Pegylated-interferon alpha (PEG-IFNα)-induced interstitial lung disease in a patient with chronic hepatitis B: A case report and literature review.

OBJECTIVES: Interferon (IFN)-induced lung injury is a rare but severe complication. Studies are needed to elucidate the demographic characteristics, clinical manifestations, and prognostic features of IFN-induced interstitial lung disease (ILD). CASE REPORT: We report a patient with chronic hepatitis who developed ILD after interferon monotherapy. To further clarify the clinical characteristics of such patients, we searched for cases in which lung injury was documented as a side effect of hepatitis treatment and systematically analyzed all case reports for clinical manifestations, type of treatment, and outcomes. RESULTS: This is a 61-year-old male with a previous medical history of chronic hepatitis B. After 2 months of pegylated-interferon alpha (PEG-IFNα) application, he gradually developed cough and exertional dyspnea. Repeated chest images suggested progressive ILD, and lung biopsy revealed subacute lung injury. The diagnosis of PEG-IFNα-induced ILD was made. Including our case, 35 articles containing 45 patients were involved in our review. IFN-induced ILDs, often with a subacute onset, are characterized by nonproductive cough, dyspnea, and pulmonary infiltrates on chest radiograph. Most patients(62%, 28/45) required additional systemic steroid, and 5 (11%) patients who were co-administered ribavirin died of ILD progression despite steroid treatment. CONCLUSION: Although rare, IFN-induced ILD can lead to decreased lung function, and sometimes become fatal despite intensive treatment. Most previously reported cases were with chronic hepatitis C, and most of the medication was in combination with ribavirin. IFN-induced ILD should be monitored during IFN therapy, and appropriate steroid is recommended in patients with progressive manifestations.

EV71 infection induces neurodegeneration via activating TLR7 signaling and IL-6 production.

As a neurotropic virus, human Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease (HFMD) and may develop severe neurological disorders in infants. Toll-like receptor 7 (TLR7) acts as an innate immune receptor and is also a death receptor in the central nervous system (CNS). However, the mechanisms underlying the regulation of TLR7-mediated brain pathogenesis upon EV71 infection remain largely elusive. Here we reveal a novel mechanism by which EV71 infects astrocytes in the brain and induces neural pathogenesis via TLR7 and interleukin-6 (IL-6) in C57BL/6 mice and in human astroglioma U251 cells. Upon EV71 infection, wild-type (WT) mice displayed more significant body weight loss, higher clinical scores, and lower survival rates as compared with TLR7-/- mice. In the cerebral cortex of EV71-infected mice, neurofilament integrity was disrupted, and inflammatory cell infiltration and neurodegeneration were induced in WT mice, whereas these were largely absent in TLR7-/- mice. Similarly, IL-6 production, Caspase-3 cleavage, and cell apoptosis were significantly higher in EV71-infected WT mice as compared with TLR7-/- mice. Moreover, EV71 preferentially infected and induced IL-6 in astrocytes of mice brain. In U251 cells, EV71-induced IL-6 production and cell apoptosis were suppressed by shRNA-mediated knockdown of TLR7 (shTLR7). Moreover, in the cerebral cortex of EV71-infected mice, the blockade of IL-6 with anti-IL-6 antibody (IL-6-Ab) restored the body weight loss, attenuated clinical scores, improved survival rates, reduced the disruption of neurofilament integrity, decreased cell apoptotic induction, and lowered levels of Caspase-3 cleavage. Similarly, in EV71-infected U251 cells, IL-6-Ab blocked EV71-induced IL-6 production and cell apoptosis in response to viral infection. Collectively, it's exhibited TLR7 upregulation, IL-6 induction and astrocytic cell apoptosis in EV71-infected human brain. Taken together, we propose that EV71 infects astrocytes of the cerebral cortex in mice and human and triggers TLR7 signaling and IL-6 release, subsequently inducing neural pathogenesis in the brain.

Uptake of vegetable and soft drink affected transformation and bioaccessibility of lead in gastrointestinal track exposed to lead-contaminated soil particles.

Accidental ingestion of Pb-contaminated soil particles by direct hand-to-mouth activity or by swallowing airborne dust particles is important pathway of human exposure to Pb. Appropriate evaluation of Pb risk to human is important in determining whether the soil needs remediation or not, however, there is paucity of data about the dietary influences on Pb bioaccessibility (Pb-BA) and transformation in humans. This study chose two typical foods, spinach and cola, representing vegetable and soft drink, respectively, and investigated their effects on Pb species in gastrointestinal tract using the physiologically based extraction test. Results showed that ingestion of spinach and cola decreased the Pb-BA by 52%-94% in the gastric phase and by 38%-95% in the intestinal phase, respectively. The reduction of Pb-BA by spinach was attributed to the precipitation of Pb with phosphorus in spinach and the sorption of Pb by the generated hydrolysate and un-hydrolysate from spinach in gastrointestinal tract. Cola decreased Pb-BA mainly via formation of insoluble Pb phosphates precipitates. Analysis of X-ray diffraction and MINTEQ modeling demonstrated that the dissolved Pb was transformed to precipitated or sorbed Pb with intake of cola or spinach. Our findings suggest that dietary habit greatly influence the speciation and subsequent Pb-BA in the gastrointestinal tract, which should be incorporated into human health risk assessment of Pb-contaminated soil.

Electrospun nitrocellulose membrane for immunochromatographic test strip with high sensitivity.

The main goal of this work is to develop an economical, portable, disposable, and reliable point of care paper biosensor based on visualization, which can be used to detect viruses, bacteria, and proteins. However, the sensitivity of immunochromatography test (ICT) strips based on nitrocellulose to target detection has always been a problem. Here, we use an electrospun nitrocellulose (ENC) fiber membrane instead of traditional nitrocellulose fiber membrane to construct ICT strips for early pregnancy detection. By proper selection of the diameter of the ENC fiber to adjust the pore size, porosity, and morphology of the membrane, ICT strips with low flow rate and high protein loading were obtained. Based on these properties, a convenient and sensitive method for the colorimetric determination of human chorionic gonadotropin was developed. Under the optimal conditions, the detection limit of ICT based on ENC membrane is 10 mIU mL-1 (S/N = 3), the linear detection range is 5-1000 mIU mL-1, and the linear relationship is Y = 0.0434 X - 0.0136 (R2 = 0.9802). In addition, the test strip has good specificity and stability, and will not produce false-positive results. Graphical abstract.

Kinetics of antigen-specific IgM/IgG/IgA antibody responses during Zika virus natural infection in two patients.

Understanding of kinetics of antibody responses is crucial for developing rapid serological tests and studying the mechanisms of Zika virus (ZIKV) infection. Most of the serological diagnostic assays previously published are based on either IgM or IgG titer, little is known on the level of IgA antibody in saliva and urine. In this study, we investigated the kinetics of IgM/IgG/IgA antibody responses in serum, saliva, and urine obtained from two ZIKV infected individuals from as early as the second day of onset of symptoms to as long as 2 years postinfection. Other than detecting robust early IgM response, long lasting IgG response, we discovered strong early IgA response specific for ZIKV in saliva in both patients. This unique observation provides a novel strategy and scientific basis for the development of noninvasive rapid tests for ZIKV infection.

Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice.

BACKGROUND/AIMS: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells. METHODS: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods. RESULTS: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels. CONCLUSION: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model.

Genotoxic effects of old landfill leachate on HepG2 cells after nitration/ultrafiltration/reverse osmosis membrane treatment process.

Toxicity assessment of nitration/ultrafiltration/reverse osmosis (nitration/UF/RO) project, which has recently been widely used as an efficient process with applications in practical leachate treatment, was very limited. In the present study, DNA damage of leachates was investigated before and after the nitration/UF/RO process by a battery of assays with human hepatoma cells. Methyletrazolium assay showed a high cytotoxicity of 97.1% after being exposed to the highest concentration of raw leachate for 24 h, and a cytotoxicity of 26% in effluent at a concentration of 30% (v/v). Both comet assay (24 h) and γH2AX flow cytometer assay (3 h) showed increased levels of DNA damage in cells exposed to raw leachate and after nitration/UF-treated leachate followed by a significant increase of 7-ethoxyresorufin-O-deethylase activity. However, the effluent after nitration/UF/RO treatment showed no significant difference compared to negative control for γH2AX flow cytometer assay but slight DNA damage at concentrations of 20% and 30% (v/v) as well as increase of 7-ethoxyresorufin-O-deethylase. Analysis showed that nitration/UF/RO process exhibited high removal of physicochemical indexes and significant reduction of toxic and genotoxic effects of leachate, but still demands an improvement to reduce all possible negative risks to the environment and humans. Copyright © 2017 John Wiley & Sons, Ltd.

LC-UV Determination of Baicalin in Rabbit Plasma and Tissues for Application in Pharmacokinetics and Tissue Distribution Studies of Baicalin after Intravenous Administration of Liposomal and Injectable Formulations.

A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a reverse-phase C18 column with a gradient elution at flow rate of 1.0 mL/min. UV absorption was set at 278 nm. Chromatographic response was linear over the ranges of 0.05-10.00 µg/mL in plasma and 0.05-300.00 µg/g in tissues with the limits of quantification of 50.0 ng/mL in plasma and tissues, and the limit of detection of baicalin in bio-samples of 15 ng/mL. The RSD of intra-and inter-day for the biosamples were from 4.19% to 10.84% and from 4.37% to 10.93%, respectively. The accuracy of plasma and tissue samples ranged from 81.6% to 95.2% and 80.8% to 98.4%, respectively. The extraction recoveries ranged from 81.5% to 88.3% for plasma, from 73.1% to 93.2% for tissues, respectively. Baicalin was stable in rabbit biosamples. The validated method was successfully applied to the study of the pharmacokinetics and tissue distribution of baicalin after intravenous administration of liposomal and injectable formulations to rabbits. Compared to baicalin injection, the pharmacokinetics and biodistribution behavior of baicalin was altered significantly in rabbits treated with its liposomes and drug concentration in the lungs was greatly increased.

Optical nanoimaging for block copolymer self-assembly.

One approach toward optical nanoimaging involves sequential molecular localization of photoswitchable fluorophores to achieve high resolution beyond optical limit of diffraction. Block copolymer micelles assembled from polystryrene-block-poly(ethylene oxide) block copolymers (PSt-b-PEO) are visualized in optical nanoimaging by staining the polystyrene blocks with spiropyrans (SPs). SPs localized in hydrophobic phase of block copolymer micelles exhibit reversible fluorescence on-off switching at alternating irradiation of UV and visible light. Phase-selective distribution of SPs in block copolymer micelles enables optical nanoimaging of microphase structures of block copolymer self-assembly at 50-nm resolution. To date, this is the sturdiest realization of optical nanoimaging with subdiffraction resolution for solution self-assembly of block copolymers.

Ligand-directed stearic acid grafted chitosan micelles to increase therapeutic efficacy in hepatic cancer.

Targeted delivery system would be an interesting platform to enhance the therapeutic effect and to reduce the side effects of anticancer drugs. In this study, we have developed lactobionic acid (LA)-modified chitosan-stearic acid (CS-SA) (CSS-LA) to deliver doxorubicin (DOX) to hepatic cancer cells. The average particle size of CSS-LA/DOX was ∼100 nm with a high entrapment efficiency of >95%. Drug release studies showed that DOX release from pH-sensitive micelles is significantly faster at pH 5.0 than at pH 7.4. The LA conjugated micelles showed enhanced cellular uptake in HepG2 and BEL-7402 liver cancer cells than free drug and unconjugated micelles. Consistently, CSS-LA/DOX showed enhanced cell cytotoxicity in these two cell lines. Annexin-V/FITC and PI based apoptosis assay showed that the number of living cells greatly reduced in this group with marked presence of necrotic and apoptotic cells. LA-conjugated carrier induced typical chromatic condensation of cells; membrane blebbing and apoptotic bodies began to appear. In vivo, CSS-LA/DOX showed an excellent tumor regression profile with no toxic side effects. The active targeting moiety, long circulation profile, and EPR effect contributed to its superior anticancer effect in HepG2 based tumor. Our results showed that polymeric micelles conjugated with LA increased the therapeutic availability of DOX in the liver cancer cell based solid tumor without any toxic side effects. The active targeting ligand conjugated nanoparticulate system could be a promising therapeutic strategy in the treatment of hepatic cancers.

Attenuated acute salivary α-amylase responses to gustatory stimulation with citric acid in thin children.

Salivary α-amylase (sAA) is responsible for the 'pre-digestion' of starch in the oral cavity and accounts for up to 50 % of salivary protein in human saliva. An accumulating body of literature suggests that sAA is of nutritional importance; however, it is still not clear how sAA is related to individual's nutritional status. Although copy number variations (CNV) of the salivary amylase gene (AMY1) are associated with variation in sAA levels, a significant amount of sAA variation is not explained by AMY1 CNV. To measure sAA responses to gustatory stimulation with citric acid, we used sAA ratio (the ratio of stimulated sAA levels to those of resting sAA) and investigated acute sAA responses to citric acid in children with normal (Normal-BMI, n 22) and low (Low-BMI, n 21) BMI. The AMY1 gene copy number was determined by quantitative PCR. We, for the first time, demonstrated attenuated acute sAA responses (decreased sAA ratio) to gustatory stimulation in Low-BMI (thinness grade 3) children compared with the Normal-BMI children, which suggest that sAA responses to gustatory stimulation may be of nutritional importance. However, child's nutritional status was not directly related to their resting or stimulated sAA levels, and it was not associated with AMY1 gene copy number. Finally, AMY1 CNV might influence, but did not eventually determine, sAA levels in children.

Pharmacokinetic and tissue distribution of paclitaxel in rabbits assayed by LC-UV after intravenous administration of its novel liposomal formulation.

A simple, rapid and sensitive LC-UV method was developed and validated for the determination of paclitaxel (PTX) in rabbit plasma and tissues. A 2 mL aliquot of acetonitrile and 10 µL ammonium acetate (pH 5.0, 6 m) as extraction agents were used to markedly increase the extraction recoveries and greatly reduce the endogenous substances. The separation was achieved on a C18 column at 30 °C using an acetonitrile-ammonium acetate buffer (pH 5.0, 0.02 m; 55:45, v/v) at a flow rate of 1.0 mL/min; UV detection was used at 227 nm. Good linearity was obtained between 0.025 and 10,000 µg/mL for plasma and between 0.025-200,000 µg/g for tissue samples (r > 0.999). The limit of detection was 6 ng/mL in plasma, 8 ng/g in heart and 12.5 ng/g in other tissues. The limit of quantitation was 25 ng/mL in plasma and heart, 125 ng/g in other tissues. The intra- and inter-day assays of precision and accuracy for all bio-samples ranged from 1.38 to 9.60% and from 83.6 to 114.5%, respectively. The extraction recoveries ranged from 70.1 to 109.5%. Samples were stable during three freeze-thaw cycles or stored in a freezer at -20 °C for 30 days. The assay method was successfully applied to a study of the pharmacokinetics and tissue distribution of novel PTX lung targeting liposomes.

Passive lung-targeted drug delivery systems via intravenous administration.

The treatment of lung diseases including lung cancer and tuberculosis is one of the most challenging problems in clinical practice, because the conventional drug delivery systems cannot deliver drug effectively to the lung, which result in low therapeutic effect. Therefore, lung-targeted drug delivery systems (LTDDS) that can deliver drug to the lung in an effective way to increase drug concentration in lung tissue and reduce drug distribution in other organs and tissues become an ideal strategy to treat lung diseases. The LTDDS mainly include microparticles (microspheres and microencapsules), liposomes and nanoparticles via intravenous administration, and dry powder carriers and nebulized suspensions via pulmonary inhalation. As lungs possess the large absorptive surface area, the low thickness of the epithelial barrier and good blood supply, pulmonary inhalation has received great attention. Intravenous route is the commonly practiced method for administration of larger doses of drugs into the body. Numerous drugs can be delivered directly into general circulation by avoiding their first-pass metabolism and have potential to transport drugs to the lung via intravenous administration. This present article reviews the development, evaluation and application of LTDDS via intravenous administration for the treatment of lung diseases reported in the past decades.

Current progress and future perspective of microalgae biomass pretreatment using deep eutectic solvents.

Pretreatment process is considered as the most important step for effective microalgae biomass refining and has gained more interest since last decades. However, the main obstacles to commercialize microalgae products are recalcitrant cell wall and lack of cost-effective, green, and sustainable pretreatment approaches. Till now, various microalgae pretreatment approaches have been applied prior to extraction steps to enhance the accessibility of solvent inside the cells. However, high energy consumption and the hazardousness of solvents are considerable problem for these pretreatment methods. In this regard, deep eutectic solvents are recognized as sustainable and green solvents possessing great potential for microalgae biomass processing due to their low toxicity, low cost, biodegradability, easy recycling, and reuse. This article provides the fundamentals of DES composition, synthesis, properties, and the current advances in the application of microalgae biomass process.

Size-dependent influences of nanoplastics on microbial consortium differentially inhibiting 2, 4-dichlorophenol biodegradation.

Nanoplastics (NPs), as a type of newly emerging pollutant, are ubiquitous in various environmental systems, one of which is coexistence with organic pollutants in wastewater, potentially influencing the pollutants' biodegradation. A knowledge gap exists regarding the influence of microbial consortium and NPs interactions on biodegradation efficiency. In this work, a 2,4-dichlorophenol (DCP) biodegradation experiment with presence of polystyrene nanoplastics (PS-NPs) with particle sizes of 100 nm (PS100) or 20 nm (PS20) was conducted to verify that PS-NPs had noticeable inhibitory effect on DCP biodegradation in a size-dependent manner. PS100 at 10 mg/L and 100 mg/L both prolonged the microbial stagnation compared to the control without PS-NPs; PS20 exacerbated greater, with PS20 at 100 mg/L causing a noticeable 6-day lag before the start-up of rapid DCP reduction. The ROS level increased to 1.4-fold and 1.8-fold under PS100 and PS20 exposure, respectively, while the elevated LDH under PS20 exposure indicated the mechanical damage to cell membrane by smaller NPs. PS-NPs exposure also resulted in a decrease in microbial diversity and altered the niches of microbial species, e.g., they decreased the abundance of some functional bacteria such as Brevundimonas and Comamonas, while facilitated some minor members to obtain more proliferation. A microbial network with higher complexity and less competition was induced to mediate PS-NPs stress. Functional metabolism responded differentially to PS100 and PS20 exposure. Specifically, PS100 downregulated amino acid metabolism, while PS20 stimulated certain pathways in response to more severe oxidative stress. Our findings give insights into PS-NPs environmental effects concerning microflora and biological degradation.

A comprehensive study of the colloidal properties, biocompatibility, and synergistic antioxidant actions of Antarctic krill phospholipids.

Excipient selection is crucial to address the oxidation and solubility challenges of bioactive substances, impacting their safety and efficacy. AKPL, a novel ω-3 polyunsaturated fatty acids (PUFAs) esterified phospholipid derived from Antarctic krill, demonstrates unique antioxidant capabilities and synergistic effects. It exhibits pronounced surface activity and electronegativity at physiological pH, as evidenced by a critical micelle concentration (CMC) of 0.15 g/L and ζ-potential of -49.9 mV. In aqueous environments, AKPL self-assembles into liposomal structures, offering high biocompatibility and promoting cell proliferation. Its polyunsaturated bond-rich structure provides additional oxidation sites, imparting antioxidant properties superior to other phospholipids like DSPC and DOPC. Additionally, AKPL augments the efficacy of lipophilic antioxidants, such as alpha-tocopherol and curcumin, in aqueous media through both intermolecular and intramolecular interactions. In sum, AKPL emerges as an innovative unsaturated phospholipid, offering new strategies for encapsulating and delivering oxygen-sensitive agents.

Increased intestinal bile acid absorption contributes to age-related cognitive impairment.

Cognitive impairment in the elderly is associated with alterations in bile acid (BA) metabolism. In this study, we observe elevated levels of serum conjugated primary bile acids (CPBAs) and ammonia in elderly individuals, mild cognitive impairment, Alzheimer's disease, and aging rodents, with a more pronounced change in females. These changes are correlated with increased expression of the ileal apical sodium-bile acid transporter (ASBT), hippocampal synapse loss, and elevated brain CPBA and ammonia levels in rodents. In vitro experiments confirm that a CPBA, taurocholic acid, and ammonia induced synaptic loss. Manipulating intestinal BA transport using ASBT activators or inhibitors demonstrates the impact on brain CPBA and ammonia levels as well as cognitive decline in rodents. Additionally, administration of an intestinal BA sequestrant, cholestyramine, alleviates cognitive impairment, normalizing CPBAs and ammonia in aging mice. These findings highlight the potential of targeting intestinal BA absorption as a therapeutic strategy for age-related cognitive impairment.

A broadly applicable protein-polymer adjuvant system for antiviral vaccines.

Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and cellular immunity and the need for vaccine adjuvants and delivery system. Herein, we assess a vaccine adjuvant system comprising Quillaja Saponaria-21(QS-21) and cobalt porphyrin polymeric micelles that enabling the display of His-tagged antigen on its surface. The nanoscale micelles promote antigen uptake and dendritic cell activation to induce robust cytotoxic T lymphocyte response and germinal center formation. Using the recombinant protein antigens from influenza A and rabies virus, the micelle adjuvant system elicited robust antiviral responses and protected mice from lethal challenge. In addition, this system could be combined with other antigens to induce high titers of neutralizing antibodies in models of three highly pathogenic viral pathogens: Ebola virus, Marburg virus, and Nipah virus. Collectively, our results demonstrate this polymeric micelle adjuvant system can be used as a potent nanoplatform for developing antiviral vaccine countermeasures that promote humoral and cellular immunity.

[Synthesis and experimental study of a novel polymer/gene compound drug controlled release system for the treatment of erectile dysfunction].

OBJECTIVE: To overcome the deficiency in the current therapies for erectile dysfunction (ED), we designed and synthesized a novel high-efficiency polymer/gene compound drug controlled release system and discussed the feasibility of pH and temperature dually sensitive injectable hydrogel in ED gene therapy. METHODS: We synthesized optimal siRNA gene nanoparticles by characterizing the zeta potential of polylysine (PLL)/siRNA gene compounds, and established a pH and temperature dually sensitive injectable gene compound drug controlled release system via Schiffs reaction between glycol chitosan (GC) and benzaldehyde capped OHC-PEO-PPO-PEO-CHO. Then we demonstrated the sustained release of the system at different temperatures. RESULTS: When the mass ratio of PLL to siRNA was 20:1, the zeta potential of the PLL/siRNA gene compound reached the peak (+23.5 mV) and the siRNA was encapsulated by PLL in the maximal degree. GC and OHC-PEO-PPO-PEO-CHO was crosslinked via benzoicimine reaction when environmental pH was changed from 5.5 to 7.4. The reslease of the siRNA encapsulated in this system kept at a low rate at 37 degrees C, significantly enhanced with the increase of the temperature to 60 degrees C, rising to (122.5 +/- 5.3) microg at 1 000 minutes as compared with (23.8 +/- 6.0) microg at 37 degrees C (P < 0.05). CONCLUSION: The polymer/gene compound drug controlled release system was successfully synthesized, which improved the stability and capacity of gene carriers and achieved siRNA release at different temperatures, promising to be a new approach to the gene therapy of ED.

[Research Progress on Trojan-horse Effect of Microplastics and Heavy Metals in Freshwater Environment].

As an emerging pollutant of global concern, microplastics (plastics with size<5 mm) and heavy metals are widely found in freshwater environments. Microplastics migrate easily, are difficult to degrade, and have large specific surface areas. They can enrich a variety of pollutants such as heavy metals and greatly increase their potential harm to the environment and ecology. Firstly, the special environmental behavior of microplastics carrying heavy metals and migrating together in freshwater environments was defined as the "Trojan-horse effect." Then, the Trojan-horse effect and its mechanism of microplastics and heavy metals in the freshwater environment were summarized and expounded from four aspects:the source and distribution of microplastics in the freshwater environment, the enrichment effect of microplastics on heavy metals, the impact of microplastics and the heavy metal Trojan-horse effect on its migration behavior, and the biological impact of microplastics and the heavy metal Trojan-horse effect. The results showed that, as a wide range of non-point source pollutants, microplastics widely existed in freshwater environments. In freshwater environments, the adsorption degree of single metals was different in different environments. It was mainly affected by microplastics, metals, and environmental factors. There was competitive adsorption in the presence of multiple metal ions. The Trojan-horse effect of microplastics and heavy metals could also affect their co-transport behavior. The Trojan-horse effect of microplastics and heavy metals in the freshwater environment frequently exacerbated their toxicity to aquatic organisms. This study provides references for comprehensively understanding the Trojan-horse effect and its mechanism in microplastics and heavy metals in the freshwater environment, which could effectively reduce the ecological risk and impact on human health of microplastics and heavy metals in the freshwater environment.