Light-Controlled Regulation of Dual-Enzyme Properties in YbGd-Carbon Quantum Dots Nano-Hybrid for Advanced Biosensing.

Compared to nanozymes with single enzyme activity, those with multiple enzyme activities possess broader application potential due to their diversified enzymatic functionalities. However, the multienzyme nanozymes currently face challenges of interference among different enzymatic activities during practical applications. In this study, we report the synthesis of a light-responsive YbGd-carbon quantum dots nano-hybrid, termed YbGd-CDs, which exhibits controllable enzyme-mimicking activities. This light-responsive behavior enables selective control of the enzymatic activities. Under visible light irradiation, YbGd-CDs demonstrate robust oxidase-like activity. Conversely, under dark conditions, they primarily exhibit peroxidase-like activity. Leveraging the dual-enzyme-mimicking capabilities of YbGd-CDs, we developed colorimetric assays for sensitive detection of total antioxidant capacity (TAC) in both normal and cancer cells as well as d-amino acids in human saliva. This study not only advances the synthesis of carbon-based nanozymes but also highlights their potential in biosensing applications.

An atypical case of incontinentia pigmenti with a hypomorphic variant.

Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis that affects skin, hair, teeth, eyes and central nervous system. We present the case of a female patient with mild IP caused by a hypomorphic pathogenic variant of the inhibitor of the kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG) gene. This is the first report of a female IP patient with the hypomorphic variant, NM_001099856.6: c.1423dup, which is causative of anhidrotic ectodermal dysplasia with immune deficiency in males.

The effect of polystyrene nanoplastics on arsenic-induced apoptosis in HepG2 cells.

Microplastics are detrimental to the environment. However, the combined effects of microplastics and arsenic (As) remain unclear. In this study, we investigated the combined effects of polystyrene (PS) microplastics and As on HepG2 cells. The results showed that PS microplastics 20, 50, 200, and 500 nm in size were taken up by HepG2 cells, causing a decrease in cellular mitochondrial membrane potential. The results of lactate dehydrogenase release and flow cytometry showed that PS microplastics, especially those of 50 nm, enhanced As-induced apoptosis. In addition, transcriptome analysis revealed that TP53, AKT1, CASP3, ACTB, BCL2L1, CASP8, XIAP, MCL1, NFKBIA, and CASP7 were the top 10 hub genes for PS that enhanced the role of As in HepG2 cell apoptosis. Our results suggest that nano-PS enhances As-induced apoptosis. Furthermore, this study is important for a better understanding of the role of microplastics in As-induced hepatotoxicity.

Computer-aided optimization of carbidopa/levodopa orally disintegrating tablets.

OBJECTIVE: This study aimed to optimize the formulation of carbidopa/levodopa orally disintegrating tablets (ODTs) in order to improve their disintegration performance, and facilitate easier medication intake for Parkinson's patients. METHOD: The response surface methodology (RSM) was used to optimize the formulation, with the content of cross-linked polyvinylpyrrolidone (PVPP), microcrystalline cellulose (MCC), and mannitol (MNT) as independent variables, and disintegration time as the response parameter. Python was utilized to model Carr Indices and mixing time to determine the suitable mixing time. Direct compression (DC) was used for the preparation of ODTs. RESULT: The optimization process resulted in the following values for the independent variables: 7.04% PVPP, 22.02% MCC, and 16.21% MNT. By optimizing the mixing time using Python, it was reduced to 14.19 min. The ODTs prepared using the optimized formulation and a mixing time of 14.19 min exhibited disintegration times of 16.74 s in vitro and 17.63 s in vivo. The content uniformity of levodopa and carbidopa was found to be 100.83% and 99.48%, respectively. CONCLUSION: The ODTs optimized using RSM and Python demonstrated excellent disintegration performance, leading to a decrease in the time the drug exists in solid form in the oral cavity. This improvement in disintegration time reduced the difficulty of swallowing for patients and enhanced medication compliance, while still ensuring that ODTs prepared by DC had sufficient mechanical strength to meet storage and transportation requirements.

Harnessing Self-Repairing and Crystallization Processes for Effective Enzyme Encapsulation in Covalent Organic Frameworks.

Immobilization of fragile enzymes in crystalline porous materials offers new opportunities to expand the applications of biocatalysts. However, limited by the pore size and/or harsh synthesis conditions of the porous hosts, enzymes often suffer from dimension limitation or denaturation during the immobilization process. Taking advantage of the dynamic covalent chemistry feature of covalent organic frameworks (COFs), herein, we report a preprotection strategy to encapsulate enzymes in COFs during the self-repairing and crystallization process. Enzymes were first loaded in the low-crystalline polymer networks with mesopores formed at the initial growth stage, which could offer effective protection for enzymes from the harsh reaction conditions, and subsequently the encapsulation proceeded during the self-repairing and crystallization of the disordered polymer into the crystalline framework. Impressively, the biological activity of the enzymes can be well-maintained after encapsulation, and the obtained enzyme@COFs also show superior stability. Furthermore, the preprotection strategy circumvents the size limitation for enzymes, and its versatility was verified by enzymes with different sizes and surface charges, as well as a two-enzyme cascade system. This study offers a universal design idea to encapsulate enzymes in robust porous supports and holds promise for developing high-performance immobilized biocatalysts.

Detection of microplastics in domestic and fetal pigs' lung tissue in natural environment: A preliminary study.

Microplastics (MPs) are ubiquitous in the environment. However, it is unclear whether MPs are present in mammalian lungs through inhalation, and if so, could be possibly found in fetal tissues. In this study, we aim to determine the presence and characteristics of particles in domestic and fetal pig lung tissue in the natural environment. Specimens from the lungs of domestic pigs (n = 10) and fetal pigs that already died in matrix during vaginal birth from the non-contaminated area (n = 10) were obtained from farmers' nearby sludge treatment plant. These specimens were compressed between two glass microscope slides, which were examined under polarized light microscopy. In addition, Agilent 8700 LDIR Chemical imaging system (LDIR) was used to determine the quantitative and qualitative characteristics of MPs. According to the polarized light microscope survey of domestic pig lungs, we observed an average of 12 particles/g, which was more than the 6 particles/g observed in fetal pig lungs, which ranged in size from 115.14 µm to 1370.43 µm. All the observed MP particles were fiber in shape. LDIR indicated an average of 180 particles/g of domestic pig lungs, ranging in size from 20.34 µm to 916.36 µm, which was twice as many MPs observed in fetal pig lungs. Furthermore, the compositions of MPs were different between them. LDIR indicated that polyamide (PA) was the most common polymer identified in domestic pig lungs (46.11%), while polycarbonate (PC) was the most common polymer in fetal pig lungs (32.99%). These findings confirmed the presence of MPs in the lung tissue of both domestic and fetal pigs in the natural environment, but the main characteristics differed. This fact indicated the increasing risk of MPs to human respiratory tract is increasing. Further research should be conducted to entirely estimate the specific exposure level on humans and offspring.

Preparation of amentoflavone-loaded DSPE-PEG2000 micelles with improved bioavailability and in vitro antitumor efficacy.

To overcome the poor aqueous solubility and enhance the anticancer effects of amentoflavone (AF), a nontoxic and biodegradable amphiphilic copolymer, poly(ethyleneglycol)-distearoylphosphatidylethanolamine (DSPE-PEG2000 ), was introduced to prepare AF micelles using the thin-film hydration method. Amentoflavone was successfully encapsulated into the core, achieving an encapsulation efficiency of 98.80 ± 0.24% and a drug loading efficiency of 2.96 ± 0.12%. The resulting micelles exhibited a spherical shape with a particle size of approximately 25.99 nm. The solubility of AF was significant improved by 412-fold, and cumulative drug release studies showed that AF release was much faster from the micelles compared with the free drug. The release of AF was sustained over time and followed a degradation-based kinetic model, similar to polymeric systems. After oral administration, the AF-loaded micelles demonstrated an enhanced oral bioavailability, which was 3.79 times higher than that of free AF. In vitro evaluations of the micelles' antitumor effects revealed a significantly greater efficacy compared with free AF. These findings highlight the tremendous potential of DSPE-PEG2000 micelles as a drug delivery carrier for improving the solubility and therapeutic efficacy of AF.

Broadening the Substrate Specificity of Cellobiose Phosphorylase from Clostridium thermocellum for Improved Transformation of Cellodextrin to Starch.

Cellobiose phosphorylase (CBP) catalyzes the reversible phosphorolysis of cellobiose into α-glucose 1-phosphate and glucose. A CBP with a broadened substrate specificity would be more desirable when utilized to convert cellulose into amylose (PNAS, 110: 7182-7187, 2013) and to construct yeast that can phosphorolytically use cellodextrin to produce ethanol. Based on the structure differences in the catalytic loops of CBP and cellodextrin phosphorylase from Clostridium thermocellum (named CtCBP and CtCDP, respectively), CtCBP was mutated to change its substrate specificity. A single-site mutant S497G was identified to exhibit a 5.7-fold higher catalytic efficiency with cellotriose as a substrate in the phosphorolytic reaction compared to the wild type, without any loss of catalytic efficiency on its natural substrate, cellobiose. When the S497G variant was used in the transformation of mixed cellodextrin (cellobiose + cellotriose) to amylose, the amylose yield was significantly increased compared to that of wild-type CtCBP. A structure change in the substrate-binding pocket of the S497G variant accounted for its capacity to accept longer cellodextrins than cellobiose. Taken together, the modified CtCBP, S497G was confirmed to acquire a promising feature favorable to those application scenarios involving cellodextrin's phosphorolysis.

High-efficiency cleaning technology and lifespan prediction for the ceramic membrane treating secondary treated effluent.

Chemical cleaning is one of the key technical means to control membrane fouling, restore membrane flux and ensure the stable operation of membrane systems. In the experiment, the six most representative chemical cleaning agents for ceramic membranes, such as sulfuric acid (H2SO4), sodium hydroxide (NaOH), sodium hypochlorite (NaClO), ethylenediaminetetraacetic acid disodium salt (EDTA-Na2), sodium dodecyl sulfate (SDS) and nonylphenol polyoxyethylene ether (OP-10), were used as research objects. The cleaning effect of the two-step combined cleaning of chemical cleaning agents on the fouled membrane was systematically investigated. Results showed that the order of the chemical cleaning agent had a significant effect on the cleaning effect. The best chemical cleaning program was determined to be NaClO first and then SDS: the fouled ceramic membrane was soaked in NaClO solution at 0.15% for 2.5 h and further soaked in SDS solution at five times its own critical micelle concentration for 2.5 h. The predicted long-term lifespan of the ceramic membranes was 4.91 years. Scanning electron microscopy-energy spectrum analysis showed that the surface roughness of the cleaned ceramic membrane was slightly higher than that of the new membrane. The contact angle was slightly lower than that of the new membrane.

The Class II KNOX family members KNAT3 and KNAT7 redundantly participate in Arabidopsis seed coat mucilage biosynthesis.

The production of Arabidopsis seed mucilage involves complex polysaccharide biosynthetic pathways and developmental processes in seed epidermal cells. Although the polysaccharide components of Arabidopsis seed mucilage have been identified, their regulatory mechanism requires further investigation. Here, we show that Class II KNOX gene family members KNAT3 and KNAT7 play an essential role in regulating mucilage production in the early developmental stages of Arabidopsis seeds. Double mutant knat3knat7 resulted in defective seed mucilage production and columellae formation, whereas knat3 showed a normal phenotype compared with wild type, and the mucilage thickness in knat7 was slightly disturbed. Rhamnogalacturonan I (RG-I) and its biosynthetic substrates galacturonic acid and rhamnose were reduced in both the adherent and soluble mucilage of knat3knat7. Comparative transcriptome analysis on whole seeds suggested that polysaccharide, glucosinolate and anthocyanin biosynthetic pathways were specifically repressed in knat3knat7. Transient co-expression of KNAT3 and KNAT7 with promoter regions of candidate genes in Arabidopsis protoplasts revealed that both KNAT3 and KNAT7 act as positive regulators of the RG-I biosynthetic gene MUCILAGE-MODIFIED 4 (MUM4, AT1G53500). Collectively, our results demonstrate that KNAT3 and KNAT7 are multifunctional transcription factors in secondary cell wall development and redundantly modulate mucilage biosynthesis in Arabidopsis seeds.

All-in-one theranostic nano-platform based on polymer nanoparticles for BRET/FRET-initiated bioluminescence imaging and synergistically anti-inflammatory therapy for ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), has evolved into a global burden given its high incidence. There is a clinical need to create better diagnostic and therapeutic approaches to UC. RESULTS: We fabricated P-selectin binding peptide-decorated poly lactic-co-glycolic acid (PBP-PLGA-NP) doped with two lipophilic dyes, DiL and DiD. Meanwhile, two low-toxic anti-inflammatory natural products (betulinic acid [BA] and resveratrol [Res]) were co-loaded in the PBP-PLGA-NP system. The BA/Res-loaded NPs had an average size of around 164.18 nm with a negative zeta potential (- 25.46 mV). Entrapment efficiencies of BA and Res were 74.54% and 52.33%, respectively, and presented a sustained drug release profile. Further, the resulting PBP-PLGA-NP could be internalized by RAW 264.7 cells and Colon-26 cells efficiently in vitro and preferentially localized to the inflamed colon. When intravenously injected with luminol, MPO-dependent bioluminescence imaging to visualize tissue inflammation was activated by the bioluminescence and fluorescence resonance energy transfer (BRET-FRET) effect. Importantly, injected NPs could remarkably alleviate UC symptoms yet maintain intestinal microbiota homeostasis without inducing organ injuries in the mice models of colitis. CONCLUSIONS: This theranostic nano-platform not only serves as a therapeutic system for UC but also as a non-invasive and highly-sensitive approach for accurately visualizing inflammation.

Design, Preparation, and Evaluation of Osthol Poly-Butyl-Cyanoacrylate Nanoparticles with Improved In Vitro Anticancer Activity in Neuroblastoma Treatment.

Osthol (osthole), known as a neuroprotective drug, has shown potent anticancer activity. However, the potential clinical application of osthol is limited due to its low water solubility and low bioavailability. Polybutyl cyanoacrylate (PBCA) has been widely used to improve the solubility of drugs with poor water solubility. In this study, an orthogonal experimental design (OED) was applied to design the preparation process of PBCA nanoparticles (NPs). Then, nanoparticles were prepared and evaluated in terms of physicochemical properties, in vitro release, and cellular uptake, etc. Further, the anti-cancer activity of osthol-PBCA NPs was demonstrated in SH-SY5Y cells. The pharmacokinetics and area under the curve (AUC) were investigated. The obtained osthol-NPs presented a spherical shape with a particle size of 110 ± 6.7 nm, a polydispersity index (PDI) of 0.126, and a zeta potential of −13 ± 0.32 mV. Compared with the free osthol, the drugs in osthol-NPs presented better stability and sustained release pattern activity. In vitro analysis using SH-SY5Y neuroblastoma cells showed that osthol-loaded nanoparticles displayed a significantly enhanced intracellular absorption process (three times) and cytotoxicity compared with free osthol (p < 0.05, increased 10−20%). The in vivo pharmacokinetic study revealed that the AUC of osthol-NPs was 3.3-fold higher than that of free osthol. In conclusion, osthol-PBCA NPs can enhance the bioactivity of osthol, being proposed as a novel, promising vehicle for drug delivery.

Studies of anticancer activity in vivo and in vitro behaviors of liposomes encapsulated iridium(III) complex.

Iridium(III) complexes have gained great attention in cancer treatment in recent years. In this paper, we designed and synthesized a new iridium(III) complex [Ir(piq)2(DQTT)](PF6) Ir1 (piq = 1-phenylisoquinoline, DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene). The Ir1-loaded PEGylated liposomes (Lipo-Ir1) were prepared using the ethanol injection method. The anticancer activity of the complex and Lipo-Ir1 against SGC-7901 (human gastric adenocarcinoma), A549 (human lung carcinoma), HeLa (human cervical carcinoma), HepG2 (human hepatocellular carcinoma), BEL-7402 (human hepatocellular carcinoma), and normal NIH3T3 (mouse embryonic fibroblasts) was tested by the MTT method. The complex Ir1 shows moderate or low cytotoxicity against the selected cancer cells, whereas the Lipo-Ir1 exhibits high anticancer activity toward the same cancer cells. The apoptosis induced by Lipo-Ir1 was assayed by flow cytometry and Lipo-Ir1 induced apoptosis through increasing intracellular reactive-oxygen species levels, decreasing mitochondrial membrane potential, further promoting cytochrome c release and causing the increase of level of intracellular Ca2+. Western blot was used to detect the changes in Bcl-2 family protein and PI3K/AKT pathway proteins. The cloning experiments demonstrated that the Lipo-Ir1 can effectively inhibit cell proliferation. In vivo experiments, Lipo-Ir1 inhibited tumor growth in xenograft nude mice, and the percentage of tumor growth inhibition in vivo was 75.70%. Overall, the liposomes Lipo-Ir1 exhibits higher anticancer activity than Ir1 under the same conditions. These results indicated that Lipo-Ir1 may be a valuable resource for cancer therapy.

Central neck lymph node metastasis in oral squamous cell carcinoma at the floor of mouth.

BACKGROUND: Our goal was to analyze the incidence of level VI metastasis in previously untreated oral squamous cell carcinoma (SCC) patients and their clinicopathological and prognostic characteristics. METHODS: Oral SCC patients with level VI metastasis were retrospectively enrolled, and their demographic and pathologic features as well as their survival data were descriptively analyzed. RESULTS: A total of 13 cases from 1875 patients were included, all patients had SCC at the floor of mouth (SCCFOM). Eight (61.5%) patients had a pT4 tumor, and all patients had a pathological N3 neck with multiple positive lymph nodes. Adverse pathologic features were present in 100% of the patients. The size of the metastatic foci in level VI ranged from 2.6 cm to 4.5 cm with a mean value of 3.2 cm, and 5 patients showed a soft tissue deposit with no lymph node component. Recurrence occurred in all patients, and 11 patients died of uncontrolled cancer within 5 years after surgery. CONCLUSION: Level VI metastasis in primary oral SCCFOM is rare, and its prognosis is poor.

Toolbox of Biodegradable Dendritic (Poly glycerol sulfate)-SS-poly(ester) Micelles for Cancer Treatment: Stability, Drug Release, and Tumor Targeting.

In this paper, we present well-defined dPGS-SS-PCL/PLGA/PLA micellar systems demonstrating excellent capabilities as a drug delivery platform in light of high stability and precise in vitro and in vivo drug release combined with active targetability to tumors. These six amphiphilic block copolymers were each targeted in two different molecular weights (8 or 16 kDa) and characterized using 1H NMR, gel permeation chromatography (GPC), and elemental analysis. The block copolymer micelles showed monodispersed size distributions of 81-187 nm, strong negative charges between -52 and -41 mV, and low critical micelle concentrations (CMCs) of up to 1.13-3.58 mg/L (134-527 nM). The serum stability was determined as 94% after 24 h. The drug-loading efficiency for Sunitinib ranges from 38 to 83% (8-17 wt %). The release was selectively triggered by glutathione (GSH) and lipase, reaching 85% after 5 days, while only 20% leaching was observed under physiological conditions. Both the in vitro and in vivo studies showed sustained release of Sunitinib over 1 week. CCK-8 assays on HeLa lines demonstrated the high cell compatibility (1 mg/mL, 94% cell viability, 48 h) and the high cancer cell toxicity of Sunitinib-loaded micelles (IC50 2.5 µg/mL). By in vivo fluorescence imaging studies on HT-29 tumor-bearing mice, the targetability of dPGS7.8-SS-PCL7.8 enabled substantial accumulation in tumor tissue compared to nonsulfated dPG3.9-SS-PCL7.8. As a proof of concept, Sunitinib-loaded dPGS-SS-poly(ester) micelles improved the antitumor efficacy of the chemotherapeutic. A tenfold lower dosage of loaded Sunitinib led to an even higher tumor growth inhibition compared to the free drug, as demonstrated in a HeLa human cervical tumor-bearing mice model. No toxicity for the organism was observed, confirming the good biocompatibility of the system.

Liposome as drug delivery system enhance anticancer activity of iridium (III) complex.

Herein an Ir(III) complex [Ir(Hppy)2(HMNPIP)](PF6) (Ir1, Hppy = 2-phenylpyridine, HMNPIP = 2-(1H-imidazo[4,5-f][1, 10]phenanthroline-3-yl)-6-methoxy-4-nitrophenol) was prepared and characterized. Due to the low anticancer activity of Ir1 when administered free drug, we prepared a liposome Ir1Lipo encapsulated form of Ir1 to improve the antitumor effect, furthermore, we explored the antitumor mechanism of both forms in vitro experiments on HepG2 cells. We investigated the inhibitory efficiency of Ir1 and Ir1Lipo on cell viability and proliferation using MTT (MTT = 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide) and colony-forming assay. Intracellular accumulation of reactive oxygen species (ROS) was examined using a fluorescence microscope (High Content Screening System, ImageXpress Micro XLS System, Molecular Devices LLC, Sunnyvale, CA), programmed cell death cells stained with acridine orange/ethidium bromide (AO/EB) using flow cytometry detection and western blot have been performed. An in vivo study where HepG2 cells were transplanted into nude nice as xenografts. Tumour volume and body weight were monitored during the 10 days of administration. After encapsulation in liposomes Ir1Lipo displayed high potency against a variety of tumour cells in vitro, especially against HepG2 (IC50 = 4.6 ± 0.5 µM). Mechanism studies indicated that Ir1Lipo initiated apoptosis by generating intracellular ROS that regulate lysosomal-mitochondrial dysfunction, followed by microtubule disruption that subsequently leads to a G0/G1 phase of cell cycle arrest. Additionally, Ir1Lipo significantly curbed tumour growth in nude mice. The tumour inhibitory rate was 51.2% (5.6 mg/kg). Therefore, liposome as a drug delivery system greatly enhances anticancer activity of Ir1 by a factor of relatively minor side effects.

Complete mitochondrial genome of Iniistius trivittatus and unique variation in two observed inserts between rRNA and tRNA genes in wrasses.

BACKGROUND: The family Labridae made up of 519 species in the world. The functional evolution of the feeding-related jaws leaded to differentiation of species, and the pharyngeal jaw apparatus evolved independently, but evolutionary mechanism still remain unaddressed in wrasses. Mitogenomes data can be used to infer genetic diversification and investigate evolutionary history of wrasses, whereas only eight complete mitogenomes in this family have been sequenced to date. Here, we sequenced the complete mitogenomes of Iniistius trivittatus to investigate genetic differentiation among wrasse species. RESULTS: We sequenced the complete mitogenomes of I. trivittatus using a novel PCR strategy. The I. trivittatus mitogenomes is 16,820 bp in length and includes 13 protein -coding genes, 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a control region. Compared to eight known mitochondrial genome, 2 additional noncoding regions (lengths of 121 and 107 bp), or so-called inserts, are found in the intergenic regions 12S rRNA - tRNAVal - 16S rRNA. The presumed origin of the two rare inserts is from tRNA- related retrotransposons. Compared with cytochrome b gene, the two insert sequences are highly conserved at the intraspecies level, but they showed significant variation and low similarity (< 70%) at the interspecies level. The insert events were only observed in I. trivittatus by checking the phylogenetic trees based on the complete mitogenomes of Labrida species. This finding provides evidence that in the mitogenomes, retrotransposon inserts result in intraspecific homoplasmy and interspecific heteroplasmy by natural selection and adaptation to various environments. CONCLUSIONS: This study found additional mitogenome inserts limited in wrasse species. The rRNA genes with inserts might have experienced a selective pressure for adaptation to feeding modes. Such knowledge can enable a better understanding of molecular mechanism underlying morphological evolution in wrasses.

Label-free graphene oxide-based SPR genosensor for the quantification of microRNA21.

This work is focused on the development of a genosensor for microRNA-21 quantification using surface plasmon resonance (SPR) to transduce the hybridization event. The biosensing platform was built by self-assembling two bilayers of poly(diallyldimethylammonium chloride) (PDDA) and graphene oxide (GO) at a gold surface modified with 3-mercaptopropane sulfonate (MPS), followed by the covalent attachment of the DNA probe. GO was used in two directions, to allow the anchoring of the probe DNA and to increase the sensitivity of the biosensing event due to its field enhancer effect. The new bioanalytical platform represents an interesting alternative for the label-free biosensing of microRNA-21, with a linear range between 1.0 fM and 10 nM, a sensitivity of 5.1 ± 0.1 moM-1 and a detection limit of 0.3fM. The proposed sensing strategy was successfully used for the quantification of microRNA-21 in enriched urine samples. Graphical abstract.

Development and optimization of levodopa and benzylhydrazine orally disintegrating tablets by direct compression and response surface methodology.

The number of Parkinson's disease (PD) patients with the advanced phase and motor fluctuations is increasing. The objective of this study is developing levodopa/benzylhydrazine orally disintegrating tablets (L/B ODTs), which would provide greater convenience and ease of use than conventional tablets for these patients. In the present study, the L/B ODTs were developed successfully with an optimized formulation using response surface methodology (RSM). The direct compression technology was employed for the preparation of L/B ODTs. Considerably shorter disintegration time and faster dissolution profile were obtained under the optimum formulation with microcrystalline cellulose 25.7%, cross-polyvinylpyrrolidone 6.22% and Sodium carboxymethyl starch 5.36%. The content uniformity (%) of levodopa and benzylhydrazine was 50 ± 1.4% and 14.25 ± 0.6%, respectively. Thickness, friability, hardness and wetting time were 2.8 ± 0.05 mm, 0.46 ± 0.21%, 5.42 ± 1.1 kp and 31.2 ± 2.1 s, respectively, and all of data well comply with the General Principles of the Chinese Pharmacopeia. Mannitol of 22% in formulation could bring a pleasant taste: sweet, cool and refreshing. Almost all the volunteers felt that the ODTs had good taste, no roughness, and no gritty feeling, indicating that the ODTs prepared had good palatability, so patients will have good compliance when taking medicine.

Psychological problems and quality of life of patients with oral mucosal diseases: a preliminary study in Chinese population.

BACKGROUND: Psychological problems might play important roles in oral mucosal diseases such as recurrent aphthous ulcers (RAU), oral lichen planus (OLP), burning mouth syndrome (BMS), but the relevance to patients' quality of life remained controversial. The aim of this study was to investigate the psychological problems and oral health-related quality of life in patients with RAU, OLP, and BMS in China, to assess the relationship between psychological problems and quality of life. METHOD: Thirty-nine RAU patients, 45 OLP patients, 15 BMS patients and 45 healthy controls were enrolled in the study. Hospital Anxiety and Depression Scale (HADS) were chosen to analyze the patients' psychological problems. Oral Health Impact Profile (OHIP-14) was used to measure the OHRQoL. The scores of HADS and OHIP-14 were used to analyze the relationship between psychological problems and the quality of life of oral mucosa patients. RESULTS: Each of OHIP-14 scores and HADS scores in RAU, OLP, BMS was higher than the control group, and there was significant difference in the patients groups with the control cases(P < 0.05). OHIP-14 score of RAU was the highest in three patient groups. Its OHRQoL was lowest in the three groups, which had statistical significance (P < 0.05). Positive correlations existed between the psychological problems and the quality of life of the three patient groups (rs > 0, P < 0.05), except for the depression of the BMS group (rs = 0.168, P = 0.395). CONCLUSION: Patients with oral mucosal diseases such as RAU, OLP, and BMS had higher levels of anxiety, depression, and lower quality of life. The patient's psychological problems were related to their quality of life, suggesting that the psychological state of patients with oral mucosal disease need more attention.