Novel TFG mutation causes autosomal-dominant spastic paraplegia and defects in autophagy.

BACKGROUND: Mutations in the tropomyosin receptor kinase fused (TFG) gene are associated with various neurological disorders, including autosomal recessive hereditary spastic paraplegia (HSP), autosomal dominant hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) and autosomal dominant type of Charcot-Marie-Tooth disease type 2. METHODS: Whole genome sequencing and whole-exome sequencing were used, followed by Sanger sequencing for validation. Haplotype analysis was performed to confirm the inheritance mode of the novel TFG mutation in a large Chinese family with HSP. Additionally, another family diagnosed with HMSN-P and carrying the reported TFG mutation was studied. Clinical data and muscle pathology comparisons were drawn between patients with HSP and patients with HMSN-P. Furthermore, functional studies using skin fibroblasts derived from patients with HSP and patients with HMSN-P were conducted to investigate the pathomechanisms of TFG mutations. RESULTS: A novel heterozygous TFG variant (NM_006070.6: c.125G>A (p.R42Q)) was identified and caused pure HSP. We further confirmed that the well-documented recessively inherited spastic paraplegia, caused by homozygous TFG mutations, exists in a dominantly inherited form. Although the clinical features and muscle pathology between patients with HSP and patients with HMSN-P were distinct, skin fibroblasts derived from both patient groups exhibited reduced levels of autophagy-related proteins and the presence of TFG-positive puncta. CONCLUSIONS: Our findings suggest that autophagy impairment may serve as a common pathomechanism among different clinical phenotypes caused by TFG mutations. Consequently, targeting autophagy may facilitate the development of a uniform treatment for TFG-related neurological disorders.

Approaches to developing fast release pellets via wet extrusion-spheronization.

Microcrystalline cellulose (MCC) is widely regarded as the excellent choice to manufacture pellets via wet extrusion-spheronisation (ES) process due to its excellent water uptake capability, water holding capacity, desirable rheological properties, cohesiveness and plasticity etc. Nevertheless, in spite of all these advantages, limitations associated with the application of MCC also have been reported. The most prevailing limitation is prolonged or incomplete drug release profile due to the lack of disintegration as pellet contracts significantly during the drying process, especially when in combination with poorly soluble drug at a high level. This characteristic limits the application of MCC in immediate release formulations. Over the years, many approaches have been tried to overcome this disadvantage, such as modifying MCC, incorporation of superdisintegrant, increasing the porosity of pellet, partial or complete substitution for MCC, enhancing the solubility of poorly soluble drug (e.g. solid dispersion, self-emulsifying drug-delivery system), etc. In this review, we will provide an updated and integrated discussion of current approaches to prepare fast release pellets via wet ES.

A Super-Antifouling Electrochemical Biosensor for Protein Detection in Complex Biofluids Based on PEGylated Multifunctional Peptide.

Overcoming the influence of interfering substances in the environment and achieving superior sensing performance are significant challenges in biomarker detection within complex matrices. Herein, an integrated electrochemical sensing platform for sensitive detection of biomarkers in complex biofluids was developed based on a newly designed PEGylated multifunctional peptide (PEG-MPEP). The designed PEG-MPEP contains a poly(serine) sequence (-ssssss-) as the antifouling part and recognition peptide sequence (-avwgrwh) specific for the target human immunoglobulin G (IgG). To improve the peptide stability to protease hydrolysis, d-amino acids were adopted to synthesize the whole peptide. Additionally, the PEGylation can further enhance the stability of the peptide, and the PEG itself was also antifouling, ensuring superstrong antifouling capability of the PEG-MPEP. The designed PEG-MPEP-based biosensor possessed a high sensitivity for the detection of IgG in the range of 1.0 pg mL-1 to 1.0 µg mL-1, with a low limit of detection (0.41 pg mL-1), and it was capable of assaying targets accurately in real serum samples. Compared with conventional peptide-modified biosensors, the PEG-MPEP-modified biosensor exhibited superior antifouling and antihydrolysis properties in complex biofluid, showcasing promising potential for practical assay applications.

Fully bio-based intumescent flame retardant hybrid: A green strategy towards reducing fire hazard and improving degradation of polylactic acid.

Polylactic acid (PLA) is a promising renewable polymer material with excellent biodegradability and good mechanical properties. However, the easy flammability and slow natural degradation limited its further applications, especially in high-security fields. In this work, a fully bio-based intumescent flame-retardant system was designed to reduce the fire hazard of PLA. Firstly, arginine (Arg) and phytic acid (PA) were combined through electrostatic ionic interaction, followed by the introduction of starch as a carbon source, namely APS. The UL-94 grade of PLA/APS composites reached V-0 grade by adding 3 wt% of APS and exhibited excellent anti-dripping performance. With APS addition increasing to 7 wt%, LOI value increased to 26 % and total heat release decreased from 58.4 (neat PLA) to 51.1 MJ/m2. Moreover, the addition of APS increased its crystallinity up to 83.5 % and maintained the mechanical strength of pristine PLA. Noteworthy, APS accelerated the degradation rate of PLA under submerged conditions. Compared with pristine PLA, PLA/APS showed more apparent destructive network morphology and higher mass and Mn loss, suggesting effective degradation promotion. This work provides a full biomass modification strategy to construct renewable plastic with both good flame retardancy and high degradation efficiency.

Janus Membrane-Based Wearable pH Sensor with Sweat Absorption, Gas Permeability, and Self-Adhesiveness.

Wearable biomedical sensors have enabled noninvasive and continuous physiological monitoring for daily health management and early detection of chronic diseases. Among biomedical sensors, wearable pH sensors attracted significant interest, as pH influences most biological reactions. However, conformable pH sensors that have sweat absorption ability, are self-adhesive to the skin, and are gas permeable remain largely unexplored. In this study, we present a pioneering approach to this problem by developing a Janus membrane-based pH sensor with self-adhesiveness on the skin. The sensor is composed of a hydrophobic polyurethane-polydimethylsiloxane porous hundreds nanometer-thick substrate and a hydrophilic poly(vinyl alcohol)-poly(acrylic acid) porous nanofiber layer. This Janus membrane exhibits a thickness of around 10 µm, providing a conformable adhesion to the skin. The simultaneous realization of solution absorption, gas permeability, and self-adhesiveness makes it suitable for long-term continuous monitoring without compromising the comfort of the wearer. The pH sensor was tested successfully for continuous monitoring for 7.5 h, demonstrating its potential for stable analysis of skin health conditions. The Janus membrane-based pH sensor holds significant promise for comprehensive skin health monitoring and wearable biomedical applications.

Graphene-coated copper-doped ZnO quantum dots for sensitive photoelectrochemical bioanalysis of thrombin triggered by DNA nanoflowers.

This work reports a photoelectrochemical (PEC) biosensing platform for the sensitive and specific screening of thrombin by using graphene oxide-coated copper-doped zinc oxide quantum dots (Cu0.3Zn0.7O-GO QDs) as the photoactive materials and glucose oxidase-encapsulated DNA nanoflowers (GOx-DFs) for signal amplification. Interestingly, the coated graphene oxide nanosheets on the surface of the Cu0.3Zn0.7O QDs could cause the charge to transfer rapidly and ameliorate the photocorrosion. The doped copper into the quantum dots could enhance the absorption of visible light by tuning the band gap of ZnO QDs, therefore increasing the photocurrent under visible irradiation. Upon addition of target thrombin, a sandwiched reaction was carried out between thrombin aptamer and GOx-DFs, accompanying the formation of nanocomposites with the magnetic microparticles (MMPs)/thrombin/GOx-DFs. Followed by magnetic separation, the carried GOx oxidized glucose to H2O2, thus resulting in the increasing photocurrent of the Cu0.3Zn0.7O-GO QD-modified electrode. Under optimum conditions, the developed PEC biosensing platform exhibited good analytical performance with a linear range of 50-10 000 fM thrombin and a limit of detection of 29 fM. Impressively, our strategy offers a new horizon in developing bridge-connected graphene-coated nanomaterials and novel signal amplification strategy for the development of PEC biosensors.

Impacts of surface wettability and roughness of styrene-acrylic resin films on adhesion behavior of microalgae Chlorella sp.

Biofilm attached cultivation is a promising method for efficient production of microalgae. Determining the surface property index to select an appropriate substrate benefiting the algae adhesion and biofilm formation is very important for the cultivation method. This work focused on elucidating and quantifying the influence of surface wettability and roughness of substrate on Chlorella vulgaris adhesion. Firstly, surface modified styrene-acrylic (SA) resin films by adding different dosage of perfluoroalkyl ethyl acrylate (FM) were prepared. Property characterization shows that the surface contact angle in water, formamide and diiodomethane of FM modified SA films is significantly associated with the FM dosage, while the other surface properties including zeta potential, surface potential and surface roughness have insignificant difference. The calculated surface free energy parameters show that the SA films belong to the non-polar substrata. A well quantitative correlation that the adhesion capacity of C. vulgaris linearly declines with the increase of water contact angle was obtained. And a near linear relationship between the adhesion capacity and the surface free energy (γ), or the cohesion free energy (ΔGcoh) was also observed. Secondly, the surface roughness solely changed SA films were prepared by replicating the morphology of stainless steel sieves through the PDMS template method. The patterned SA films have alternately arranged rectangular "valleys" and "ridges". A well linear correlation between the microalgae adhesion capacity and the surface roughness was also obtained.

Acquired dermal melanocytosis: a case with conjunctival and gingival pigmentation.

A 28-year-old Japanese woman was referred to us because of widespread bilateral blue-gray and brown pigmentation on her face. Pigmentation was apparant on both sclerae, the alae of the nose, the lower lip and the gingiva; and it was also evident on her extremities. A biopsy specimen revealed melanin-containing cells and numerous mononulear cells in the upper dermis, particularly, near the small vessels. The melanin-containing cells immunoreacted with S100-specific antibodies but did not react with CD68-specific antibodies, these observations indicated that they were melanocytes. A diagnosis was made of acquired dermal melanocytosis (ADM), even though ADM is very rarely associated with conjunctival and mucosal involvement. Dermal melanocytes and large numbers of mononuclear cells adjacent to small vessels in the upper dermis have not previously been reported in ADM. Such melanocytes might play an important role in protecting blood cells from ultraviolet light. The presence of mononuclear cells close to melanocytes suggests that an inflammatory reaction might have initiated the activation of these dermal melanocytes.

Study on the distribution of active centers in novel low Ti-loading MgCl2-supported Ziegler-Natta catalyst.

Novel MgCl2-supported Ziegler-Natta (Z-N) catalysts prepared using a new one-pot ball milling method can effectively control the amounts of Ti-loading in the catalysts. Complex GPC data on polypropylene synthesized by these novel catalysts were analyzed using the method of fitting the molecular weight distribution (MWD) curves with a multiple Flory-Schulz function. It was found that multiple active centers exist in these novel catalysts. Detailed study of the effects of the Ti-loadings in the catalysts on the distribution of the active centers showed that the Ti-loadings in the novel MgCl2-supported Z-N catalysts might affect the proportion of each type of active centers; and might be the main factor responsible for the effect of the Ti-loadings on the microstructure, the molecular weight and molecular weight distribution width of the resultant polymer, the catalytic activity and polymerization kinetics.