Trueperella pyogenes is an important opportunistic pathogenic bacterium widely distributed in the environment. Pyolysin (PLO) is a primary virulence factor of T. pyogenes and capable of lysing many different cells. PLO is a member of the cholesterol-dependent cytolysin (CDC) family of which the primary structure only presents a low level of homology with other members from 31% to 45%. By deeply studying PLO, we can understand the overall pathogenic mechanism of CDC family proteins. This study established a mouse muscle tissue model infected with recombinant PLO (rPLO) and its single-point mutations, rPLO N139K and rPLO F240A, and explored its mechanism of causing inflammatory damage. The inflammatory injury abilities of rPLO N139K and rPLO F240A are significantly reduced compared to rPLO. This study elaborated on the inflammatory mechanism of PLO by examining its unit point mutations in detail. Our data also provide a theoretical basis and practical significance for future research on toxins and bacteria.

Surface functionalization of mesoporous silica nanoparticles (MSNs) has been proposed as an efficient strategy for enhancing the biocompatibility and efficiency of an MSN-based carrier platform. Herein, natural polyelectrolyte multilayers composed of poly-l-ornithine (PLO) and carboxymethyl lentinan (LC) were coated on the surface of MSNs through a layer-by-layer (LbL) self-assembly technique, and were characterized by ζ-potential, FTIR, 13C NMR, SEM, TEM, XRD, and TG. The prepared carrier presented alternating positive and negative potentials when coated with the polyelectrolytes, and the surface of MSN-PLO/LC was rougher compared to the naked MSNs. The biocompatibility tests, including cytocompatibility, hemocompatibility, and histocompatibility, showed that MSNs biocompatibility could be improved by modifying LC. A high loading and sustained release drug delivery system was constructed after loading doxorubicin (DOX) into the prepared MSN-PLO/LC, which exhibited significant anti-proliferative efficiency in human cervical cancer cell lines (Hela). Therefore, the PLO/LC LbL NPs (layer-by-layer self-assembled nanoparticles coated with PLO/LC layers) based on MSNs, which is easily prepared by electrostatic interactions, can be considered a promising drug chemotherapeutic platform and delivery technique for future human cervical cancer therapy.

UNASSIGNED: Pregnancy and lactation-associated osteoporosis (PLO) is very rare, which typically occurs during the third trimester or during lactation. Many cases of PLO are associated with vertebral compression fractures or hip fractures, while distal radius fractures in patients with PLO are rarely reported.
UNASSIGNED: A 36-year-old patient presented with Barton fracture at 37 weeks of gestation. Temporary closed reduction and plaster external fixation were performed in emergency room. At 38 weeks of gestation, she gave birth to a healthy boy and began breastfeeding after delivery. Three days after delivery, the patient was admitted to the orthopedic ward for surgery and was diagnosed as PLO. The patient underwent open reduction and internal fixation and treated with weaning and supplementation of calcium carbonate and vitamin D. During the 1-year follow-up period, the results of laboratory tests and bone mineral density gradually returned to normal.
UNASSIGNED: Clinicians should be alert to the possibility of PLO to avoid missed diagnosis. Accurate diagnosis and individualized treatment are of great significance for relieving pain and functional recovery of patients.

BACKGROUND: Lipids perform multiple functions in the cell, and lipid-protein interactions play a key role in metabolism. Although various techniques have been developed to study lipid-protein interactions, the interacting protein partners that bind to most lipids remain unknown. The protein lipid overlay (PLO) assay has revealed numerous lipid-protein interactions, but its application suffers from unresolved technical issues.
RESULTS: Herein, we found that blocking proteins may interfere with interactions between lipids and their binding proteins if a separate blocking step is carried out before the incubation step in the PLO assay. To overcome this, we modified the PLO assay by combining an incubation step alongside the blocking step. Verification experiments included phosphatidylinositol-3-phosphate (PI3P) and its commercially available interacting protein G302, C18:1, C18:2, C18:3 and the Arabidopsis plasma membrane H+-ATPase (PM H+-ATPase) AHA2 C-terminus, phosphatidylglycerol (PG) and AtROP6, and phosphatidylserine (PS) and the AHA2 C-terminus. The lipid-protein binding signal in the classical PLO (CPLO) assay was weak and not reproducible, but the modified PLO (MPLO) assay displayed significantly improved sensitivity and reproducibility.
CONCLUSIONS: This work identified a limitation of the CPLO assay, and both sensitivity and reproducibility were improved in the modified assay, which could prove to be more effective for investigating lipid-protein interactions.

Increasing demands for individualized drug treatment has led to an increase in the practice of compounded medications. In this study, we determined the impact of the chemical and physical stability of ketoprofen (10%w/w) cream on its topical/transdermal delivery over a 6-month period. The shelf life of ketoprofen at 25 °C in the pharmaceutical bases LipoDerm and LipoBase (109.94 and 85.9 days) was significantly longer than that in Pluronic Lecithin Organogel (PLO; 44.81 days), justifying extending its beyond use date (BUD) from 30 (USP37/NF32) to at least 60 days in LipoDerm and LipoBase. All the creams evaluated exhibited shear-thinning flow behavior with moderate thixotropy, while the flow properties for LipoBase and PLO creams were altered at storage times greater than 90 days. The percentage of ketoprofen permeated through porcine ear skin was 13.7, 19.1 and 12.7% of the dose from LipoDerm, LipoBase and PLO, respectively and decreased 2- to 3-fold after 28 days of storage. Flux ranging from 85.3 to 446.7 µg/cm(2)/h and topical delivery, on the other hand, were not influenced by storage duration past 28 days. In conclusion, this study justifies extending the BUD of ketoprofen in LipoDerm and LipoBase to 60 days if used for topical delivery only.

In the last decade, we have experienced an increasing interest and an improved understanding of the application of nanotechnology to the nervous system. The aim of such studies is that of developing future strategies for tissue repair to promote functional recovery after brain damage. In this framework, carbon nanotube based technologies are emerging as particularly innovative tools due to the outstanding physical properties of these nanomaterials together with their recently documented ability to interface neuronal circuits, synapses and membranes. This review will discuss the state of the art in carbon nanotube technology applied to the development of devices able to drive nerve tissue repair; we will highlight the most exciting findings addressing the impact of carbon nanotubes in nerve tissue engineering, focusing in particular on neuronal differentiation, growth and network reconstruction.