Expanding the insight of ecological risk on the novel chiral pesticide mefentrifluconazole: Mechanism of enantioselective toxicity to earthworms (Eisenia fetida).

Continued application of new chiral fungicide mefentrifluconazole (MFZ) increases its risk to soil ecosystem. However, the toxicity of MFZ enantiomers to soil fauna and whether stereoselectivity exists remains poorly elucidated. Based on multilevel toxicity endpoints and transcriptomics, we investigated the negative effects of racemic, R-(-)-, and S-(+)-MFZ on Eisenia fetida. After exposure to S-(+) configuration at 4 mg/kg for 28 day, its reactive oxygen species levels were elevated by 15.4% compared to R-(-) configuration, inducing enantiospecific oxidative stress and transcriptional aberrations. The S-(+) isomer induced more severe cell membrane damage and apoptosis than the R-(-) isomer, and notably, the selectivity of apoptosis is probably dominated by the mitochondrial pathway. Mechanistically, differential mitochondrial stress lies in: S-(+) isomer specifically up-regulated mitochondrial cellular component compared to R-(-) isomer and identified more serious mitochondrial fission. Furthermore, S-(+) conformation down-regulated biological processes associated with ATP synthesis and metabolism, with specific inhibition of mitochondrial respiratory electron transport chain complex I and IV activity resulting in more severe electron flow disturbances. These ultimately mediated enantioselective ontogenetic process disorders, which were supported at phenotypic (weight loss), genetic, and protein (reverse modulate TCTP and Sox2 expression) levels. Our findings offer an important reference for elucidating the enantioselective toxicological mechanism of MFZ in soil fauna.

Mechanism of the adverse outcome of Chlorella vulgaris exposure to diethyl phthalate: Water environmental health reflected by primary producer toxicity.

As a ubiquitous contaminant in aquatic environments, diethyl phthalate (DEP) is a major threat to ecosystems because of its increasing utilization. However, the ecological responses to and toxicity mechanisms of DEP in aquatic organisms remain poorly understood. To address this environmental concern, we selected Chlorella vulgaris (C. vulgaris) as a model organism and investigated the toxicological effects of environmentally relevant DEP concentrations at the individual, physiological, biochemical, and molecular levels. Results showed that the incorporation of DEP significantly inhibited the growth of C. vulgaris, with inhibition rates ranging from 10.3 % to 83.47 %, and disrupted intracellular chloroplast structure at the individual level, while the decrease in photosynthetic pigments, with inhibition rates ranging from 8.95 % to 73.27 %, and the imbalance of redox homeostasis implied an adverse effect of DEP at the physio-biochemical level. Furthermore, DEP significantly reduced the metabolic activity of algal cells and negatively altered the cell membrane integrity and mitochondrial membrane potential. In addition, the apoptosis rate of algal cells presented a significant dose-effect relationship, which was mainly attributed to the fact that DEP pollutants regulated Ca2+ homeostasis and further increased the expression of Caspase-8, Caspase-9, and Caspase-3, which are associated with internal and external pathways. The gene transcriptional expression profile further revealed that DEP-mediated toxicity in C. vulgaris was mainly related to the destruction of the photosynthetic system, terpenoid backbone biosynthesis, and DNA replication. Overall, this study offers constructive understandings for a comprehensive assessment of the toxicity risks posed by DEP to C. vulgaris.

Photocatalytic degradation of butyl benzyl phthalate by S-scheme Bi/Bi2O2CO3/Bi2S3 under simulated sunlight irradiation.

As a kind of plasticizer, butyl benzyl phthalate (BBP) presents a serious hazard to the ecosystem. Therefore, there is a strong need for an effective technique to eliminate the risk of BBP. In this work, a new photocatalyst of Bi/Bi2O2CO3/Bi2S3 with an S-scheme heterojunction was synthesized using Bi(NO3)3 as the Bi source, Na2S as the S source, and DMF as the carbon source and reductant. Numerous techniques have been used to characterize Bi/Bi2O2CO3/Bi2S3, such as scanning electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The improved photoactivity of Bi/Bi2O2CO3/Bi2S3 was evaluated by photoelectrochemical response, electrochemical impedance spectroscopy, photoluminescence, UV-Vis diffuse reflectance spectroscopy, and electrochemical Mott Schottky spectroscopy. The enhanced photocatalytic activity of this composite for BBP degradation under simulated sunlight irradiation could be attributed to the surface plasmon resonance effect of Bi metal and the heterojunction structure of Bi2O2CO3 and Bi2S3. The degradation rate of Bi/Bi2O2CO3/Bi2S3 was 85%, which was 4.52 and 1.52 times that of Bi2O2CO3 and Bi2S3, respectively. The prepared photocatalyst possessed good stability and reproducibility in eliminating BBP. The improved photocatalytic activity of Bi/Bi2O2CO3/Bi2S3 was demonstrated with the formation of an S-scheme heterojunction, and the degradation mechanism was discussed with a liquid chromatograph mass spectrometer.

Stool-softening effect and action mechanism of free anthraquinones extracted from Rheum palmatum L. on water deficit-induced constipation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that rhubarb extract has a purgative effect when given to experimental animals in an appropriate dose. However, the active components and their mechanism of action are still not clearly defined. AIM OF THE STUDY: The current research aimed to evaluate the synergistic stool-softening effects and explore the action mechanism of rhubarb free anthraquinones (RhA) and their monomers on constipation in rats. MATERIALS AND METHODS: A rat model of water deficit-induced constipation was established to induce constipation, and these rats were treated with RhA and its monomers. ELISA, histopathology, immunohistochemistry, qPCR and Western blotting based on network pharmacology and molecular docking were conducted to explore the possible mechanism of action of RhA and its monomers. RESULTS: RhA, aloe-emodin, rhein, and chrysophanol showed stool-softening activity, and the combination of aloe-emodin and rhein had the strongest softening effect on faecal pellets. Aloe-emodin, rhein, and chrysophanol significantly increased the serum levels of vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP), upregulated the expression of VIP, cyclase-associated protein 1 (CAP1), protein kinase A (PKA), cystic fibrosis transmembrane conductance regulator (CFTR), aquaporin 3 (AQP3), aquaporin 4 (AQP4), and aquaporin 8 (AQP8), decreased the expression of epithelial sodium channel (ENaC) and Na+/H+ exchanger 3 (NHE3), and reduced the colonic tissue concentration of Na+-K+-ATPase in the constipated rats. Osmolality of colonic fluid in model rats treated by RhA, aloe-emodin, rhein, and chrysophanol was increased. CONCLUSION: Aloe-emodin, rhein, and chrysophanol were the stool-softening components of the RhA extract, and there were certain drug-interactions between the components. RhA upregulated VIP expression, activated the cyclic adenosine monophosphate protein kinase A (cAMP/PKA) pathway, and further stimulated CFTR expression while inhibiting NHE3 and ENaC expression, resulting in a hypertonic state in the colonic lumen. Water transport could then be driven by an osmotic gradient, which in turn led to the upregulation of AQP3, AQP4, and AQP8 expression. In addition, RhA likely improved gastrointestinal motility by increasing serum VIP, SP, and MTL concentrations, thus promoting faecal excretion.

Occurrence and health risk assessment of phthalates in a typical estuarine soil: A case study of the various functional areas of the Yellow River Delta.

In recent years, the extensive distribution of phthalates (PAEs) in soils has attracted increasing attention. In this study, the concentrations of six types of PAEs were measured in five dissimilar regions of the Yellow River Delta (YRD), and regional differences, pollution characteristics and health risks of PAEs pollution were investigated. The detection rate of PAEs was 100 %, and the concentration range of Σ6PAEs was 0.709-9.565 mg/kg, with an average of 3.258 ± 2.031 mg/kg. There were different spatial distribution differences of PAEs in soils of the YRD, with residential living, chemical industrial, and crop growing areas being the main areas of PAEs distribution. It was worth noting that di (2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) are prominent contributors to PAEs in soils of the YRD. Correlation analyses showed that soils physicochemical properties such as SOM, TN and CEC were closely correlated to the transport and transformation of PAEs. Use by petrochemical industries, accumulation of plasticizers, additives (derived from cosmetics, food, pharmaceutical), fertilizers, pesticides, plastics, and atmospheric deposition are the principal sources of PAEs in the YRD. A health risk assessment showed that the health risk caused by non-dietary intake of PAEs was low and considered acceptable. PAEs pollution in the YRD soil is particularly noteworthy, especially for the prevention and control of DEHP and DBP pollution. This study provides basic data for an effective control of soil PAEs pollution in the YRD, which is conducive to the sustainable development of the region.

Multi-level biological effects of diverse alkyl chains phthalate esters on cotton seedlings (Gossypium hirsutum L.): Insights into individual, physiological-biochemical and molecular perspectives.

Phthalate esters (PAEs) are organic contaminants that pose environmental threat and safety risks to soil health and crop production. However, the ecological toxicity of different PAEs to cotton and the underlying mechanisms are not clear. This study investigated the ecotoxic effects and potential mechanisms of different alkyl-chain PAEs, including dioctyl phthalate (DOP), dibutyl phthalate (DBP), and diethyl phthalate (DEP) on cotton seedlings at multiple levels. The results showed that PAEs significantly hindered the growth and development of cotton. The chlorophyll content decreased by 1.87-31.66 %, accompanied by non-stomatal photosynthetic inhibition. The antioxidant system was activated by the three PAEs in cotton seedlings, while the osmotic potential was boosted intracellularly. Additionally, PAEs significantly interfered with functional gene expression and exhibited genotoxicity. Risk assessment results indicated that the ecotoxicity was DOP >DBP >DEP, with a "dose-response" relationship. The affinity between the three PAEs and catalase increased as the alkyl chain length increased, further supporting the toxicity sequence. Surprisingly, the bioconcentration factors of short-chain DEP were 8.07 ± 5.89 times and 1837.49 ± 826.83 times higher than those of long-chain DBP and DOP, respectively. These results support the ecological risk assessment of PAEs in cotton and provide new insights into determining the toxicity levels of different PAEs.

Treatment patterns and clinical outcomes of mantle cell lymphoma: A retrospective cohort study by CHOICE.

Regimens based on Bruton's tyrosine kinase inhibitors (BTKi) have been increasingly used to treat mantle cell lymphoma (MCL). A real-world multicenter study was conducted to characterize treatment patterns and outcomes in patients with newly diagnosed MCL by Chinese Hematologist and Oncologist Innovation Cooperation of the Excellent (CHOICE). The final analysis included 1261 patients. Immunochemotherapy was the most common first-line treatment, including R-CHOP in 34%, cytarabine-containing regimens in 21% and BR in 3% of the patients. Eleven percent (n = 145) of the patients received BTKi-based frontline therapy. Seventeen percent of the patients received maintenance rituximab. Autologous hematopoietic stem cell transplantation (AHCT) was conducted in 12% of the younger (<65 years) patients. In younger patients, propensity score matching analysis did not show significant difference in 2-year progression-free survival and 5-year overall survival rate in patients receiving standard high-dose immunochemotherapy followed by AHCT than induction therapy with BTKi-based regimens without subsequent AHCT (72% vs 70%, P = .476 and 91% vs 84%, P = .255). In older patients, BTKi combined with bendamustine plus rituximab (BR) was associated with the lowest POD24 rate (17%) compared with BR and other BTKi-containing regimens. In patients with resolved hepatitis B at the baseline, HBV reactivation rate was 2.3% vs 5.3% in those receiving anti-HBV prophylaxis vs not; BTKi treatment was not associated with higher risk of HBV reactivation. In conclusion, non-HD-AraC chemotherapy combined with BTKi may be a viable therapeutic strategy for younger patients. Anti-HBV prophylaxis should be implemented in patients with resolved hepatitis B.

Research trends of acupuncture therapy on dysmenorrhea from 2002 to 2022: A bibliometric analysis.

This research wasdesigned to provide a visual analysis of the current status, hotspots, and trends of global acupuncture for dysmenorrhea over the past 2 decades. The literature about acupuncture for dysmenorrhea from the Web of Science Core Collection database. Cite Space (5.6.R3) was used to analyze the volume of publications, journals, authors, cited journals, cited authors, countries, cited references, institutions, and keywords by using standard bibliometric measures. The most productive countries and institutions in this area were China (79) and BeijingUniversity of Chinese Medicine (24). The Evidence-Based Complementary and Alternative Medicine was the most published journal (29) and also had the highest number of citations (80). The article by Woo HL (2018) (number of citations: 13) and the article by (centrality: 0.38) were the most representative references. JiangZhu (17) was the most productive author and Dawood MY (47) was the top cited author. The number one keyword in terms of frequency and centrality was 'primary dysmenorrhea", and the leading hotspot from 2002 to 2022 was "Functional connectivity". The three forefront topics were "prevalence", "impact"and "point'. This research is thefirst bibliometric analysis of the current situation and new trends about acupuncture for dysmenorrhea in the past 20 years using CiteSpace. It offered some information on acupuncture for dysmenorrhea and valuable information for researchers to identify prospective collaborators, partner institutions, popular topics, and research frontiers.

Evaluation of soil ecological health after exposure to environmentally relevant doses of Di (2-ethylhexyl) phthalate: Insights from toxicological studies of earthworms at different ecological niches.

As one of the most critical soil faunas in agroecosystems, earthworms are significant in preserving soil ecological health. Di (2-ethylhexyl) phthalate (DEHP) is a major plasticizer and widely used in plastic products like agricultural films. However, it has become ubiquitous contaminant in agricultural soil and poses a potential threat to soil health. Although the awareness of the impacts of DEHP on soil ecology is increasing, its adverse effects on soil invertebrates, especially earthworms, are still not well developed. In this study, the ecotoxicological effects and underlying mechanisms of environmentally relevant doses DEHP on earthworms of different ecological niches were investigated at the individual, cytological, and biochemical levels, respectively. Results showed that the acute toxicity of DEHP to M. guillelmi was higher than E. foetida. DEHP induced reactive oxygen species (ROS) levels and further caused oxidative damage (including cellular DNA and lipid peroxidation damage) in both species, speculating that they may exhibit similar oxidative stress mechanisms. Furthermore, two earthworms presented the alleviated toxicity when re-cultured in uncontaminated circumstances, yet, the accumulated ROS in bodies could not be completely scavenged. Risk assessment indicated that the detrimental impacts of DEHP were more significant in the M. guillelmi than in E. foetida in whole experiments prides, and the biomarkers additionally showed a species-specific trend. Besides, molecular docking revealed that DEHP could bind to the active center of superoxide dismutase/catalase (SOD/CAT) by hydrogen bonding or hydrophobic interactions. Overall, this study will provide a novel insight for accurate contaminant risk assessment, and also highlight that the comprehensive biological effects of different species should be emphasized in soil ecological health diagnostics and environmental toxicology assays, as otherwise it may lead to underestimation or misestimation of the soil health risk of contaminants.

Occurrence, source, ecological risk, and mitigation of phthalates (PAEs) in agricultural soils and the environment: A review.

The widespread distribution of phthalates (PAEs) in agricultural soils is increasing drastically; however, the environmental occurrence and potential risk of PAEs in agricultural systems remain largely unreviewed. In this study, the occurrence, sources, ecotoxicity, exposure risks, and control measures of PAEs contaminants in agricultural soils are summarized, and it is concluded that PAEs have been widely detected and persist in the soil at concentrations ranging from a few µg/kg to tens of mg/kg, with spatial and vertical variations in China. Agrochemicals and atmospheric deposition have largely contributed to the elevated contamination status of PAEs in soils. In addition, PAEs cause multi-level hazards to soil organisms (survival, oxidative damage, genetic and molecular levels, etc.) and further disrupt the normal ecological functions of soil. The health hazards of PAEs to humans are mainly generated through dietary and non-dietary pathways, and children may be at a higher risk of exposure than adults. Improving the soil microenvironment and promoting biochemical reactions and metabolic processes of PAEs are the main mechanisms for mitigating contamination. Based on these reviews, this study provides a valuable framework for determining future study objectives to reveal environmental risks and reduce the resistance control of PAEs in agricultural soils.

[GAO Hong's clinical experience in treatment of tic disorder with acupuncture technique of cultivating the primary and regulating the mind].

The paper introduces the clinical experience of GAO Hong in treatment of tic disorder. GAO Hong believes that tic disorder results from the primary qi deficiency and mind disturbance. Acupuncture for cultivating the primary and regulating the mind is proposed specially for tic disorder. This acupuncture technique focuses on harmonizing and regulating governor vessel and conception vessel. In clinical practice, the conception vessel acupoints on the abdomen and the governor vessel acupoints on the head are selected particularly, e.g. Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6) and Guanyuan (CV 4) on the abdomen; Baihui (GV 20), Shenting (GV 24), Benshen (GB 13) and Yintang (GV 24+) on the head. The needling sequence and the insertion depth are emphasized, which affect the curative effect and GV 20 is generally punctured first. Besides, considering to the type of disorder and the affected site, tic disorder is treated in view of both syndrome/pattern differentiation and symptom differentiation.

Vascularized nanocomposite hydrogel mechanically reinforced by polyelectrolyte-modified nanoparticles.

Vascularization plays an important role in the initial stage of triggering bone defect repair. The combination of bioactive small molecule drugs and biomaterials has been a powerful strategy for vascularization in bone tissue engineering. In this study, an in situ crosslinked aldehyde hyaluronic acid (AHA)/N,O-carboxymethyl chitosan (NOCC) nanocomposite hydrogel doped with sphingosine 1-phosphate (S1P)-loaded polyelectrolyte-modified mesoporous silica nanoparticles (MSNs) was developed. The alginate/chitosan polyelectrolyte-modified MSNs (MSNs-ALG/CHI) were prepared via the electrostatic interaction. The incorporation of MSNs-ALG/CHI not only achieved a sustained release profile of the angiogenic drug, but also improved the mechanical property of the AHA/NOCC hydrogel due to the Schiff base reaction between the amino group in chitosan and the aldehyde group in AHA. In addition, in vitro cell experiments demonstrated that the nanocomposite hydrogel provided favorable support for cell adhesion and proliferation, and the S1P-loaded nanocomposite hydrogel was able to recruit endothelial cells. More importantly, the chicken chorioallantoic membrane (CAM) assay confirmed that the S1P-loaded nanocomposite hydrogel could significantly enhance capillary formation. More cell infiltration and better angiogenesis in the S1P loaded nanocomposite hydrogel were observed compared to the group without S1P loading after being implanted subcutaneously for 2 weeks. Furthermore, the subcutaneous implantation experiment further demonstrated that the incorporation of the S1P-loaded nanocomposite hydrogel could improve the tissue infiltration and new vessel formation within the macroporous poly(L-lactic acid)/polycaprolactone scaffold. Our results suggest that the nanocomposite hydrogel will be an excellent drug delivery system and the S1P-loaded nanocomposite hydrogel has great potential for vascularized bone regeneration application.

A novel clinical immune-related prognostic model predicts the overall survival of mantle cell lymphoma.

The mantle cell lymphoma (MCL) International Prognostic Index (MIPI) and combined MIPI (MIPI-c) are commonly used for risk classification of MCL patients. However, these indexes lack immune-related parameters. The purpose of this study was to develop a novel prognostic model that integrated clinical and immune parameters. A total of 189 patients with newly diagnosed MCL from January 2010 to June 2020 were enrolled in our study. A nomogram and immune-related prognostic index (IRPI) were established to predict the overall survival (OS) of patients according to univariate and multivariate analyses. Discrimination and calibration were used to compare the prognostic performance of the IRPI, MIPI, and MIPI-c. External validation was performed based on validation dataset (n = 150) from two other centers. The results for the training dataset indicated that B symptoms, platelet count, B2M level, CD4+ T-cell count<26.7% and CD8+ T-cell count>44.2% were predictors for OS. All the prognostic factors were integrated into the nomogram. For the overlap of confidence intervals of each variable, we assigned one point for each factor. The IRPI categorized patients into three risk categories: a score of zero indicated low risk, a score of one or two indicated intermediate risk, and a score of ≥3 indicated high risk. The IRPI showed better discrimination and calibration power than the MIPI and MIPI-c in the training dataset and validation dataset. The novel IRPI is a refined risk stratification index and reflects the strong complementary prognostic effects between clinical and immune parameters in MCL.

Identification and action mechanism of lipid regulating components from Rhei Radix et rhizoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhei Radix et Rhizoma is widely used in Traditional Chinese Medicine to attack stagnation, clear damp heat, relieve fire, cool blood, remove blood stasis and detoxify recorded in Chinese Pharmacopoeia. Modern pharmacological research has showed the extract of Rhei Radix et Rhizoma has the effect of lowering blood lipids, but the main active components and their mechanisms are still not clear. AIM OF THE STUDY: To reveal the lipid regulating components from Rhei Radix et Rhizoma and preliminarily explore their related action mechanisms. MATERIALS AND METHODS: A rat model of dyslipidemia was established by administration of a high-fat emulsion via gavage, and the intervention effect of different polar fractions of Rhei Radix et Rhizoma on rat blood lipids as well as their related action mechanisms were preliminarily investigated. The effective components were inferred based on the above tests and identified by high performance liquid chromatography in comparison with reference substances, their UV absorption and high resolution mass spectra characteristics. RESULTS: The extract with dichloromethane fraction (DF) containing rhubarb free anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) significantly regulated the disordered blood lipids, lowered TC and LDLC, reversed TG and increased HDLC level in dyslipidemic rats and also showed lipid-lowering effect on lipid abnormalities in HepG2 cells. DF could alter the signaling pathways such as PPARα and AMPK implicated in lipid metabolism, and it down-regulated the mRNA expression of liver APOA2, SCD-1, HMGCR, SREBP-2 and PCSK9, but up-regulated the expressions of liver APOE, LPL and intestinal ABCG8. Besides, it could change the composition of Firmicutes, Bacteroidetes and Proteobacteria in dyslipidemic rat feces samples. CONCLUSIONS: Rhubarb free anthraquinones have a significant regulating effect on the levels of serum TC, LDLC and HDLC, and probably possess a bidirectional regulatory effect on TG level in dyslipidemic rats. These effects may be achieved by regulating the expressions of the liver PPARα and SREBP target genes, PCSK9 and the intestinal ABCG8 genes, which are involved in blood cholesterol transport, liver lipid metabolism and intestinal cholesterol excretion. Rhubarb free anthraquinones may also affect energy metabolism by changing the composition of gut microflora related to lipid metabolism in dyslipidemic rats.

MEG3 LncRNA from Exosomes Released from Cancer-Associated Fibroblasts Enhances Cisplatin Chemoresistance in SCLC via a MiR-15a-5p/CCNE1 Axis.

PURPOSE: Long non-coding RNAs (lncRNAs) may act as oncogenes in small-cell lung cancer (SCLC). Exosomes containing lncRNAs released from cancer-associated fibroblasts (CAF) accelerate tumorigenesis and confer chemoresistance. This study aimed to explore the action mechanism of the CAF-derived lncRNA maternally expressed gene 3 (MEG3) on cisplatin (DDP) chemoresistance and cell processes in SCLC. MATERIALS AND METHODS: Quantitative real-time PCR was conducted to determine the expression levels of MEG3, miR-15a-5p, and CCNE1. Cell viability and metastasis were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide and invasion assays, respectively. A xenograft tumor model was developed to confirm the effect of MEG3 overexpression on SCLC progression in vivo. Relationships between miR-15a-5p and MEG3/CCNE1 were predicted using StarBase software and validated by dual luciferase reporter assay. Western blotting was used to determine protein levels. A co-culture model was established to explore the effects of exosomes on MEG3 expression in SCLC cell lines. RESULTS: MEG3 was overexpressed in SCLC tissues and cells. MEG3 silencing significantly repressed cell viability and metastasis in SCLC. High expression of MEG3 was observed in CAF-derived conditioned medium (CM) and exosomes, and promoted chemoresistance and cancer progression. Additionally, MEG3 was found to serve as a sponge of miR-15a-5p to mediate CCNE1 expression. Overexpression of miR-15a-5p and knockout of CCNE1 reversed the effects of MEG3 overexpression on cell viability and metastasis. CONCLUSION: MEG3 lncRNA released from CAF-derived exosomes promotes DDP chemoresistance via regulation of a miR-15a-5p/CCNE1 axis. These findings may provide insight into SCLC therapy.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Interface-Engineered Paclitaxel-Based Hollow Mesoporous Organosilica Nanoplatforms for Photothermal-Enhanced Chemotherapy of Tumor.

Having benefited from the combination of different therapeutic modalities, functionalized nanoplatforms with synergistic strategies have aroused great interest in anticancer treatment. Herein, an engineered, a biodegradable hollow mesoporous organosilica nanoparticle (HMON)-based nanoplatform was fabricated for photothermal-enhanced chemotherapy of tumor. For the first time, we demonstrated that HMONs could serve as nanocarriers for co-delivering of both the paclitaxel and photothermal agent new indocyanine green (IR820), denoted as Paclitaxel/IR820@ HMONs-PEG. The as-prepared nanosystem exhibited a high paclitaxel-loading capacity of 28.4%, much higher than most paclitaxel-loaded nanoformulations. Furthermore, incorporating thioether bonds (S-S) into the HMONs' framework endowed them with GSH-responsive biodegradation behavior, leading to the controllable release of drugs under a tumor reducing microenvironment, and hindered the premature release of paclitaxel. Upon being irradiated with an NIR laser, the obtained co-delivery nanosystem exhibited great photothermal properties generated from IR820. The fabricated nanocomposites could significantly suppress tumor growth under NIR laser irradiation, as validated by in vitro and in vivo assessments. Combined with outstanding biocompatibility, the constructed nanosystem holds great potential in combinational antitumor therapy.

JNK Pathway-Associated Phosphatase as a Serum Marker for Disease Activity and Treatment Outcome of Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by arthritis of unknown etiology. JNK pathway-associated phosphatase (JKAP) is reported to be a negative regulator of T-cell activation, but its clinical role in JIA is unknown. This study aimed to investigate the correlation of JKAP with disease activity and treatment response to a tumor necrosis factor (TNF) inhibitor, etanercept (ETN), in JIA patients. Totally, 104 JIA patients (6.9 ± 2.7 years old) and 100 age- and sex-matched healthy controls (HCs) (7.2 ± 2.4 years old) were enrolled, and their serum samples were collected for measuring JKAP by enzyme-linked immunoassay. In JIA patients, after 24-week ETN treatment, clinical response was assessed based on the American College of Rheumatology pediatric criteria (ACRpedi) 50 criteria. Results showed that JKAP levels were significantly lower in JIA patients compared with HCs, and of good value in differentiating JIA patients from HCs. Among JIA patients, higher JKAP levels were associated with lower disease activity indexes, including C-reactive protein, number of joints with active arthritis, physician's global assessment of disease activity, and the present history of disease-modifying antirheumatic drugs; higher baseline JKAP levels were correlated with worse ACRpedi 50 response to ETN at week 24, and was also an independent predictive factor for worse ACRpedi 50 response to ETN. Thus, it may be inappropriate to use ETN for JIA patients with higher JKAP levels. In conclusion, serum JKAP is a potential biomarker for JIA activity and treatment response to a TNF inhibitor.

Linoleic acid inhibits Lactobacillus activity by destroying cell membrane and affecting normal metabolism.

BACKGROUND: The reason why dietary polyunsaturated fatty acids (PUFAs) affect the activity of Lactobacillus remains unclear. In this study, linoleic acid was used to study the mechanism underlying its inhibition function against Lactobacillus activity. RESULTS: The growth curve of Lactobacillus rhamnosus LGG and the metabolite content in bacterial liquid were determined at varying linoleic acid concentration. The degree of cell membrane damage of L. rhamnosus LGG was determined by flow cytometry and fluorescence microscopy, and the cell structure was observed by scanning electron microscopy and transmission electron microscopy. The effect of linoleic acid on Lactobacillus activity was assessed in a simulated gut environment. Results showed that L. rhamnosus LGG grew slowly, cell metabolites leaked into the liquid, cell membrane was damaged, and the cell structure changed at a linoleic acid concentration of 50 µg mL-1 . CONCLUSION: The mechanism of action of linoleic acid on Lactobacillus showed that that linoleic acid destroyed the cell membrane of bacteria, thereby affecting the normal metabolism of the bacteria and ultimately leading to their death. © 2019 Society of Chemical Industry.

Clinical significance of enhancer of zeste homolog 2 and histone deacetylases 1 and 2 expression in peripheral T-cell lymphoma.

Epigenetics serve a key role in peripheral T cell lymphoma (PTCL). The purpose of the present study was to investigate the clinical significance of enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 and 2 (HDAC1/2) expression in PTCL. A total of 82 patients were enrolled in the present study, including 43 with PTCL not otherwise specified (PTCL-NOS), 10 with angioimmunoblastic T-cell lymphoma (AITL), 14 with natural killer/T-cell lymphoma (NK/TCL) and 15 with anaplastic large cell lymphoma (ALCL). EZH2 and HDAC1/2 expression was detected by immunohistochemistry and any correlations between them were evaluated. Additionally, any correlations between EZH2 or HDAC1/2 expression and a number of clinicopathological characteristics were analyzed, and survival curves were created. Results revealed that 55.8% of patients with PTCL-NOS, 57.1% of patients with NK/TCL, 86.7% of patients ALCL and 50% of patients with AITL highly expressed HDAC1. Furthermore, 58.1% of patients with PTCL-NOS, 57.1% of patients with NK/TCL, 53.3% of patients with ALCL and 60% of patients with AITL highly expressed HDAC2. Additionally, 67.5% of patients with PTCL-NOS, 50% of patients with NK/TCL, 73.3% of patients with ALCL and 60% of patients with AITL highly expressed EZH2. EZH2 expression was significantly correlated with the presence of B symptoms, elevated LDH and elevated ß2 microglobulin (B2M; P<0.05), and HDAC2 expression was significantly correlated with sex, advanced clinical stages, high international prognostic index scores and elevated B2M levels (P<0.05) in all the patients with PTCL. However, different subtypes of PTCL are correlated with different clinical characteristics. Patients with PTCL highly expressing EZH2 or HDAC2 exhibit a poorer overall survival rate. In conclusion, EZH2 and HDAC1/2 were frequently upregulated in patients with PTCL, and the patients with a higher EZH2 and HDAC2 expression usually exhibited a poorer survival rate. Therefore, EZH2 and HDAC2 may be prognostic markers in patients with PTCL, particularly in those with PTCL-NOS.