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In addition, CYP1A2 KO rats exhibited a significant increase in serum cholesterol and free testosterone, accompanied by mild liver damage and lipid deposition, suggesting CYP1A2 deficiency affects lipid metabolism and liver function in rats to some extent. In summary, we successfully constructed the CYP1A2 KO rat model, which provides a useful tool for studying the metabolic function and physiological function of CYP1A2. Significance Statement Human CYP1A2 not only metabolizes clinical drugs and pollutants, but also mediates the biotransformation of endogenous substances, and plays an important role in the development of many diseases. However, there are no relevant CYP1A2 rat models for the research of pharmacokinetics and diseases. This study successfully established CYP1A2 knockout rat model by using CRISPR/Cas9. This rat model provides a powerful tool to study the function of CYP1A2 in drug metabolism and diseases.Recent advances in gene editing technologies are enabling the potential correction of devastating monogenic disorders through elimination of underlying genetic mutations. Duchenne muscular dystrophy (DMD) is an especially severe genetic disorder caused by mutations in the gene encoding dystrophin, a membrane-associated protein required for maintenance of muscle structure and function. Patients with DMD succumb to loss of mobility early in life, culminating in premature death from cardiac and respiratory failure. The disease has thus far defied all curative strategies. CRISPR gene editing has provided new opportunities to ameliorate the disease by eliminating DMD mutations and thereby restore dystrophin expression throughout skeletal and cardiac muscle. Proof-of-concept studies in rodents, large mammals, and human cells have validated the potential of this approach, but numerous challenges remain to be addressed, including optimization of gene editing, delivery of gene editing components throughout the musculature, and mitigation of possible immune responses. This paper provides an overview of recent work from our laboratory and others toward the genetic correction of DMD and considers the opportunities and challenges in the path to clinical translation. Lessons learned from these studies will undoubtedly enable further applications of gene editing to numerous other diseases of muscle and other tissues.We previously reported genotype-phenotype correlations in 12 missense variants causing severe insulin resistance, located in the second and third fibronectin type III (FnIII) domains of the insulin receptor (INSR), containing the α-β cleavage and part of insulin-binding sites. This study aimed to identify genotype-phenotype correlations in FnIII domain variants of IGF1R, a structurally related homolog of INSR, which may be associated with growth retardation, using the recently reported crystal structures of IGF1R. A structural bioinformatics analysis of five previously reported disease-associated heterozygous missense variants and a likely benign variant in the FnIII domains of IGF1R predicted that the disease-associated variants would severely impair the hydrophobic core formation and stability of the FnIII domains or affect the α-β cleavage site, while the likely benign variant would not affect the folding of the domains. A functional analysis of these variants in CHO cells showed impaired receptor processing and autophosphorylation in cells expressing the disease-associated variants but not in those expressing the wild-type form or the likely benign variant. These results demonstrated genotype-phenotype correlations in the FnIII domain variants of IGF1R, which are presumably consistent with those of INSR and would help in the early diagnosis of patients with disease-associated IGF1R variants.At the time of discharge from the NICU, many infants have ongoing complex medical issues that will require coordinated, multispecialty follow-up. Discharge planning and transfer of care for infants with medical complexity require a multidisciplinary team effort that begins early during the NICU hospitalization. It is critical that the primary care physician is involved in this process because he or she will serve as the chief communicator and coordinator of care after discharge. Although some infants with medical complexity may be followed in specialized multidisciplinary NICU follow-up clinics, these are not universally available. The responsibility then falls to the primary care physician to coordinate with different subspecialties based on the infant's needs. Many infants with medical complexity are technology-dependent at the time of discharge and may require home oxygen, ventilators, monitors, or tube feeding. Prematurity, critical illness, and prolonged NICU hospitalization that lead to medical complexity also increase the risk of neurodevelopmental delay or impairment. Dihydromyricetin As such, these infants will not only require routine developmental surveillance and screening by the primary care physician but also should be followed longitudinally by a neurodevelopmental specialist, either a developmental-behavioral pediatrician or a neonatologist with experience in neurodevelopmental assessment.Verinurad is a selective URAT1 inhibitor in development for the treatment of chronic kidney disease and heart failure. In humans, two major acyl glucuronide metabolites have been identified direct glucuronide M1 and N-oxide glucuronide M8. Using in vitro systems recommended by regulatory agencies, we evaluated the interactions of verinurad, M1, and M8 with major drug metabolizing enzymes and transporters and the potential for clinically relevant drug-drug interactions (DDIs). The IC50 for inhibition of CYP2C8, CYP2C9, and CYP3A4/5 for verinurad was greater than or equal to14.5 µM, and Iu,max/IC50 was less then 0.02 at the anticipated therapeutic Cmax and therefore was not considered a DDI risk. Verinurad was not an inducer of CYP1A2, CYP2B6, or CYP3A4/5. Verinurad was identified as a substrate of the hepatic uptake transporter OATP1B3. Since verinurad hepatic uptake involved both active and passive transport, there is a low risk of clinically relevant DDIs with OATP and further study is warranted. Verinurad was a substrate of the efflux transporters P‑glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and renal transporter organic anion transporter 1 (OAT1), although it is not considered a DDI risk in vivo due to dose-proportional pharmacokinetics (P-gp and BCRP) and limited renal excretion of verinurad (OAT1).