Environmental colloid behaviors of humic acid - Cadmium nanoparticles in aquatic environments.

Humic acid (HA), a principal constituent of natural organic matter (NOM), manifests ubiquitously across diverse ecosystems and can significantly influence the environmental behaviors of Cd(II) in aquatic systems. Previous studies on NOM-Cd(II) interactions have primarily focused on the immobilization of Cd(II) solids, but little is known about the colloidal stability of organically complexed Cd(II) particles in the environment. In this study, we investigated the formation of HA-Cd(II) colloids and quantified their aggregation, stability, and transport behaviors in a saturated porous media representative of typical subsurface conditions. Results from batch experiments indicated that the relative quantity of HA-Cd(II) colloids increased with increasing C/Cd molar ratio and that the carboxyl functional groups of HA dominated the stability of HA-Cd(II) colloids. The results of correlation analysis between particle size, critical aggregation concentration (CCC), and zeta potential indicated that both Derjaguin-Landau-Verwey-Overbeek (DLVO) and non-DLVO interactions contributed to the enhanced colloidal stability of HA-Cd(II) colloids. Column results further confirmed that the stable HA-Cd(II) colloid can transport fast in a saturated media composed of clean sand. Together, this study provides new knowledge of the colloidal behaviors of NOM-Cd(II) nanoparticles, which is important for better understanding the ultimate cycling of Cd(II) in aquatic systems.

Rational development of functional hydrophilic polymer to characterize site-specific glycan differences between bovine milk and colostrum.

As vastly modified on secreted proteins, N-glycosylation is found on milk proteins and undergo dynamic changes during lactation, characterizing milk protein glycosylation would benefit the elucidation of glycosylation pattern differences between samples. However, their low abundance required specific enrichment. Herein, through rational design and controllable synthesis, we developed a novel multi-functional polymer for the isolation of protein glycosylation. It efficiently separated glycopeptides from complex background inferences with mutual efforts of hydrophilic interaction chromatography (HILIC), metal ion affinity and ion exchange. By fine-tuning Ca2+ as regulators of aldehyde hyaluronic acid (HA) conformation, the grafting density of HA was remarkably improved. Moreover, grafting Ti4+ further enhanced the enrichment performance. Application of this material to characterize bovine milk and colostrum proteins yields 479 and 611 intact glycopeptides, respectively. Comparative analysis unraveled the distinct glycosylation pattern as well the different distribution of glycoprotein abundances between the two samples, offering insights for functional food development.

Mechanism study of BMSC-exosomes combined with hyaluronic acid gel in the treatment of posttraumatic osteoarthritis.

Objective: To explore the mechanism and efficacy of gel in the treatment of posttraumatic osteoarthritis (PTOA), combined with hyaluronic acid (HA) and bone marrow mesenchymal stem cell exosomes (BMSC-EXOs), and to explain its role in alleviating oxidative stress damage induced by mitochondrial reactive oxygen species (ROS). Methods: How is the therapeutic potential of toa influenced by bone marrow mesenchymal stem cells-EXO to be evaluated both in vitro and in vivo. In vitro, BMSC-EXOs were extracted and characterized from rat specimens and labeled with Dil. Rat primary chondrocytes were then isolated to create a cellular PTOA model. BMSC-EXOs + HA group, BMSC-EXOs + HA + 740Y-P group, model group, BMSC-EXOs group, HA group, and control group were included in the cell group, and the function of cartilage matrix and the level of oxidative stress could be evaluated. Cartilage matrix integrity and oxidative stress can be assessed by grouping rats. At the same time, a rat model of ptosis can be established by excision of the anterior cruciate ligament, and joint rehabilitation, with pro-inflammatory and Enzyme-linked immunosorbent assay (ELISA) can be used to determine anti-inflammatory markers. Result: sThe combined use of BMSC-EXOs and HA gel was found to significantly reduce oxidative stress in chondrocytes and PTOA rat models, improving cartilage mechanical properties more effectively than BMSC-EXOs alone. Conclusion: BMSC-EXOs combined with HA gel offer a promising treatment for PTOA by modulating damage caused by mitochondrial ROS-induced oxidative stress.

Dopamine-modified hyaluronic acid (DA-HA) as a novel dopamine-mimetics with minimal autoxidation and cytotoxicity.

Dopamine-modified hyaluronic acid (DA-HA) has been initially developed as an efficient coating and adhesion material for industrial uses. However, the biological activity and safety of DA-HA in the brain have not been explored yet. Here, we report a series of evidence that DA-HA exhibits similar functionality as dopamine (DA), but with much lower toxicity arising from autoxidation. DA-HA shows very little autoxidation even after 48-h incubation. This is profoundly different from DA and its derivatives including l-DOPA, which all induce severe neuronal death after pre-autoxidation, indicating that autoxidation is the cause of neuronal death. Furthermore, in vivo injection of DA-HA induces significantly lower toxicity compared to 6-OHDA, a well-known oxidized and toxic form of DA, and alleviates the apomorphine-induced rotational behavior in the 6-OHDA animal model of Parkinson's disease. Our study proposes that DA-HA with DA-like functionalities and minimal toxicity has a great potential to treat DA-related disease.

Super-Selective Intra-arterial Thrombolytic Therapy for Peripheral Facial Paralysis After Postauricular Hyaluronic Acid Injection for the Esthetic Correction of Lying Ears.

BACKGROUND: Hyaluronic acid (HA) injection in the auricular base is one of the most popular and non-surgical cosmetic procedures for correcting lying ears and optimizing the facial profile because of its minimal invasiveness, immediate effect and safety (Li et al. in Aesthet Surg J 44: 746-75, 2024). But we have recently discovered that this treatment may lead to a new and rare complication called peripheral facial paralysis that has never been reported before. Until now, the etiology, clinical traits, treatment strategies, outcomes and possible reversibility have not been characterized. METHODS: In the present study, we enrolled 4 patients with peripheral facial paralysis after subcutaneous postauricular HA filler injection. Preoperative digital subtraction angiography revealed a vascular embolism. Then, the patients underwent super-selective facial arterial thrombolytic therapy via hyaluronidase and papaverine injections. Simultaneously, general symptomatic treatment and nutritional therapy were performed. RESULTS: The patients were relieved of their clinical symptoms and the significant improvement was observed in terms of motor function in her left facial areas after treatment. The auricular skin necrosis of all patients was restored to near normal appearance. CONCLUSION: Our results indicate that super-selective facial arterial thrombolytic therapy is feasible for patients with peripheral facial paralysis induced by HA embolism. It was also beneficial in the recovery from skin necrosis. The therapy was shown to be worthy of clinical application. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hsa_circ_0007765 Promotes Platelet-Derived Growth Factor-BB-Induced Proliferation and Migration of Human Aortic Vascular Smooth Muscle Cells in Atherosclerosis.

Human aortic vascular smooth muscle cells (HA-VSMCs) play vital roles in the pathogenesis of vascular diseases, including Atherosclerosis (AS). Circular RNAs (circRNAs) have been reported to regulate the biological functions of HA-VSMCs. Therefore, this study aimed to explore the role and mechanism of hsa_circRNA_102353 (circ_0007765) in platelet-derived growth factor-BB (PDGF-BB)-induced HA-VSMCs. Circ_0007765, microRNA-654-3p (miR-654-3p), and Fibroblast Growth Factor Receptor Substrate 2 (FRS2) expression were measured using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative ability, invasion, and migration were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), Transwell, and wound healing assays. CyclinD1, MMP2, and FRS2 protein levels were assessed using a Western blot assay. Binding between miR-654-3p and circ_0007765 or FRS2 was predicted by Circinteractome or TargetScan, and verified using dual-luciferase reporter and RNA pull-down assays. PDGF-BB induced HA-VSMC proliferation, invasion, and migration. Circ_0007765 and FRS2 expression levels were increased in PDGF-BB-treated HA-VSMCs, and the miR-654-3p level was reduced. Moreover, circ_0007765 absence hindered PDGF-BB-induced HA-VSMC proliferation, invasion, and migration in vitro. At the molecular level, circ_0007765 increased FRS2 expression by acting as a sponge for miR-654-3p. Our findings revealed that circ_0007765 boosted PDGF-BB-induced HA-VSMC proliferation and migration through elevating FRS2 expression via adsorbing miR-654-3p, providing a feasible therapeutic strategy for AS.

Collagen-hydroxyapatite based scaffolds for bone trauma and regeneration: recent trends and future perspectives.

Regenerative therapy, a key area of tissue engineering, holds promise for restoring damaged organs, especially in bone regeneration. Bone healing is natural to the body but becomes complex under stress and disease. Large bone deformities pose significant challenges in tissue engineering. Among various methods, scaffolds are attractive as they provide structural support and essential nutrients for cell adhesion and growth. Collagen and hydroxyapatite (HA) are widely used due to their biocompatibility and biodegradability. Collagen and nano-scale HA enhance cell adhesion and development. Thus, nano HA/collagen scaffolds offer potential solutions for bone regeneration. This review focuses on the use and production of nano-sized HA/collagen composites in bone regeneration.

[Box: see text].

The differential illusion memory for high-associated abstract concepts (DIM-HA) effect.

A vast body of evidence has shown that concrete concepts are processed faster and more accurately than abstract concepts in a variety of cognitive tasks. This phenomenon is widely known as the concreteness effect, and explanations for its occurrence seem to reflect differences in processing and organization for both types of representations. While there is considerable evidence to support this concreteness effect, the nature of these differences is still controversial. In developing an explanation, we have proposed a relatively different approach from a false memory perspective using the Deese-Roediger-McDermott paradigm. To explore the implications of the association in creating false memories, we explore behavioral and electrophysiologically the false memory effect, where targets were manipulated according to their association strength and their concreteness. Results showed that false recognition rates differed significantly between concrete and abstract critical words when they were associated strongly with their respective lists, which led to a higher proportion of abstract false alarms both in behavioral and electrophysiological experiments. The principal outcome, which was called the DIM-HA effect, was discussed in terms of theories of associative activation and qualitatively different representation.

Sensitization of hepatocellular carcinoma cells to HDACi is regulated through hsa-miR-342-5p/CFL1.

BACKGROUND: Increased prevalence of hepatocellular carcinoma (HCC) remains a global health challenge. HCC chemoresistance is a clinical obstacle for its management. Aberrant miRNA expression is a hallmark for both cancer progression and drug resistance. However, it is unclear which miRNAs are involved in HCC chemoresistance. METHODS: MicroRNA microarray analysis revealed a differential expression profile of microRNAs between the hepatocellular carcinoma HA22T cell line and the HDACi-R cell line, which was validated by quantitative real-time PCR (qRT-PCR). To determine the biological function of miR-342-5p and the mechanism of the microRNA-342-5p/CFL1 axis in hepatocellular carcinoma HDACi resistance, loss- and gain-of-function studies were conducted in vitro. RESULTS: Here we demonstrated the molecular mechanism of histone deacetylase inhibitor (HDACi) resistance in HCC. Differential miRNA expression analysis showed significant down regulation of miR-342-5p in HDACi-R cells than in parental HA22T cells. Mimics of miR-342-5p enhanced apoptosis through upregulation of Bax, cyto-C, cleaved-caspase-3 expressions with concomitant decline in anti-apoptotic protein (Bcl-2) in HDACi-R cells. Although HDACi did not increase cell viability of HDACi-R, overexpression of miR-342-5p decreased cofilin-1 expression, upregulated reactive oxygen species (ROS) mediated apoptosis, and sensitized HDACi-R to HDACi in a dose-dependent manner. CONCLUSION: Our findings demonstrated the critical role of miR-342-5p in HDACi resistance of HCC and that this mechanism might be attributed to miR-342-5p/cofilin-1 regulation.

Evolutionary Design of Self-Templated Supramolecular Fibrils Using M13 Bacteriophage for Tissue Engineering.

Biomaterials in nature form hierarchical structures and functions across various length scales through binding and assembly processes. Inspired by nature, we developed hierarchically organized tissue engineering materials through evolutionary screening and self-templating assembly. Leveraging the M13 bacteriophage (phage), we employed an evolutionary selection process against hydroxyapatite (HA) to isolate HA-binding phage (HAPh). The newly discovered phage exhibits a bimodal length, comprising 950 nm and 240 nm, where the synergistic effect of these dual lengths promotes the formation of supramolecular fibrils with periodic banded structures. The assembled HAPh fibrils show the capability of HA mineralization and the directional growth of osteoblast cells. When applied to a dentin surface, it induces the regeneration of dentin-like tissue structures, showcasing its potential applications as a scaffold in tissue engineering. The integration of evolutionary screening and self-templating assembly holds promise for the future development of hierarchically organized tissue engineering materials.

The function of the inter-alpha-trypsin inhibitors in the development of disease.

Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies.

Crystal structure of the 1:1 co-crystal 4-(di-methylamino)-pyridin-1-ium 8-hy-droxy-quinoline-5-sulfonate-N,N-di-methyl-pyridin-4-amine.

The asymmetric unit of the title compound is composed of two independent ion pairs of 4-(di-methyl-amino)-pyridin-1-ium 8-hy-droxy-quinoline-5-sulfonate (HDMAP+·HqSA-, C7H11N2 +·C9H6NO4S-) and neutral N,N-di-methyl-pyridin-4-amine mol-ecules (DMAP, C7H10N2), co-crystallized as a 1:1:1 HDMAP+:HqSA-:DMAP adduct in the monoclinic system, space group Pc. The compound has a layered structure, including cation layers of HDMAP+ with DMAP and anion layers of HqSA- in the crystal. In the cation layer, there are inter-molecular N-H⋯N hydrogen bonds between the protonated HDMAP+ mol-ecule and the neutral DMAP mol-ecule. In the anion layer, each HqSA- is surrounded by other six HqSA-, where the planar network structure is formed by inter-molecular O-H⋯O and C-H⋯O hydrogen bonds. The cation and anion layers are linked by inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions.

Development of cashew-alginate microbeads and powdered dose forms: prospects for oral vaccine delivery in chickens.

Conventional oral vaccine delivery in poultry is challenging due to vaccine degradation in the gastrointestinal (GI) environment and the need for cold-chain storage. Microencapsulation offers a solution by protecting vaccines from GI degradation and improving stability. Natural polymers like alginate and cashew gum have mucoadhesive properties, making them promising candidates for oral vaccine delivery. This study developed cashew-alginate microbeads and a powdered dose form for oral vaccine delivery in chickens. The microbeads were created using ionotropic gelation, while the powdered form was obtained via freeze-drying. These formulations were characterized for size, shape, and stability using scanning electron microscopy (SEM), light microscopy, X-ray diffraction (XRD), and Energy Dispersive X-ray (EDX). Peak adhesion time (PAT) was determined using chicken intestinal and esophageal tissues, and antigenicity was assessed with in-vitro hemagglutination (HA) and hemagglutination inhibition (HI) assays. The microbeads exhibited a spherical shape with a porous structure, suggesting enhanced antigen accommodation. Hemagglutination Inhibition tests indicated that the experimental vaccine remained effective without cold-chain storage for three months. These findings suggest that cashew-alginate microbeads are promising for oral vaccine delivery in poultry.

Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179 Prolong Lifespan and Mitigate Amyloid-ß Toxicity in C. elegans via Distinct Mechanisms.

Background: Recent advances linking gut dysbiosis with neurocognitive disorders such as Alzheimer's disease (AD) suggest that the microbiota-gut-brain axis could be targeted for AD prevention, management, or treatment. Objective: We sought to identify probiotics that can delay Aß-induced paralysis. Methods: Using C. elegans expressing human amyloid-ß (Aß)1-42 in body wall muscles (GMC101), we assessed the effects of several probiotic strains on paralysis. Results: We found that Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179, but not their supernatants or heat-treated forms, delayed paralysis and prolonged lifespan without affecting the levels of amyloid-ß aggregates. To uncover the mechanism involved, we explored the role of two known pathways involved in neurogenerative diseases, namely mitophagy, via deletion of the mitophagy factor PINK-1, and fatty acid desaturation, via deletion of the Δ9 desaturase FAT-5. Pink-1 deletion in GMC101 worms did not modify the life-prolonging and anti-paralysis effects of HA-114 but reduced the protective effect of R0179 against paralysis without affecting its life-prolonging effect. Upon fat5 deletion in GMC101 worms, the monounsaturated C14:1 and C16:1 FAs conserved their beneficial effect while the saturated C14:0 and C16:0 FAs did not. The beneficial effects of R0179 on both lifespan and paralysis remained unaffected by fat-5 deletion, while the beneficial effect of HA-114 on paralysis and lifespan was significantly reduced. Conclusions: Collectively with clinical and preclinical evidence in other models, our results suggest that HA-114 or R0179 could be studied as potential therapeutical adjuncts in neurodegenerative diseases such as AD.

Selection of appropriate location based on signed distance based ranking approach with interval type-2 trapezoidal fuzzy preference relations.

In real life situation, it is often difficult to judge the relative importance of different parameters being considered for evaluating some alternatives. In the context of fuzzy sets, it is a situation where it is difficult to define precise membership grades for attribute values. Here we require more generalized type of fuzzy sets which have a greater representational power than ordinary fuzzy sets. For this purpose we use "interval type-2 trapezoidal fuzzy preference relations (IT2TrFPRs)" in this article as a generalization of fuzzy preference relations and consider the environment discussed above, where there is no information on priority weights. A collective decision matrix will be constructed on the basis of hybrid averages using weighted averaging and signed distance based OWA operation. Then a least deviation model will be employed in order to determine the priority weight vectors. Finally, the alternatives will be ranked on the basis of weighted normalized signed distance of each alternative from the ideal solution. Moreover, a real life example of location selection is illustrated to elaborate the effectiveness of the proposed scheme.

Effect of Platelet-Rich Fibrin Combined With Hyaluronic Acid on Bone Formation in Dental Implant Sockets: An In Vivo Study in Sheep.

OBJECTIVES: The goal was to evaluate the effect of the combined growth factor of hyaluronic acid (HA) and advanced platelet-rich fibrin (A-PRF) on acceleration and maturation of bone formation around titanium dental implants in the bone-free space (jumping distance) of an over-preparation socket. MATERIALS AND METHODS:  Thirty-two titanium dental implants were placed in four sheep and distributed into one control group (A) and three experimental groups (B, C, and D) in two different time periods. Each sheep received eight implants. The eight implants in each sheep were distributed into four groups. The first period was one month after the initial placement, 16 implants were used in two sheep. The second period was three months after the initial placement; another 16 implants were used in the other two sheep. All implants were placed in over-prepared implant sockets, resulting in minimal primary stability. In Group A: the space between the dental implant and the bone of the inner wall of the socket was left without a growth substrate material. In Group B: we added HA between the dental implant and the bone of the inner wall of the socket. In Group C: we added A-PRF between the dental implant and the bone of the inner wall of the socket. In Group D: we added a combination of HA and A-PRF between the dental implant and the bone of the inner wall of the socket. Data was collected for each group at one month and three months at the same time. A high-resolution, desktop micro-CT system (Bruker Skyscan 1275, Kontich, Belgium) was used to scan the specimens. The NRecon software (ver. 1.6.10.4, SkyScan) and CTAn (SkyScan) were used for the visualization and quantitative measurement of the samples. One-way analysis of variance (ANOVA) was used to compare the means of the four study groups in the same period. A post hoc test was used after ANOVA to compare the means of two samples at the same time. A p-value of ≤ 0.05 was considered statistically significant. RESULTS: After one month and three months of using combined HA and A-PRF on Group D, significant acceleration was observed in bone formation in all tests around dental implants compared with other groups, while no significant acceleration was observed when they were used separately; all three study groups showed significant results when compared with the control group. CONCLUSION: Our data showed that using a combination of HA and A-PRF had a significant effect on the acceleration of the bone formation and ossification process when added to bone-free space (jumping distance) around implants while leaving space without any growth substrates might delay the bone ossification process.

Comparison of the use of biocompatible materials and titanium in the treatment of midshaft clavicle fractures with a patient-specific plate: a finite element analysis study.

BACKGROUND: Clavicular midshaft fractures treated with titanium plates may encounter complications like implant failure. We assess if alternative biocompatible materials suchs as PLA, PLA/HA, PEEK offer comparable stability. Our study evaluates the biomechanical performance of these materials in surgical management of midshaft clavicle fractures. METHODS: We simulated a personalized fixation implant with four different materials and conducted finite element analysis in ANSYS to assess maximum von Mises stress (MvMs). RESULTS: The MvMs occurring on the plates, screws, clavicle, and fracture site were recorded. MvMs on titanium material at the 6th hole level (764.79 MPa) and the 6th screw level (503.38 MPa), with the highest stresses observed at 48.52 MPa on the lateral clavicle at the 1st hole level and 182.27 MPa on the medial clavicle at the 6th hole level. In PLA material analyses, the highest MvMs were observed at the 3rd hole level (340.6 MPa) and the 3rd screw level (157.83 MPa), with peak stresses at 379.63 MPa on the lateral clavicle fracture line and 505.44 MPa on the medial clavicle fracture line. In PLA/HA material analyses, the highest MvMs were at the 3rd hole (295.99 MPa) and 3rd screw (128.27 MPa), with peak stresses at 220.33 MPa on the lateral clavicle and 229.63 MPa on the medial clavicle fracture line. In PEEK material analyses, the highest MvMs were at the 3rd hole (234.74 MPa) and 6th screw (114.48 MPa), with peak stresses at 184.36 MPa on the lateral clavicle and 180.1 MPa on the medial clavicle. CONCLUSION: Our findings indicate that titanium material shows significantly higher stresses on plates and screws compared to those on the clavicle, suggesting a risk of implant failure. PLA and PLA/HA were inadequate for fixation. Although stress on the plate with PEEK material is higher than on the clavicle, it remains lower than titanium, indicating potential stability at fracture site. Further research is needed to confirm these findings.

CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity.

Central and peripheral nervous system (CNS/PNS) proteoglycans (PGs) have diverse functional roles, this study examined how these control cellular behavior and tissue function. The CNS/PNS extracellular matrix (ECM) is a dynamic, responsive, highly interactive, space-filling, cell supportive, stabilizing structure maintaining tissue compartments, ionic microenvironments, and microgradients that regulate neuronal activity and maintain the neuron in an optimal ionic microenvironment. The CNS/PNS contains a high glycosaminoglycan content (60% hyaluronan, HA) and a diverse range of stabilizing PGs. Immobilization of HA in brain tissues by HA interactive hyalectan PGs preserves tissue hydration and neuronal activity, a paucity of HA in brain tissues results in a pro-convulsant epileptic phenotype. Diverse CS, KS, and HSPGs stabilize the blood-brain barrier and neurovascular unit, provide smart gel neurotransmitter neuron vesicle storage and delivery, organize the neuromuscular junction basement membrane, and provide motor neuron synaptic plasticity, and photoreceptor and neuron synaptic functions. PG-HA networks maintain ionic fluxes and microgradients and tissue compartments that contribute to membrane polarization dynamics essential to neuronal activation and neurotransduction. Hyalectans form neuroprotective perineuronal nets contributing to synaptic plasticity, memory, and cognitive learning. Sialoglycoprotein associated with cones and rods (SPACRCAN), an HA binding CSPG, stabilizes the inter-photoreceptor ECM. HSPGs pikachurin and eyes shut stabilize the photoreceptor synapse aiding in phototransduction and neurotransduction with retinal bipolar neurons crucial to visual acuity. This is achieved through Laminin G motifs in pikachurin, eyes shut, and neurexins that interact with the dystroglycan-cytoskeleton-ECM-stabilizing synaptic interconnections, neuronal interactive specificity, and co-ordination of regulatory action potentials in neural networks.

A Computationally Optimized Broadly Reactive Hemagglutinin and Neuraminidase Vaccine Boosts Antibody-Secreting Cells and Induces a Robust Serological Response, Preventing Lung Damage in a Pre-Immune Model.

The hemagglutinin (HA) and neuraminidase (NA) surface proteins are the primary and secondary immune targets for most influenza vaccines. In this study, H2, H5, H7, N1, and N2 antigens designed by the computationally optimized broadly reactive antigen (COBRA) methodology were incorporated into an adjuvant-formulated vaccine to assess the protective efficacy and immune response against A/Hong Kong/125/2017 H7N9 virus challenge in pre-immune mice. The elicited antibodies bound to H2, H5, H7, N1, and N2 wild-type antigens; cH6/1 antigens; and cH7/3 antigens, with hemagglutinin inhibition (HAI) activity against broad panels of the H2Nx, H5Nx, and H7Nx influenza strains. Mice vaccinated with the pentavalent COBRA HA/NA vaccine showed little to no weight loss, no clinical signs of diseases, and were protected from mortality when challenged with the lethal H7N9 virus. Virus titers in the lungs of vaccinated mice were lower and cleared more rapidly than in mock-vaccinated mice. Some vaccinated mice showed no detectable lung injury or inflammation. Antibody-secreting cells were significantly increased in COBRA-vaccinated mice, with higher total Ig and H7-specific ASC. Thus, the combination of H2, H5, H7, N1, and N2 COBRA antigens presents a potential for the formulation of a universal influenza virus vaccine.

Targeting hyaluronan metabolism-related molecules associated with resistant tumor-initiating cells potentiates chemotherapy efficacy in lung cancer.

The success of chemotherapy regimens in patients with non-small cell lung cancer (NSCLC) could be restricted at least in part by cancer stem cells (CSC) niches within the tumor microenvironment (TME). CSC express CD133, CD44, CD47, and SOX2, among other markers and factors. Analysis of public data revealed that high expression of hyaluronan (HA), the main glycosaminoglycan of TME, correlated positively with CSC phenotype and decreased disease-free interval in NSCLC patients. We aimed to cross-validate these findings on human and murine lung cancer cells and observed that CD133 + CSC differentially expressed higher levels of HA, HAS3, ABCC5, SOX2, and CD47 (p < 0.01). We modulated HA expression with 4-methylumbelliferone (4Mu) and detected an increase in sensitivity to paclitaxel (Pa). We evaluated the effect of 4Mu + chemotherapy on survival, HA metabolism, and CSC profile. The combination of 4Mu with Pa reduced the clonogenic and tumor-forming ability of CSC. Pa-induced HAS3, ABCC5, SOX2, and CD47 expression was mitigated by 4Mu. Pa + 4Mu combination significantly reduced in vivo tumor growth, enhancing animal survival and restoring the CSC profile in the TME to basal levels. Our results suggest that HA is involved in lung CSC phenotype and chemosensitivity, and its modulation by 4Mu improves treatment efficacy to inhibit tumor progression.