Methods are described to reduce risk of or prevent wooden chest syndrome or other respiratory effects arising from exposure to fentanyl or a fentanyl analog, for instances inpatients receiving medically assisted treatment (MAT) for Opioid Use Disorder (OUD) or who are receiving analgesia and pain management with F/FAs. Pharmaceutical compositions for use in such methods are described.

The present invention provides method for monitoring physiological status of an organ in a subject by monitoring morphological changes over time in transplanted tissue on an eye of the subject.

Described herein are donor vectors and systems for use in in vivo dual recombinase-mediated cassette exchange. Also described are animal models for consistent, rigorous, and facile investigation of transgene expression. Further described are methods of screening for therapeutic drugs using these animal models, and methods of treatment.

Methods of identifying a xenohormetic induced phenotype in an organism are provided. Also provided are methods if using organisms having a known xenohormetically induced phenotype in a number of different applications, such as the identification of xenohormetic agents and the generation of chemical entities and foodstuffs under specific conditions of production governed by xenohormetic effects.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

The present invention provides a method of constituting a tissue construct in vitro using a tissue without depending on scaffold materials. A method of integrating a biological tissue with a vascular system in vitro, comprising coculturing a biological tissue with vascular cells and mesenchymal cells. A biological tissue which has been integrated with a vascular system by the above-described method. A method of preparing a tissue or an organ, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of regeneration or function recovery of a tissue or an organ, comprising transplanting the biological tissue described above into a human or a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of preparing a non-human chimeric animal, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or organ in which vascular networks have been constructed. A method of evaluating a drug, comprising using at least one member selected from the group consisting of the biological tissue described above, the tissue or organ prepared by the method described above, and the non-human chimeric animal prepared by the method described above. A composition for regenerative medicine, comprising a biological tissue which has been integrated with a vascular system by the method described above.

The invention provides novel engineered CRISPR/Cas effector enzymes, such as Cas13 (e.g., Cas13e) that substantially maintain guide-sequence-specific endonuclease activity and substantially lack guide-sequence-independent collateral endonuclease activity compared to the corresponding wild-type Cas. Also provided are polynucleotides encoding the same, vectors or host cells comprising the polynucleotides or engineered Cas, and method of use, such as in RNA-based target gene transcript knock down.

The present invention relates to a preparation method for an animal model with Alzheimer's disease by injecting a human mutant tau (AAV-hTau) vector and adenovirus into an animal. The preparation method for an AD animal model provided by the present invention may contribute to the development of the field of treatment technology for treating AD since the preparation method causes AD pathology to appear as early as 8 months old and facilitates studies on AD target treatment strategies and tau pathology.

The present invention relates to compositions and methods of use of anti-ADAMTS13 autoantibodies and fragments thereof. In one aspect, the invention includes a composition comprising an isolated anti-ADAMTS13 autoantibody or fragment thereof. In other aspects, methods are described for generating an in vivo model of thrombotic thrombocytopenic purpura (TTP) comprising introducing at least one anti-ADAMTS13 autoantibody or fragment thereof into a model organism and identifying an anti-autoimmune reagent for treating TTP.

The present application relates to a non-human mammal model of a human neurodegenerative disorder, methods of producing the non-human mammal model, and methods of using the non-human mammal model to identify agents suitable for treating a neurodegenerative disorder. The present application also relates to methods of treating neurodegenerative disorders and restoring normal brain interstitial potassium levels.