Maintenance of persistent transmission of a plant arbovirus in its insect vector mediated by the Toll-Dorsal immune pathway.

Throughout evolution, arboviruses have developed various strategies to counteract the host's innate immune defenses to maintain persistent transmission. Recent studies have shown that, in addition to bacteria and fungi, the innate Toll-Dorsal immune system also plays an essential role in preventing viral infections in invertebrates. However, whether the classical Toll immune pathway is involved in maintaining the homeostatic process to ensure the persistent and propagative transmission of arboviruses in insect vectors remain unclear. In this study, we revealed that the transcription factor Dorsal is actively involved in the antiviral defense of an insect vector (Laodelphax striatellus) by regulating the target gene, zinc finger protein 708 (LsZN708), which mediates downstream immune-related effectors against infection with the plant virus (Rice stripe virus, RSV). In contrast, an antidefense strategy involving the use of the nonstructural-protein (NS4) to antagonize host antiviral defense through competitive binding to Dorsal from the MSK2 kinase was employed by RSV; this competitive binding inhibited Dorsal phosphorylation and reduced the antiviral response of the host insect. Our study revealed the molecular mechanism through which Toll-Dorsal-ZN708 mediates the maintenance of an arbovirus homeostasis in insect vectors. Specifically, ZN708 is a newly documented zinc finger protein targeted by Dorsal that mediates the downstream antiviral response. This study will contribute to our understanding of the successful transmission and spread of arboviruses in plant or invertebrate hosts.

Hierarchical build-up of vertically oriented lignin-based aerogel for photothermally assisted uranium uptake and recovery from acidic wastewater.

Developing the lignin-based functional materials for uranium uptake is extremely attractive, but challenging due to the complex structure, poor solubility and reactivity of lignin. Herein, a novel phosphorylated lignin (LP)/sodium alginate/ carboxylated carbon nanotube (CCNT) composite aerogel (LP@AC) with vertically oriented lamellar configuration was created for efficient uranium uptake from acidic wastewater. The successful phosphorylation of lignin by a facile solvent-free mechanochemical method achieved more than six-times enhancement in U(VI) uptake capacity of lignin. While, the incorporation of CCNT not only increased the specific surface area of LP@AC, but also improved its mechanical strength as a reinforcing phase. More importantly, the synergies between LP and CCNT components endowed LP@AC with an excellent photothermal performance, resulting in a local heat environment on LP@AC and further boosting the U(VI) uptake. Consequently, the light irradiated LP@AC exhibited an ultrahigh U(VI) uptake capacity (1308.87 mg g-1), 61.26% higher than that under dark condition, excellent adsorptive selectivity and reusability. After exposure to 10 L of simulated wastewater, above 98.21% of U(VI) ions could be rapidly captured by LP@AC under light irradiation, revealing the tremendous feasibility in industrial application. The electrostatic attraction and coordination interaction were considered as the main mechanism for U(VI) uptake.

Efficient extraction of uranium from seawater by reticular polyamidoxime-functionalized oriented holocellulose bundles.

A novel multi-layered reticular polyamidoxime (PAO)-functionalized holocellulose bundles (ML-r-PAO@HB) with abundant oriented micro-channels and high mechanical strength was created via a facile solvent-exchange strategy and used for the first time to capture uranium from seawater. Due to the hydrophobic interaction of PAO chains induced by the solvent-exchange, multi-layered reticular PAO was successfully self-assembled onto the oriented micro-channels of the HB, which greatly improved the accessibility to the adsorption sites by increasing the exposed surface of PAO. The ML-r-PAO@HB exhibited high uptake capacity (851.42 mg g-1 PAO) and excellent adsorptive selectivity for U(VI) ions. After exposure to 500-L natural seawater for 28 days, an ultra-high uranium extraction capacity (9.74 mg g-1 PAO) was achieved by ML-r-PAO@HB. The N and O atoms in the -C(NH2)N-OH group were the main coordination sites for U(VI) uptake. These wonderful performances render the ML-r-PAO@HB highly desirable for the large-scale uranium extraction from seawater.

Socioeconomic Status Impacts the Prognosis of Chronic Rhinosinusitis Treated by Endoscopic Sinus Surgery: An Observational Cohort Study in Northeast China / 生物医学与环境科学（英文）

OBJECTIVE@#To explore the association between socioeconomic status (SES) and postoperative outcomes in patients with chronic sinusitis (CRS) after functional endoscopic sinus surgery (ESS).@*METHODS@#We conducted an observational cohort study of 1,047 patients with CRS undergoing ESS. Discharged patients were followed up to 72 weeks for all-cause recurrence events. Baseline SES was established based on occupation, education level, and family income of the patients 1 year before the operation. Kaplan-Meier method was used to calculate the recovery rate after ESS, and Cox proportional hazards regression analysis was used to evaluate the relationship between SES and prognosis.@*RESULTS@#Patients of middle SES had lower unadjusted all-cause recurrence than those of low or high SES; 24-week overall recovery rate was 90.4% [95 % confidence interval ( CI): 89.6%-91.2%] in patients of middle SES, 13.5% (95 % CI: 12.8%-14.2%) in patients of low SES, and 31.7% (95 % CI: 30.7%-32.7%) in patients of high SES (both log-rank P < 0.001). After adjustment for covariates, hazard ratios ( HRs) were 7.69 (95 % CI: 6.17-9.71, P trend < 0.001) for all-cause recurrence for low SES versus middle SES, and 6.19 (95 % CI: 4.78-7.93, P trend < 0.001) for middle SES versus high SES.@*CONCLUSION@#Low SES and high SES were more associated with the worse prognosis of CRS patients after ESS than middle SES.

Artificial intelligence-based CT metrics used in predicting clinical outcome of COVID-19 in young and middle-aged adults.

BACKGROUND: Currently, most researchers mainly analyzed coronavirus disease 2019 (COVID-19) pneumonia visually or qualitatively, probably somewhat time-consuming and not precise enough. PURPOSE: This study aimed to excavate more information, such as differences in distribution, density, and severity of pneumonia lesions between males and females in a specific age group using artificial intelligence (AI)-based computed tomography (CT) metrics. Besides, these metrics were incorporated into a clinical regression model to predict the short-term outcome. MATERIALS AND METHODS: The clinical, laboratory information and a series of HRCT images from 49 patients, aged from 20 to 50 years and confirmed with COVID-19, were collected. The volumes and percentages of infection (POIs) among bilateral lungs and each bronchopulmonary segment were extracted using uAI-Discover-NCP software (version R001). The POI in three HU ranges (i.e., <-300, -300-49, and ≥50 HU representing ground-glass opacity [GGO], mixed opacity, and consolidation) were also extracted. Hospital stay was predicted with several POI after adjusting days from illness onset to admission, leucocytes, lymphocytes, C-reactive protein, age, and gender using a multiple linear regression model. A total of 91 patients aged 20-50 from public database were selected. RESULTS: Right lower lobes had the highest POI, followed by left lower lobes, right upper lobes, middle lobes, and left upper lobes. The distributions in lung lobes and segments were different between the sexes. Men had a higher total POI and GGO of the lungs, but less consolidation than women in initial CT (all p < 0.05). The total POI, percentage of consolidation on initial CT, and changed POI were positively correlated with hospital stay in the model. A total of 91 patients aged 20-50 years in the public database were selected, and AI segmentation was performed. The POI of the lower lobes was obviously higher than that in the upper lobes; the POI of each segment of the right upper lobe in the males was higher than that in the females, which was consistent with the result of the 49 patients previously. CONCLUSION: Both men and women had characteristic distributions in lung lobes and bronchopulmonary segments. AI-based CT quantitative metrics can provide more precise information regarding lesion distribution and severity to predict clinical outcome.

High-efficiency capture and removal of phosphate from wastewater by 3D hierarchical functional biomass-derived carbon aerogel.

The development of functional biomass-based carbon aerogels (CAs) with excellent mechanical flexibility and ultra-high phosphate capture capacity is crucial for capture and recovery of phosphate from waste water. Herein, a functional biomass-derived CA (MgO@SL/CMC CA) with an ordered wave-shaped layered structure and excellent compressibility was fabricated with the aim of creating a material with efficient phosphate capture performance. The incorporation of sulfonomethylated lignin (SL) significantly improves the mechanical flexibility of MgO@SL/CMC CA. Numerous MgO nano-particles (NPs), which act as principal adsorption sites, were uniformly anchored on the MgO@SL/CMC CA. The prepared MgO@SL/CMC CA with high Mg content (20.34 wt%) exhibited an ultra-high phosphate capture capacity (218.51 mg P g-1 for adsorbent or 644.58 mg P g-1 for MgO), excellent adsorptive selectivity for phosphate and a wide pH range of application (2-8). Notably, more than 81.95% of the phosphate capture capacity was retained after six cyclic adsorption-desorption tests. A considerable effective treatment volume (468 BV) of actual wastewater (1.7 mg P L-1) could be achieved by the MgO@SL/CMC CA in the fixed-bed adsorption column. Research into the adsorption mechanism reveals that monolayer chemisorption of phosphate occurs on the MgO@SL/CMC CA through a ligand exchange process. The combination of favorable flexibility, green raw materials and superior phosphate capture performance endows MgO@SL/CMC CA with great application potential in the practical treatment of wastewater.

Removed heavy metal ions from wastewater reuse for chemiluminescence: Successive application of lignin-based composite hydrogels.

The novel sulfomethylated lignin-grafted-polyacrylic acid (SL-g-PAA) hydrogel was fabricated in this work via a facile and green synthetic strategy for the efficient removal of heavy metal ions from wastewater, and then successively reused for chemiluminescence (CL). The sulfomethylation of lignin was first performed to improve its water solubility and introduce numerous active sites for adsorption of heavy metal ions. The as-synthesized SL-g-PAA hydrogel with high content of lignin exhibited the highly efficient and rapid removal of various metal ions from simulated wastewater. More importantly, the spent hydrogel (M2+@SL-g-PAA) after adsorption was reused for the first time to develop a new CL system by an ingenious strategy, in which these metal ions adsorbed on M2+@SL-g-PAA act as heterogeneous catalytic sites to catalyze the CL reaction between N-(4-aminobutyl)-N-ethylisoluminol (ABEI) and H2O2. The resultant CL system displayed high CL intensity and long duration time, which could be observed by naked eye in the dark and lasted for > 24 h. The combination of facile fabrication process, renewable raw materials, and ingenious strategy for successive application in adsorption and CL endows this lignin-based composite hydrogel with a great potential for application in wastewater treatment, biological imaging and cold light sources.

Nitrogen-doped lignin-derived biochar with enriched loading of CeO2 nanoparticles for highly efficient and rapid phosphate capture.

Development of lignin-derived carbon adsorbents with ultrahigh phosphate adsorption activity and rapid adsorption kinetics is of great importance, yet limited success has been achieved. Herein, we develop a CeO2 functionalized N-doped lignin-derived biochar (Ce@NLC) via a cooperative modification strategy for effective and fast phosphate capture. The novel modification strategy not only contributes greatly to the loading of well-dispersed CeO2 nanoparticles with a smaller size, but also significantly increases the relative concentration of Ce(III) species on Ce@NLC. Consequently, an enhanced capture capacity for phosphate (196.85 mg g-1) as well as extremely rapid adsorption kinetics were achieved in a wide operating pH range (2-10). Interestingly, Ce@NLC exhibited a strong phosphate adsorption activity at even low-concentration phosphorus-containing water. The removal efficiency and final P concentration reached 99.87% and 2.59 µg P L-1 within 1 min at the phosphate concentration of 2 mg P L-1. Experiments and characterization indicated that Ce(III) species plays a predominant role for the phosphate capture, and ligand exchange, together with electrostatic attraction, are the main adsorption mechanism. This work develops not only an efficient carbon-based adsorbent for phosphate capture, but also promotes the high-value application of industrial lignin.

Recent advances and challenges on removal and recycling of phosphate from wastewater using biomass-derived adsorbents.

As the severe damage of phosphate enrichment in the water ecosystem and the supply shortage of phosphate rock, developing an efficient method for the removal and recycling of phosphate from wastewater is of great significance. To achieve this goal, adsorption technology has been widely investigated, and various adsorbents were developed. Among them, the biomass-derived adsorbents including biomass-derived carbon-based materials, biomass-based anion exchangers and metal-biomass composites have attracted increasing attention over the past years due to the low cost, abundant renewable raw materials and environmental friendliness. However, different adsorbents usually exhibit variable adsorption performances for phosphate, which highly depends on their design strategies, preparation methods and potential adsorption mechanisms. Thus, this review comprehensively summarizes the recent researches on the removal and recycling of phosphate from wastewater using the biomass-derived adsorbents. Especially, the design strategies, preparation methods, adsorption performances and mechanisms of these reported biomass-derived adsorbents are discussed in detail. Moreover, as the significant strategies to recover and recycling phosphate, the elution and direct use of phosphate-loaded adsorbents as fertilizers are also presented. Although the excellent adsorption performance has been obtained, some challenges are still existing, which should be given more attention in the following researches to facilitate the development and industrial application of biomass-derived adsorbents.

Enhanced adsorption activity for phosphate removal by functional lignin-derived carbon-based adsorbent: Optimization, performance and evaluation.

Design of carbon-based adsorbents derived from industrial lignin with superior phosphate adsorption performance is of great significance, yet limited researches have been reported. Here, we report a MgO-functionalized lignin-based bio-charcoal (MFLC) as an efficient adsorbent for phosphate removal. The obtained MgO nanoparticles were dispersed homogeneously on MFLC with particle size of 50-100 nm and higher loading content (28.41%). Benefiting from the favorable morphology of MgO nanoparticles, the MFLC exhibits excellent regeneration ability for phosphate adsorption, which can be applied in a wide range of pH values (2-10). The maximum adsorption capacity could reach to 906.82 mg g-1 for phosphate. Interestingly, the MFLC shows extremely high adsorption activity in the low concentration of phosphate (2 mg P L-1), and its phosphate removal efficiency achieves 99.76%. Furthermore, the results also indicated that the higher loading content of MgO together with smaller particle size can effectively enhance the phosphate adsorption activity of MFLC. The adsorption mechanism revealed that the adsorption of phosphate on the surface of MFLC belongs to single-layer chemisorption, and ligand exchange plays a crucial role during adsorption/desorption. This work not only develops a new strategy for the preparation of high-efficiency carbon-based adsorbents, but also facilitates the value-added utilization of industrial lignin.

Association of Serum Glucocorticoids with Various Blood Pressure Indices in Patients with Dysglycemia and Hypertension: the Henan Rural Cohort Study / 生物医学与环境科学（英文）

Objective@#To our knowledge, no definitive conclusion has been reached regarding the relationship between glucocorticoids and hypertension. Here, we aimed to explore the characteristics of glucocorticoids in participants with dysglycemia and hypertension, and to analyze their association with blood pressure indicators.@*Methods@#The participants of this study were from the Henan Rural Cohort study. A total of 1,688 patients 18-79 years of age were included in the matched case control study after application of the inclusion and exclusion criteria. Statistical methods were used to analyze the association between glucocorticoids and various indices of blood pressure, through approaches such as logistic regression analysis, trend tests, linear regression, and restricted cubic regression.@*Results@#The study population consisted of 552 patients with dysglycemia and hypertension (32.7%). The patients with co-morbidities had higher levels of serum cortisol ( @*Conclusions@#Serum deoxycortisol was positively correlated with systolic blood pressure, pulse pressure, mean arterial pressure, mean blood pressure, and mean proportional arterial pressure. Glucocorticoids (deoxycortisol and cortisol) increase the risk of hypertension in people with dysglycemia, particularly in those with T2DM.

Developmental relationship between mesenchymal stem/progenitor cells and hematopoietic cells during human embryogenesis / 中华微生物学和免疫学杂志

Objective@#To analyze the developmental relationship between mesenchymal stem/progenitor cells (MSPCs) and hematopoietic cells during human embryogenesis.@*Methods@#Aborted embryos at different developmental stages were used in this study after medical abortion. Embryonic blood tissues were isolated and digested into single cells. These single cells were plated in semisolid medium in favor of the differentiation of colony-forming cell with high proliferative potential (HPP-CFC) and incubated for 10 to 14 d. Individual colonies with diameter more than 0.5 mm were picked and replated in liquid medium. Fibroblastic adherent cells appeared in the replated colonies were cultured for cell proliferation and cytokins expressed on cell surface were identified to analyze whether they had the characteristics of MSPCs.@*Results@#This study summarized the dynamic development of HPP-CFCs and other hematopoietic progenitor cells in different tissues including aorta-gonad-mesonephros (AGM) region, yolk sac and embryonic liver. From the 28-somite stage, a proportion of HPP-CFCs in AGM region could give rise to adherent fibroblastic cells in addition to hematopoietic cells. The adherent cells harbored the differentiation potential of MSPCs and could inhibit the proliferation of T cells in lymphocyte transformation test.@*Conclusions@#This study suggests some prehematopoietic precursors in AGM region can give rise to both hematopoietic progenitors and MSPCs during human embryogenesis.

Small Solitary Ground-Glass Nodule on CT as an InitialManifestation of Coronavirus Disease 2019 (COVID-19)Pneumonia

The 2019 novel coronavirus (2019-nCoV) outbreak in Wuhan, Hubei Province, China in 2019 led to large numbers of peoplebeing infected and developing atypical pneumonia (coronavirus disease 2019, COVID-19). Typical imaging manifestations ofpatients infected with 2019-nCoV has been reported, but we encountered an atypical radiological manifestation on baselinecomputed tomography (CT) images in three patients from Wuhan, China infected with the 2019-nCoV. Surprisingly, the onlysimilar CT finding was a solitary sub-centimeter ground-glass nodule adjacent to bronchovascular bundles, which could beeasily overlooked. In addition, the follow-up images in these patients showed how COVID-19 pneumonia evolved from thesesmall nodules. The radiologic manifestation of the three cases will expand contemporary understanding of COVID-19.

Developmental relationship between mesenchymal stem/progenitor cells and hematopoietic cells dur-ing human embryogenesis / 中华微生物学和免疫学杂志

Objective To analyze the developmental relationship between mesenchymal stem/pro-genitor cells (MSPCs) and hematopoietic cells during human embryogenesis. Methods Aborted embryos at different developmental stages were used in this study after medical abortion. Embryonic blood tissues were isolated and digested into single cells. These single cells were plated in semisolid medium in favor of the dif-ferentiation of colony-forming cell with high proliferative potential ( HPP-CFC) and incubated for 10 to 14 d. Individual colonies with diameter more than 0. 5 mm were picked and replated in liquid medium. Fibroblastic adherent cells appeared in the replated colonies were cultured for cell proliferation and cytokins expressed on cell surface were identified to analyze whether they had the characteristics of MSPCs. Results This study summarized the dynamic development of HPP-CFCs and other hematopoietic progenitor cells in different tis-sues including aorta-gonad-mesonephros ( AGM) region, yolk sac and embryonic liver. From the 28-somite stage, a proportion of HPP-CFCs in AGM region could give rise to adherent fibroblastic cells in addition to hematopoietic cells. The adherent cells harbored the differentiation potential of MSPCs and could inhibit the proliferation of T cells in lymphocyte transformation test. Conclusions This study suggests some prehemato-poietic precursors in AGM region can give rise to both hematopoietic progenitors and MSPCs during human embryogenesis.

Amination of biorefinery technical lignin by Mannich reaction for preparing highly efficient nitrogen fertilizer.

To develop a novel lignin-based highly efficient nitrogen fertilizer, the amination of the biorefinery technical lignin was conducted by Mannich reaction synergy with phenolation pretreatment. Subsequently, the structural transformations of lignin samples and the reaction mechanism were investigated in detail. The soil column leaching experiment was also performed to research the nitrogen release behavior of aminated lignin in soil. The results indicated that the amounts of active sites in lignin were significantly increased to 8.26 mmol/g from the original 2.91 mmol/g by phenolation. In addition, the Mannich reaction was highly selective for occurring at ortho- and para-positions of phenolic hydroxyl groups in the phenolated lignin, in which the latter was favored. Moreover, the nitrogen content in the aminated lignin was highly depended on the types of amination reagent instead of the proportion of reactants in this study. Under an optimal condition, aminated lignin with a high nitrogen content (10.13%) and low C/N ratio (6.08) could be obtained. Besides, it was especially noteworthy that the prepared APL in this study has a favorable nitrogen release behavior in soil. Thus, it is believed that these aminated lignin derivatives could be used for the preparation of various lignin-based highly efficient nitrogen fertilizer.

Discordant lymphoma: report of one case and review of literature / 白血病·淋巴瘤

Objective@#To investigate the clinical characteristics, diagnosis, treatment and prognosis of discordant lymphoma.@*Methods@#The clinical data of one patient with discordant lymphoma at the PLA Strategic Support Force Characteristic Medical Center were retrospectively analyzed, and the related literatures were reviewed.@*Results@#The patient was treated for thrombocytopenia and the examination showed splenomegaly. After hormone treatment, the platelet rebounded and thrombocytopenia occurred during hormone reduction. Splenectomy was performed. Postoperative pathological diagnosis of splenic marginal lymphoma was made and observed. Axillary lymph node enlargement occurred nine months later. Pathological diagnosis of diffuse large B-cell lymphoma was made by using lymph node biopsy, and the disease condition was alleviated after immunotherapy combined with chemotherapy.@*Conclusions@#Discordant lymphoma is rare and shows no special clinical manifestations. Its diagnosis should rely on pathological examination. Immunotherapy combined with chemotherapy may be more effective.

Effects of Shengmai Jianghuang San on intestinal flora in nude mice with radio resistant cells of nasopharyngeal carcinoma / 中国中药杂志

Modern pharmacological studies have shown that Shengmai San has the effects of enhancing immunity and improving blood circulation, and Curcumae Longae Rhizoma(Jianghuang) has anti-inflammatory, anti-cancer, anti-oxidation and other functions. Shengmai San combined with Jianghuang is a new research direction in the study of anti-tumor of traditional Chinese medicines. The main treatment for nasopharyngeal carcinoma is radiation therapy, but radiation therapy can cause a variety of side effects, and it also changes the composition of the intestinal flora. In this study, the 16 s rDNA sequencing platform was used to perform macro-sequence sequencing of the intestinal flora samples of nude mice bearing the veins of Shengmai Jianghuang San, and then the results of intestinal flora data were analyzed to investigate the effect of Shengmai Jianghuang San on tumors. The results showed that Shengmai Jianghuang San combined with irradiation could enhance the therapeutic effect of tumor treatment. Radiation therapy would reduce the total number and diversity of intestinal flora in nude mice, and also change the structure of the flora. Shengmai Jianghuang San could protect the diversity of colonies, and also partially restore the colony imbalance caused by irradiation. This study provides a research idea for Shengmai Jianghuang San as a sensitizing adjuvant for radiotherapy of nasopharyngeal carcinoma.

Clinicopathologic and Prognostic Significance of the Zinc Finger of the Cerebellum Family in Invasive Breast Cancer / 한국유방암학회지

PURPOSE: Five members of the zinc finger of the cerebellum (ZIC) family—ZIC1, ZIC2, ZIC3, ZIC4, and ZIC5—have been shown to be involved in various carcinomas. Here, we aimed to explore the clinicopathologic and prognostic roles of ZIC family members in invasive breast cancer patients using immunohistochemical analysis, western blotting analysis, and real-time quantitative polymerase chain reaction (RT-qPCR). METHODS: A total of 241 female invasive breast cancer patients who underwent radical mastectomy between 2009 and 2011 were enrolled. ZIC proteins in 241 pairs of breast tumors and corresponding normal tissues were investigated using immunohistochemistry and the clinicopathologic roles of proteins were analyzed using Pearson's chi-square test. Kaplan-Meier curves and Cox regression analysis were also used to analyze the prognostic value of the ZIC proteins. In addition, 12 pairs of fresh-frozen breast tumors and matched normal tissues were used in the western blotting analysis and RT-qPCR. RESULTS: Only ZIC1 expression in normal tissues was obviously higher than that in tumors (p < 0.001). On multivariate analysis, ZIC1 expression (in overall survival analysis: hazard ratio [HR], 0.405, 95% confidence interval [CI], 0.233–0.702, p=0.001; in disease-free survival analysis: HR, 0.395, 95% CI, 0.234–0.669, p=0.001) was identified as a prognostic indicator of invasive breast cancer. CONCLUSION: ZIC1, but not the other proteins, was obviously decreased in breast tumors and associated with clinicopathologic factors. Thus, ZIC1 might be a novel indicator to predict the overall and disease-free survival of invasive breast cancer patients.

Small interfering RNA-mediated monocarboxylate transporter 1 silencing enhances sensitivity of nasopharyngeal carcinoma HNE1/DDP cells to cisplatin-induced apoptosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of small interfering RNA (siRNA)-mediated silencing of monocarboxylate transporter 1 (MCT1) on the sensitivity of drug-resistant nasopharyngeal carcinoma HNE1/DDP cells to cisplatin (DDP)-induced apoptosis and explore the possible mechanism.</p><p><b>METHODS</b>The expression of MCT1 was analyzed in HNE1 and HNE1/DDP cells and in HNE1/DDP cells transfected with siRNA using Western blot. MTT assay was used to assess the inhibitory effect of different concentrations of DDP alone or in combination with MCT1 siRNA on the proliferation of HNE1/DDP cells. The apoptosis of cells treated with MCT1 siRNA or/and DDP (8 µmol/L) was assessed using flow cytometry with PI staining, and the mitochondrial membrane potential was detected using JC-1 staining assay; the expressions of Mcl-1, Bak, Bcl-2, and Bax were analyzed using Western blotting.</p><p><b>RESULTS</b>HNE1/DDP cells showed a high expression of MCT1, and MCT1 silencing using siRNA significantly increased the sensitivity of HNE1/DDP cells to DDP (P<0.05) and partly reversed DDP resistance of the cells. MCT1 silencing enhanced the sensitivity of HNE1/DDP cells to DDP-induced apoptosis. Treatment of HNE1/DDP cells with MCT1 siRNA combined with 8 µmol/L DDP for 24 h resulted in an apoptotic rate of (51.23∓2.86)%, significantly higher than that in cells treated with MCT1 siRNA or DDP alone (P<0.05). The combined treatment also reduced the mitochondrial membrane potential, down-regulated the expression of Mcl-1 and Bcl-2, and up-regulated the expression of Bax in the DDP-resistant cells.</p><p><b>CONCLUSION</b>MCT1 siRNA can enhance the sensitivity of HNE1/DDP cells to DDP-induced apoptosis, the mechanism of which may involve the down-regulation of Mcl-1 and Bcl-2 and up-regulation of Bax expression.</p>

Regulatory mechanisms of gut microbiota on intestinal CYP3A and P-glycoprotein in rats with dextran sulfate sodium-induced colitis / 药学学报

As important constituents of the first-line of host defense barrier, intestinal cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) play important roles in disease pathogenesis as well as drug absorption and exposure. Clinical reports and experimental data revealed diminished intestinal CYP3A and P-gp expression accompanying with gut dysbiosis in inflammatory bowel disease. Yet whether gut dysbiosis is associated with the down-regulation of CYP3A and P-gp and the underlying mechanisms are unclear. In this study, daily administration of fresh feces from normal rats and rats with ulcerative colitis (UC) induced by dextran sulfate sodium to normal rats resulted in alterations of gut bacterial compositions. Intestinal CYP3A2 and P-gp were significantly down-regulated in rats receiving UC feces. Outer-membrane vesicles (OMVs) are nano-scale special buds of the outer membrane which are produced by Gram-negative bacteria and mediate diverse functions including interactions within bacterial communities and communications with host. Expressions of CYP3A4 and P-gp mRNA were diminished in human epithelial colorectal adenocarcinoma cells (Caco-2) treated by OMVs from all different groups with OMVs from UC rats or rats receiving UC feces showing more significant effects.Moreover, the OMVs fractions within 30 000-50 000 Daltons from both normal and UC rats elicited more effects than fractions of other molecular weights. Treatment of Caco-2 cells with toll like receptor 4 (TLR4) inhibitor resatorvid (TAK-242) or TLR4 silence RNA (siRNA) blocked CYP3A4 and P-gp down-regulation induced by bacterial OMVs. Taken together, we proved in this study that gut microbiota can down-regulate intestinal CYP3A and P-gp partially through producing OMVs to activate the TLR4 signaling pathway.