Human brain organoid:trends,evolution,and remaining challenges

Advanced brain organoids provide promising platforms for deciphering the cellular and molecular processes of human neural development and diseases.Although various studies and reviews have described developments and advancements in brain organoids,few studies have comprehensively summarized and analyzed the global trends in this area of neuroscience.To identify and further facilitate the development of cerebral organoids,we utilized bibliometrics and visualization methods to analyze the global trends and evolution of brain organoids in the last 10 years.First,annual publications,countries/regions,organizations,journals,authors,co-citations,and keywords relating to brain organoids were identified.The hotspots in this field were also systematically identified.Subsequently,current applications for brain organoids in neuroscience,including human neural development,neural disorders,infectious diseases,regenerative medicine,drug discovery,and toxicity assessment studies,are comprehensively discussed.Towards that end,several considerations regarding the current challenges in brain organoid research and future strategies to advance neuroscience will be presented to further promote their application in neurological research.

Rational design of water-soluble,homotypic keratins self-assembly with enhanced bioactivities

Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and synthesis of water-soluble keratins using a simple methodology named the QTY code.In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200-fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins.Homotypic self-assembly was observed for the first time in recombinant keratins in an aqueous environment,without urea and after QTY modification.Cell and animal experiments showed the in situ gel-forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins.Our work not only presented a simple and feasible pathway to produce large amounts of water-soluble keratins using QTY modification but also validated the enhanced self-assembly,hemostasis,and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.

Nano Calcium-Deficient Hydroxyapatite/O-carboxymethyl Chitosan-CaCl_(2) Microspheres Loadedwith RheinforBone Defect Repair

Glutaraldehyde(GA),the most widely used crosslinking agent for biomaterials,is cytotoxic.CaCl_(2) is of particular interest due to its non-toxic nature.Rhein can chelate Ca^(2+)and promote bone growth.Here we reported a novel nano calcium-deficient hydroxyapatite/O-carboxymethyl chitosan-CaCl_(2) microspheres loaded with rhein(RH-nCDHA/OCMC-CaCl_(2) microspheres)using CaCl_(2) as crosslinking agent for bone defect repair.The obtained microspheres were characterized by X-ray diffraction(XRD),scanning electron microscopy(SEM),thermogravimetric analysis(TG)and Fourier transform infrared spectroscopy(FT-IR).The surface of the obtained microspheres is rough with quite a few voids.The nano calcium-deficient hydroxyapatite(nCDHA)accounts for about 70% of the total weight of the microspheres,which is equivalent to the proportion of inorganic substances in human bones.A high encapsulation efficiency(EE)and loading capacity(LC)of the microspheres loaded with rhein was 90.20±0.60% and 11.03±0.30%,respectively.For microspheres using CaCl_(2) in simulated body fluid(SBF)after 14 days,the drug released continuously and bone-like apatite formed like layer.The cells on the surface of the RH-nCDHA/OCMC-CaCl_(2) microspheres grew better comparing with nCDHA/OCMC-GA microspheres and the skull defects of rats after landfill can be almost repaired after 8 weeks,which revealed the potential of the microspheres for bone repair.

Fabrication of ulcer-adhesive oral keratin hydrogel for gastric ulcer healing in a rat

Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided with endoscopic catheter in most cases.Here,we developed an oral keratin hydrogel to accelerate the ulcer healing without endoscopic guidance,which can specially adhere to the ulcer because of the high-viscosity gel formation on the wound surface in vivo.Approximately 50%of the ulcer-adhesive keratin hydrogel can resident in ethanol-treated rat stomach within 12 h,while approximately 18%of them maintained in health rat stomach in the same amount of time.Furthermore,Keratin hydrogels accelerated the ethanol-induced gastric ulcer healing by stopping the bleeding,preventing the epithelium cells from gastric acid damage,suppressing inflammation and promoting re-epithelization.The oral administration of keratin hydrogel in gastric ulcer treatment can enhance the patient compliance and reduce the gastroscopy complications.Our research findings reveal a promising biomaterial-based approach for treating gastrointestinal ulcers.