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This pH-responsive isothermal phase transition facilitated interaction with the cultured cancer cells, accomplishing 8.1 times-enhanced cellular uptake and strong phototoxicity in a tumorous pH-selective manner. Even in subcutaneous tumor models, our polymer conjugates exhibited efficient tumor accumulation and significantly augmented PDT effect without inducing unfavorable photochemical toxicity to the skin. This study offers a novel concept of PS delivery systems targeting tumorous pH by the use of isothermal phase transition.Nucleic acid-based pattern recognition receptor agonists are effective adjuvants and immunotherapeutic agents. Rather than single applications, ligand combinations could synergistically potentiate immune responses by elevating cytokine and chemokine production via triggering multiple signaling pathways. However, short half-lives of such labile ligands due to nuclease attack and limited cellular uptake due to their structure significantly hamper their in vivo performances. selleck products More importantly, simultaneous delivery and activity presentation of protein antigen and nucleic acid ligands critically limit the clinical development of these constructs. In this work, we approached this problem by co-encapsulating a model antigen ovalbumin along with TLR9 and STING ligands within liposomes, a well-established drug delivery system that enables payload stability and enhanced cellular activity upon internalization. Moreover, by loading dual ligands we postulated to achieve heightened Th-1 immune response that would yield pronounced protective vaccine efficacy. We show that, pH-sensitive liposomes co-encapsulating CpG ODN and cGAMP induced synergistic innate immune response by elevating type I and type II interferon levels. Most importantly, this vaccine formulation led to ~70% regression of established melanoma tumor. pH-sensitive liposomal vaccine administration elevated IgG2c/IgG1 antibody ratio, indicative of augmented OVA-specific Th1-biased immunity. Importantly, while the frequency of tumor-specific IFN-γ producing CD8+ T-cells was significantly increased, the M2-type anti-inflammatory macrophage levels were decreased in the tumor bed. In conclusion, our strategy induces reversal of immunosuppressive tumor microenvironment, while enhancing effective anti-tumor immune-response. We propose that this could be coupled with standard therapies during combating tumor eradication.In the past decades, adequate and well-planned management of chronic wounds has reached an elevated importance to improve human's quality of life and extend life expectancy. The need for more complex and biomimetic strategies has fueled the exploration of numerous emerging technologies. However, the development of new therapies requires an extensive knowledge of the wound healing process and the key players involved in it. In that sense, this review seeks to bring researchers an updated description of the wound healing process, combining the traditionally-told phase progression with the presence and function of diverse stem cells and other involved mediators. Furthermore, the present work discusses a wide variety of strategies for accelerating wound healing; from systemic or local dressing-free therapies, to cell-free dressings including films, biopolymeric porous scaffolds, electrospun nanofiber meshes and hydrogels. Finally, emerging therapy solutions derived from the development of 3D bioprinting and CRISPR/Cas9 technology or the application of extracellular vesicles in healing chronic wounds are also discussed.Loss of sensory function is a common consequence of neurological injury. Recent clinical and preclinical evidence indicates vagus nerve stimulation (VNS) paired with tactile rehabilitation, consisting of delivery of a variety of mechanical stimuli to the hyposensitive skin surface, yields substantial and long-lasting recovery of somatosensory function after median and ulnar nerve transection and repair. Here, we tested the hypothesis that a specific component of the tactile rehabilitation paired with VNS is necessary for recovery of somatosensory function. In a second experiment in a separate cohort, we investigated whether VNS paired with tactile rehabilitation could improve skilled forelimb motor function. Elements of the study design, including planned sample size, assessments, and statistical comparisons, were preregistered prior to beginning data collection (https//osf.io/3tm8u/). Animals received a peripheral nerve injury (PNI) causing chronic sensory loss. Eight weeks after injury, animals were given a rehabilitation paired with VNS determine the degree of recovery.During self-guided movements, we optimise performance by combining sensory and self-motion cues optimally, based on their reliability. Discrepancies between such cues and problems in combining them are suggested to underlie some pain conditions. Therefore, we examined whether visuomotor integration is altered in twenty-two participants with upper or lower limb complex regional pain syndrome (CRPS) compared to twenty-four controls. Participants located targets that appeared in the unaffected (CRPS) / dominant (controls) or affected (CRPS) / non-dominant (controls) side of space, using the hand of their unaffected/dominant or affected/non-dominant side of the body. For each side of space and each hand, participants located the target using visual information and no movement (vision only condition), an unseen pointing movement (self-motion only condition), or a visually-guided pointing movement (visuomotor condition). In all four space-by-hand conditions, controls reduced their variability in the visuomotor compared to the vision and self-motion only conditions and in line with a model prediction for optimal integration. Participants with CRPS showed similar evidence of cue combination in two of the four conditions. However, they had better-than-optimal integration for the unaffected hand in the affected space. Furthermore, they did not integrate optimally for the hand of the affected side of the body in unaffected space, but instead relied on the visual information. Our results suggest that people with CRPS can optimally integrate visual and self-motion cues under some conditions, despite lower reliability of self-motion cues, and use different strategies to controls.