[Analysis of a Chinese pedigree affected with Spinal muscular atrophy due to compound heterozygous variants of SMN gene].

OBJECTIVE: To analyze variants of SMN gene in a Chinese pedigree affected with Spinal muscular atrophy (SMA). METHODS: A Chinese pedigree diagnosed at the Nanchang First Hospital in January 2020 was selected as the study subject. Peripheral blood samples were collected for the extraction of DNA. All exons of the SMN gene were detected by multiple ligation-dependent probe amplification (MLPA). Potential variants of the SMN gene were also detected by Whole exome sequencing (WES), and the result was verified by Sanger sequencing. cDNA extracted from fresh blood sample was used as a template to verify the location of variant on the SMN genes. RESULTS: The proband was found to harbor a heterozygous deletion of the SMN1 Exon7+Exon8, and a heterozygous c.81G>A variant. The SMN1 Exon7+Exon8 deletion was inherited from her father and grandmother, whilst the c.81G>A variant was inherited from her mother and maternal grandfather. Her aunt was also a carrier of the heterozygous deletion, while her paternal aunt, her husband, and their daughter were not. cDNA amplification and Sanger sequencing confirmed that the c.81G>A variant was located in the SMN1 gene. CONCLUSION: MLPA combined with NGS and Sanger sequencing can identify compound heterozygous variants of the SMN gene in the SMA patients.

Cluster analysis of clinical phenotypic heterogeneity in obstructive sleep apnea assessed using photoplethysmography.

BACKGROUND: We evaluated heterogeneity in clinical phenotypes among patients with obstructive sleep apnea syndrome (OSAHS) using photoplethysmography (PPG) in cluster analysis. METHODS: All enrolled patients underwent polysomnography (PSG) monitoring while wearing a PPG device. Pulse wave signals were recorded with a modified pulse oximetry probe in the PPG device. The pulse wave-derived cardiac risk composite parameter (CRI) and eight derived signal parameters were used to assess OSAHS phenotype. We defined a high cardiovascular risk OSAHS group (CRI ≥0.5) and low cardiovascular risk OSAHS group (CRI <0.5). K-means clustering was performed for analysis of clinical phenotype heterogeneity in OSAHS by combining the CRI and its derived signals. RESULTS: The OSAHS group had high cardiovascular risk for sex, age, body mass index, systolic and diastolic blood pressure, apnea hypopnea index, and obstructive arousal index and higher risk of developing hypertension, diabetes, and cerebrovascular comorbidities. The low cardiovascular risk OSAHS group had higher blood oxygen levels. Three clinical phenotypes were identified in CRI clustering: 1) typical OSAHS with high risk of hypertension (characterized by middle age, obesity, hypertension with severe OSAHS); 2) older women and mild OSAHS; 3) older men and mild OSAHS. Three subtypes were obtained based on the eight cardiac risk-derived parameters: 1) hypoxia combined with decreased pulse wave amplitude variation; 2) decreased vascular pulse wave amplitude combined with decreased pulse frequency; 3) arrhythmia combined with hypoxia. CONCLUSIONS: Establishing OSAHS clinical phenotypes with the CRI and derived parameters using PPG may help in establishing multi-dimensional assessment of cardiovascular risk in OSAHS.

Efficient degradation of naproxen in a three dimensional biofilm electrode magnetism reactor (3DBEMR): Removal performance and microbial community.

A three-dimensional biofilm electrode magnetism reactor (3DBEMR) was constructed to removal naproxen (NPX). This study evaluated 3DBEMR performance in removal of refractory NPX, while also discussing the effect of the electro-magnetic superposition on microbial community by high throughput sequencing. Results indicated that 3DBEMR's average removal rate for NPX stood at 88.36%, representing an increase by 75.24%, 65.03% and 12.36%, respectively, compared to 3DBR (Three-Dimensional Biofilm Reactor), 3DBMR (Three-Dimensional Biofilm Magnetism Reactor) and 3DBER (Three-Dimensional Biofilm Electrode Reactor). This was attributed to the influence of electro-magnetic adsorption, electro-oxidaton/catalysis, and electro-magnetic biodegradation. Another major contributing factor to NPX removal was the presence in 3DBEMR of high-abundance genera such as Rhodobacter, Porphyrobacter, Methyloversatilis, Sphingopyxis,Bosea, Singulisphaera, Sphingomonas. Therefore, the 3DBEMR was successfully demonstrated to be a flexible and effective technique in NPX degradation, which would help to better understand the effect of superposition of electric and magnetic fields on microbial community.

Electro/magnetic superposition effects on diclofenac degradation: Removal performance, kinetics, community structure and synergistic mechanism.

Electric and magnetic fields characterized by high efficiency, low consumption and environment-friendly performance have recently generated interest as a possible measure to enhance the performance of the biological treatment process used to remove refractory organics. Few studies have been carried out to-date regarding the simultaneous application of electric and magnetic fields on biofilm process to degrade diclofenac. In this study, 3DEM-BAF was designed to evaluate the electrio-magnetic superposition effect on diclofenac removal performance, kinetics, community structure and synergistic mechanism. The results show that 3DEM-BAF could significantly increase the average removal rate of diclofenac by 65.30 %, 57.46 %, 9.48 % as compared with that of BAF, 3DM-BAF, 3DE-BAF, respectively. The diclofenac degradation kinetic constants and dehydrogenase activity of 3DEM-BAF were almost 6.72 and 2.53 times higher than those of BAF. Microorganisms of 3DEM-BAF in the Methylophilus and Methyloversatilis genera were distinctively enriched, which was attributed to the screening function of electric field and propagation effect of magnetic field. Moreover, three processes were found to contribute to diclofenac degradation, namely electro-magnetic-adsorption, electro-chemical oxidation and electro-magnetic-biodegradation. Thus, the simultaneous application of electric and magnetic fields on biofilm process was demonstrated to be a promising technique as well as a viable alternative in diclofenac degradation enhancement.

Production of an electro-biological particle electrode (EBPE) from lithium slag and its removal performance to salicylic acid in a three-dimensional electrocatalytic biological coupling reactor (3D-EBCR).

Electro-biological particle electrode (EBPE) prepared by lithium slag was used to remove salicylic acid in a three-dimensional electrocatalytic biological coupling reactor (3D-EBCR). The physical and chemical properties of the EBPE, the removal performance of salicylic acid and the degradation mechanism were studied. Results revealed as follows: (1) the EBPE prepared by lithium slag contained effective catalytic components including Fe2O3, SnO2, ZnO, MnO, Rb2O and TiO2, with stable structure and good adsorption performance; (2) the 3D-EBCR with EBPE had strong adaptability to the current intensity in the range of 0.25-0.40 A, and the removal rates of COD and salicylic acid were maintained above 87.1% and 85.2% respectively; (3) salicylic acid was removed through the synergistic action of adsorption, electrochemical oxidation and biological action.

Accelerated Rhodamine B removal by enlarged anode electric biological (EAEB) with electro-biological particle electrode (EPE) made from steel converter slag (SCS).

Electro-biological particle electrode (EPE) made from steel converter slag (SCS) was used as a particle electrode in an enlarged anode electric biological (EAEB) reactor for Rhodamine B (RhB) wastewater treatment, and its purification performance and microbial community were examined. The results revealed that (1) the EAEB reactor showed much higher average removal rates of RhB, COD and NH4+-N, i.e. 91.68%, 87.63%, and 90.54%, which meant an increase by 59.86%, 20.48%, and 14.22%, respectively, compared with BAF; (2) The optimum current intensity (CI) for simultaneously removing RhB, COD and NH4+-N in the EAEB reactor was at 1.00 A; and (3)Methylophilus, Aeromonas, Pseudomonas, Pelomonas and Zoogloea accounted for the main bacterial community in EAEB. Therefore, the EAEB reactor with EPE produced from steel converter slag (SCS) was suitable to simultaneously remove RhB, COD and NH4+-N.

Removal of diclofenac by three-dimensional electro-Fenton-persulfate (3D electro-Fenton-PS).

Diclofenac (DIC) is a new type of contaminant that has been widely detected in the water environment, posing threats to the ecological environment and human health. However, the conventional wastewater treatment process has a very limited ability to reduce DIC. In this research, persulfate is added to electro-Fenton with the three-dimensional particle electrode (TDE) process whose particle electrodes were formed from manganese slag with loaded active substance (Cu: Fe = 1:1) to construct a three-dimensional electro-Fenton-persulfate (3D electro-Fenton-PS) process to investigate the removal rate of DIC under the optimum working conditions. The effects of different persulfate addition, activator addition and different activators on the removal rate of DIC were researched, respectively. The removal rate of DIC reached 96.3% when the persulfate and the Fe0 addition were 1.50 mM and 3.00 mM, respectively. The results showed that and OH existed simultaneously in the reaction system, and the removal of DIC was the result of the two free radicals. Moreover, degradation pathways and mechanism of DIC were also discussed. The study may provide a new theoretical basis and technical support for the treatment of DIC in municipal wastewater.

Protective effects and active ingredients of Salvia miltiorrhiza Bunge extracts on airway responsiveness, inflammation and remodeling in mice with ovalbumin-induced allergic asthma.

BACKGROUND: Salvia miltiorrhiza Bunge (S. miltiorrhiza), a traditional Chinese medicine, has demonstrated antioxidant, anti-inflammatory, and antibacterial activities. However, its effects against asthma that shows chronic inflammation and oxidative damage remain unknown. PURPOSE: To assess the effects of S. miltiorrhiza extracts on airway responsiveness, inflammation, and remodeling in ovalbumin (OVA)-induced asthmatic mice. METHODS: Mice with ovalbumin (OVA)-induced allergic asthma were treated with S. miltiorrhiza extracts, and airway resistance (RL) to methacholine, inflammatory cell infiltration, Th1/Th2 cytokine levels, and airway remodeling were assessed. TGF-ß1-induced BEAS-2B and MRC-5 cells were used to evaluate the effects of five S. miltiorrhiza compounds on epithelial-mesenchymal transition and fibrosis. RESULTS: OVA-challenge resulted in remarkably increased RL, inflammatory cell infiltration, Th1/Th2 cytokine levels in BALF, goblet cell hyperplasia, collagen deposition, and airway wall thickening. Daily treatment with S. miltiorrhiza ethanolic (EE, 246 mg/kg) or water (WE, 156 mg/kg) extract significantly reduced OVA-induced airway inflammatory cell infiltration, Th1/Th2 cytokine amounts, and goblet cells hyperplasia. However, only WE remarkably decreased RL, collagen deposition, and airway wall thickening. Moreover, Chromatography showed that salvianic acid A and caffeic acid levels were much higher in WE than EE, while rosmarinic acid was slightly lower; salvianolic acid B and tanshinone IIA levels were much higher in EE than WE. Interestingly, caffeic acid and rosmarinic acid were more potent in reducing E-cadherin and vimentin levels in TGF-ß1-induced BEAS-2B cells, and α-SMA and COL1A1 amounts in TGF-ß1-induced MRC-5 cells. CONCLUSIONS: Both S. miltiorrhiza WE and EE alleviate airway inflammation in mice with OVA-sensitized allergic asthma. S. miltiorrhiza WE is more potent in reducing responsiveness and airway remodeling.

In-situ ion exchange electrocatalysis biological coupling (i-IEEBC) for simultaneously enhanced degradation of organic pollutants and heavy metals in electroplating wastewater.

The goal of this research was to develop a new process for simultaneously removing organics and heavy metals of electroplating wastewater by in-situ ion exchange electrocatalysis biological coupling (i-IEEBC). The study evaluated the removal efficiency of coexisting refractory organics and heavy metal ions, and investigated the effects of current density (CD) on the removal performance of the i-IEEBC method. The results indicated the i-IEEBC reactor exhibited higher average removal rates of COD, TOC, Cr and Cu ions, i.e. 87.23%, 80.42%, 91.25%, and 95.97% in that order, which represented an increase by 32.59%, 40.10%, 31.86%, and 33.82%, respectively, compared with BAF. The optimum CD for simultaneously removing organics and heavy metals of electroplating wastewater in i-IEEBC was 0.40 mA/(cm)2. The change of biodegradability and the presence of short chain organic compounds also indirectly confirmed the excellent removal organic pollutants performance of i-IEEBC at the optimum CD. In addition, the composition and construction of CER before and after the application, under the optimum CD, SEM, EDS and FT-IR spectroscopy also showed that the cation exchange properties of CER improved the catalytic lifetime of the particle electrodes. This research provides a highly efficient new alternative to electroplating wastewater treatment technology.

Performance and microbial community of an electric biological integration reactor (EBIR) for treatment of wastewater containing ibuprofen.

Electric biological integration reactor (EBIR) was designed and built for the treatment of wastewater containing ibuprofen. This study evaluates the removal performance of EBIR by comparison with biological aerated filter (BAF), while also discussing the optimal operational parameters of EBIR within the context of the response surface methodology. The results indicate that EBIR exhibits higher average removal rates of ibuprofen, chemical oxygen demand (COD) and NH4+-N, i.e. 93.48%, 86.72% and 85.19%, representing an increase by 61.59%, 14.57% and 10.49%, respectively, compared with BAF. The optimal conditions for EBIR were 12.73 A/m2 current density (CD), 3.5 h hydraulic retention time and 0.08 mg/L influent ibuprofen concentration. In addition, microbial community structures were detected using an Illumina Miseq PE300 system, which were different at the phylum, class, and genus levels between EBIR and BAF. The microbial communities of EBIR, including mainly Trichococcus, Aeromonas, Saprospiraceae_uncultured, Thiobacillus, Aeromonas Flavobacterium, Sphingopyxis, Candidate_division_TM7_norank, Acinetobacter and physicochemical properties indirectly confirmed the excellent removal performance at 12.73 A/m2 CD.

Preparation of particle electrodes from manganese slag and its degradation performance for salicylic acid in the three-dimensional electrode reactor (TDE).

Salicylic acid (SA) is a class of trace pollutants widely presented in the environment belonged to pharmaceuticals and personal care products. It is difficult to remove SA by the traditional treatment processes because of its toxicity. In this paper, the degradation of SA by Mn-loaded Cu/Fe particle electrodes was studied. Firstly, the particle electrodes were prepared by impregnation-roasting method and then characterized by SEM, XRF and XRD. The diffraction peaks of Fe2O3 and CuO in the XRD patterns of the particle electrodes which had the dense spherical particles were significantly increased and the content of CuO and Fe2O3 increased by 1.9% and 3.6% respectively. Secondly, single factor experiments were carried out under conditions of cell voltage, electrolyte concentration, pH, HRT, inter-electrode distance and initial pollutant concentration. Under the optimum conditions of all the factors, the degradation rate of SA reached 76.9%. Then, HPLC and GCMS were employed to deduce the degradation pathways of SA by the TDE with Mn-particle electrodes (Mn-PETDE). Under the action of •OH, SA underwent decarboxylation and substitution reactions and then mineralized after the ring-opening reaction. All results demonstrated that this Mn-PETDE was effective for degradation of SA.

Inducible epitope imprinting: 'generating' the required binding site in membrane receptors for targeted drug delivery.

We report an inducible epitope imprinting strategy that as a template, a flexible peptide chain can have a disordered-to-ordered conformational change by suitable inducement through a molecular imprinting procedure, and the formed nanoparticles can, in turn, remold the original peptide into the expected conformation and specifically bind to the corresponding protein.

[Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy].

In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy.

Construction of a two-in-one liposomal system (TWOLips) for tumor-targeted combination therapy.

In oncology, there is a growing need for simpler, more selective methods to deliver drug therapies directly to the tumor site. For combination therapies, simultaneous targeted delivery of multiple drugs would represent a significant improvement. In contrast to previous work that took a de novo approach, we constructed a novel two-in-one liposomal system (TWOLips) from two single drug-loaded liposomes. Our results demonstrated that TWOLips could be prepared by a simple process, through silica coating of one liposome and incubation with the second liposome. TWOLips had a mean diameter of 100 nm, relatively high drug loading rates (96.8%±0.9% for doxorubicin and 78.4%±1.2% for combretastatin), and high storage stability. TWOLips modification by adding a targeting moiety, an all D-amino acid peptide derived from a natural vascular endothelial growth factor, resulted in strong, selective binding to vascular endothelial growth factor receptor 2, a tumorigenesis marker, in vitro and in vivo. TWOLips significantly inhibited tumor growth and angiogenesis and enhanced survival in mice with A375 melanoma xenografts. The TWOLips system had a low potential risk of toxicity. Since the stepwise assembly could be carried further (additional drug-loaded liposomes), TWOLips shows potential as a treatment for many cancers, especially those that require multiple drugs.

Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin.

We investigated flexible liposomes as a potential oral drug delivery system. However, enhanced membrane fluidity and structural deformability may necessitate liposomal surface modification when facing the harsh environment of the gastrointestinal tract. In the present study, silica-coated flexible liposomes loaded with curcumin (CUR-SLs) having poor water solubility as a model drug were prepared by a thin-film method with homogenization, followed by the formation of a silica shell by the sol-gel process. We systematically investigated the physical properties, drug release behavior, pharmacodynamics, and bioavailability of CUR-SLs. CUR-SLs had a mean diameter of 157 nm and a polydispersity index of 0.14, while the apparent entrapment efficiency was 90.62%. Compared with curcumin-loaded flexible liposomes (CUR-FLs) without silica-coatings, CUR-SLs had significantly higher stability against artificial gastric fluid and showed more sustained drug release in artificial intestinal fluid as determined by in vitro release assays. The bioavailability of CUR-SLs and CUR-FLs was 7.76- and 2.35-fold higher, respectively, than that of curcumin suspensions. Silica coating markedly improved the stability of flexible liposomes, and CUR-SLs exhibited a 3.31-fold increase in bioavailability compared with CUR-FLs, indicating that silica-coated flexible liposomes may be employed as a potential carrier to deliver drugs with poor water solubility via the oral route with improved bioavailability.