Low-intensity focused ultrasound ameliorates depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway.

It is of great social significance and clinical value to explore new effective treatments for depression. Low-intensity focused ultrasound stimulation (LIFUS) has been indicated to have notable neuroprotective effects on depression. However, little is known about how different strategies of LIFUS affect the therapeutic effect. Therefore, the purpose of this study is to investigate whether the effects of LIFUS on depression-like behaviors are associated with the intensity and the underlying mechanisms. We established the depression rats model using the chronic unpredictable stress (CUS) and applied the LIFUS with high/low intensity (Ispta = 500 and 230 mW/cm2, respectively) to the left medial prefrontal cortex (mPFC) after CUS. We found that two intensities of LIFUS both could significantly improve depression-like behaviors to a comparable degree. We further found that theta oscillation synchronization and synaptic functional plasticity in the hippocampal vCA1-mPFC pathway were significantly improved by chronic LIFUS which mainly due to the alternation of synaptic structural plasticity and the expression of post-synaptic proteins in the mPFC. These results suggest that LIFUS ameliorates the depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway. Our study provides preclinical evidence and a theoretical basis for applying LIFUS for depression treatment.

Progress of research in the application of ultrasound technology for the treatment of Alzheimer's disease.

Alzheimer's disease is a common neurodegenerative disorder defined by decreased reasoning abilities, memory loss, and cognitive deterioration. The presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer's disease. The use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent years. As a safe and feasible therapeutic and drug-delivery method, ultrasound has shown promise in improving cognitive deficits. This article provides a summary of the application of ultrasound technology for treating Alzheimer's disease over the past 5 years, including standalone ultrasound treatment, ultrasound combined with microbubbles or drug therapy, and magnetic resonance imaging-guided focused ultrasound therapy. Emphasis is placed on the benefits of introducing these treatment methods and their potential mechanisms. We found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-ß plaque deposition. We believe that ultrasound is an effective therapy for Alzheimer's disease, and this review provides a theoretical basis for future ultrasound treatment methods.

Closed-Loop Polymer-to-Polymer Upcycling of Waste Poly (Ethylene Terephthalate) into Biodegradable and Programmable Materials.

Poly(ethylene terephthalate) (PET), extensively employed in bottles, film, and fiber manufacture, has generated persistent environmental contamination due to its non-degradable nature. The resolution of this issue requires the conversion of waste PET into valuable products, often achieved through depolymerization into monomers. However, the laborious purification procedures involved in the extraction of monomers pose challenges and constraints on the complete utilization of PET. Herein, a strategy is demonstrated for the polymer-to-polymer upcycling of waste PET into high-value biodegradable and programmable materials named PEXT. This process involves reversible transesterifications dependent on ester bonds, wherein commercially available X-monomers from aliphatic diacids and diols are introduced, utilizing existing industrial equipment for complete PET utilization. PEXT features a programmable molecular structure, delivering tailored mechanical, thermal, and biodegradation performance. Notably, PEXT exhibits superior mechanical performance, with a maximal elongation at break of 3419.2 % and a toughness of 270.79 MJ m-3. These characteristics make PEXT suitable for numerous applications, including shape-memory materials, transparent films, and fracture-resistant stretchable components. Significantly, PEXT allows closed-loop recycling within specific biodegradable analogs by reprograming PET or X-monomers. This strategy not only offers cost-effective advantages in large-scale upcycling of waste PET into advanced materials but also demonstrates its enormous prospect in environmental conservation.

A simple hydrogel scaffold with injectability, adhesivity and osteogenic activity for bone regeneration.

Numerous efforts have been made to prepare hydrogels with injectability, adhesivity and osteogenic activity for bone regeneration. However, current hydrogels with these characteristics have limited application in clinical translation due to their complex chemical compositions, which causes difficulty in batch production. In this study, a multifunctional hydrogel with a binary component is prepared for bone regeneration. Dopamine (DA) is first grafted to alginate (Alg) by amidation reaction to give Alg-DA. Then an injectable hydrogel is facilely prepared by mixing strontium ions with the Alg-DA aqueous solution, utilizing the dynamic ionic bonds between the strontium ions and carboxyl groups of Alg-DA. Under the simulated oxidation conditions in vivo, the injectable hydrogel can form stable chemical crosslinkages owing to the presence of catechol groups on Alg-DA. In addition, the catechol groups endow the hydrogel with significant tissue adhesivity. More importantly, the strontium ions endow the hydrogel with osteogenic activity. As indicated by animal experiments, the strontium containing hydrogel scaffolds help to treat rat bone defects within 8 weeks compared to hydrogels without strontium and control groups. This simple hydrogel constructed by using a binary component has achieved several necessary functions, and is expected to be used as a scaffold for bone tissue engineering in clinical applications.

Reduction-Responsive Anticancer Nanodrug Using a Full Poly(ethylene glycol) Carrier.

Poly(ethylene glycol) (PEG) is applied extensively in biomedical fields because of its nontoxic, nonimmunogenic, and protein resistance properties. However, the strong hydrophilicity of PEG prevents it from self-assembling into an amphiphilic micelle in water, making it a challenge to fabricate a full-PEG carrier to deliver hydrophobic anticancer drugs. Herein, a paclitaxel (PTX)-loaded nanodrug was readily prepared through self-assembly of PTX and an amphiphilic PEG derivative, which was synthesized via melt polycondensation of two PEG diols (i.e., PEG200 and PEG10k) and mercaptosuccinic acid. The full PEG component endows the nanocarrier with good biocompatibility. Furthermore, because of the core cross-linked structure via the oxidation of mercapto groups, the nanodrug can be selectively disassociated under an intratumor reductive microenvironment through the reduction of disulfide bonds to release the loaded PTX and kill the cancer cells while maintaining high stability under the extratumor physiological condition. Additionally, it was confirmed that the nanodrug not only prolongs the biocirculation time of PTX but also possesses excellent in vivo antitumor efficacy while avoiding side effects of free PTX, for example, liver damage, which is promising for delivering clinical hydrophobic drugs to treat a variety of malignant tumors.

Full Poly(ethylene glycol) Hydrogels with High Ductility and Self-Recoverability.

Energy dissipation is a common mechanism to improve the ductility of polymeric hydrogels. However, for poly(ethylene glycol) (PEG) hydrogels, it is not easy to dissipate energy, as polymer chains are dispersed in water without strong interchain interactions or decent entanglement. The brittleness limits the real applications of PEG hydrogels, although they are promising candidates in biomedical fields, as PEG has been approved by the U.S. Food and Drug Administration. Herein, we chemically introduced a center for energy dissipation in the PEG hydrogel system. Amphiphilic segmented PEG derivatives were designed through the melt polycondensation of triethylene glycol (PEG150) and high molecular weight PEG in the presence of succinic acid and mercaptosuccinic acid as dicarboxylic acids. Full PEG hydrogels with elastic nanospheres as giant cross-linkers were facilely prepared by the self-assembly of esterified PEG150 segments and the oxidation of mercapto groups. The resultant full PEG hydrogels can dissipate energy by the deformation of elastic nanospheres with outstanding ductility and self-recoverability while maintaining the excellent biocompatibility owing to their full PEG components. This work provides an original strategy to fabricate full PEG hydrogels with high ductility and self-recoverability, potentially applicable in biomedical fields.

A shear-thinning electrostatic hydrogel with antibacterial activity by nanoengineering of polyelectrolytes.

Injectable shear-thinning hydrogels can be prepared by the non-covalent interactions between hydrophilic polymers. Although electrostatic force is a typical non-covalent interaction, direct mixing of two oppositely charged polyelectrolytes usually leads to a complex coacervate rather than an injectable hydrogel. Herein, a facile approach is proposed to prepare a shear-thinning hydrogel by nanoengineering of polyelectrolytes. Nanosized cationic micelles with electroneutral shells were prepared by mixing methoxyl poly(ethylene glycol)-block-poly(ε-caprolactone) and poly(ε-caprolactone)-block-poly(hexamethylene guanidine) hydrochloride-block-poly(ε-caprolactone) in an aqueous solution. When sodium carboxymethyl cellulose was added into the micellar solution, the outer poly(ethylene glycol) shell of mixed micelles prevented the instant electrostatic interaction between poly(hexamethylene guanidine) hydrochloride segments and sodium carboxymethyl cellulose, resulting in a homogenous shear-thinning electrostatic (STES) hydrogel. Because of the cationic poly(hexamethylene guanidine) hydrochloride segments, this hydrogel exhibits strong antibacterial activity against both Gram-positive and Gram-negative bacteria. Furthermore, the poly(ε-caprolactone) core of the mixed micelles can efficiently encapsulate a hydrophobic drug. In this work, curcumin-loaded STES hydrogel prepared by this method was used as wound dressing material that can promote wound healing even in infected wounds by further reducing bacterial infection via releasing curcumin. The present study provides a facile strategy to prepare shear-thinning antibacterial hydrogels from polyelectrolytes, which has great potential in biomedical application.

Facile and Versatile Modification of Cotton Fibers for Persistent Antibacterial Activity and Enhanced Hygroscopicity.

Natural fibers with functionalities have attracted considerable attention. However, developing facile and versatile strategies to modify natural fibers is still a challenge. In this study, cotton fibers, the most widely used natural fibers, were partially oxidized by sodium periodate in aqueous solution, to give oxidized cotton fibers containing multiple aldehyde groups on their surface. Then poly(hexamethylene guanidine) was chemically grafted onto the oxidized cotton fibers forming Schiff bases between the terminal amines of poly(hexamethylene guanidine) and the aldehyde groups of oxidized cotton fibers. Finally, carbon-nitrogen double bonds were reduced by sodium cyanoborohydride, to bound poly(hexamethylene guanidine) covalently to the surface of cotton fibers. These functionalized fibers show strong and persistent antibacterial activity: complete inhibition against Escherichia coli and Staphylococcus aureus was maintained even after 1000 consecutive washing in distilled water. On the other hand, cotton fibers with only physically adsorbed poly(hexamethylene guanidine) lost their antibacterial activity entirely after a few washes. According to Cell Counting Kit-8 assay and hemolytic analysis, toxicity did not significantly increase after chemical modification. Attributing to the hydrophilicity of poly(hexamethylene guanidine) coatings, the modified cotton fibers were also more hygroscopic compared to untreated cotton fibers, which can improve the comfort of the fabrics made of modified cotton fibers. This study provides a facile and versatile strategy to prepare modified polysaccharide natural fibers with durable antibacterial activity, biosecurity, and comfortable touch.