellular vesicles (pEVs), we carried out lncRNA transcriptome profiling on small EVs (sEVs) secreted from AOPPs-treated trophoblast cells and identified upregulated lncRNA TDRKH-AS1 as a potentially causative factor for PE. We isolated and characterized sEVs from plasma and trophoblast cells by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. The expression and correlation of lncRNA TDRKH-AS1 were evaluated using qRT-PCR in plasmatic sEVs and placentae from patients. Pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs was performed to detect the TDRKH-AS1 function in vivo. To investigate the potential effect of sEVs-derived TDRKH-AS1 on endothelial function in vitro, transcriptome sequencing, scanning electron Microscopy (SEM), immunofluorescence, ELISA and western blotting were conducted in HUVECs. RNA pulldown, mass spectrometry, RNA immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP) and coimmunoprecipitation (Co-IP) were used to reveal the latent mechanism of TDRKH-AS1 on endothelial injury. RESULTS: The expression level of TDRKH-AS1 was significantly increased in plasmatic sEVs and placentae from patients, and elevated TDRKH-AS1 in plasmatic sEVs was positively correlated with clinical severity of the patients. Moreover, pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs exhibited a hallmark feature of PE with increased blood pressure and systemic inflammatory responses. Pyroptosis, an inflammatory form of programmed cell death, is involved in the development of PE. Indeed, our in vitro study indicated that sEVs-derived TDRKH-AS1 secreted from AOPPs-induced trophoblast elevated DDIT4 expression levels to trigger inflammatory response of pyroptosis in endothelial cells through interacting with PDIA4. CONCLUSIONS: Herein, results in the present study supported that TDRKH-AS1 in sEVs isolated from oxidative stress trophoblast may be implicated in the pathogenesis of PE via inducing pyroptosis and aggravating endothelial dysfunction.