Therefore, it will be a preferable means to interfere with nNOS-mediated protein-protein interactions (PPIs), which do not lead to undesirable effects. Herein, we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders, and the discovery of drugs targeting the PPIs, which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.There are an estimated 10 000 monogenic diseases affecting tens of millions of individuals worldwide. The application of CRISPR/Cas genome editing tools to treat monogenic diseases is an emerging strategy with the potential to generate personalized treatment approaches for these patients. CRISPR/Cas-based systems are programmable and sequence-specific genome editing tools with the capacity to generate base pair resolution manipulations to DNA or RNA. The complexity of genomic insults resulting in heritable disease requires patient-specific genome editing strategies with consideration of DNA repair pathways, and CRISPR/Cas systems of different types, species, and those with additional enzymatic capacity and/or delivery methods. In this review we aim to discuss broad and multifaceted therapeutic applications of CRISPR/Cas gene editing systems including in harnessing of homology directed repair, non-homologous end joining, microhomology-mediated end joining, and base editing to permanently correct diverse monogenic diseases. Although endoscopic transpapillary gallbladder drainage (ETGBD) has been reported as an alternative procedure for acute cholecystitis, it requires advanced endoscopic techniques. In terms of the certainty of achieving drainage, it remains a challenging procedure. The aim of the current study was to elucidate the practical efficacy of cholangioscopic assistance and to develop a new classification that could be used to evaluate the technical difficulty of ETGBD and provide a theoretical strategy to apply cholangioscopy appropriately for difficult ETGBD. A total of 101 patients undergoing ETGBD were retrospectively studied. The characteristics and technical outcomes of ETGBD with conventional ETGBD (C-ETGBD) and SpyGlass DS-assisted ETGBD (SG-ETGBD) were evaluated. The characteristics and technique-dependent factors of unsuccessful C-ETGBD/SG-ETGBD were evaluated using the classification based on the steps of the procedure. The predictive factors of successful C-ETGBD/SG-ETGBD were examined. C-ETGBD was su theoretical strategy to apply cholangioscopy in a coordinated manner. The global trend of an expanding aged population has increased concerns about complications correlated with gastrointestinal (GI) endoscopy in elderly patients; however, there have been few reports published on this issue. In this retrospective, observational cohort study performed between 2012 and 2017, serious complications of esophagogastroduodenoscopy (EGD), colonoscopy, and colonoscopic polypectomy were compared between patients according to age (≥65 years vs 18&#8211;64 years). We used the Health Insurance Review and Assessment-National Patient Samples database, previously converted to the standardized Observational Medical Outcomes Partnership-Common Data Model. Serious complications within 30 days of the procedure included both GI complications (bleeding and perforation) and non-GI complications (cerebrovascular accident [CVA], acute myocardial infarction [AMI], congestive heart failure [CHF], and death). A total of 387,647 patients who underwent EGD, 241,094 who underwent colonoscopy, and 89,059 who underwent colonoscopic polypectomy were assessed as part of this investigation. During the study period, endoscopic procedures in the older group steadily increased in number in all endoscopy groups (all p<0.001). Further, pooled complication rates of bleeding, CVA, AMI, CHF, and death were approximately three times higher among older patients who underwent EGD or colonoscopy. Moreover, pooled complication rates of CVA, AMI, CHF, and death were approximately 2.2 to 5.0 times higher among older patients who underwent colonoscopic polypectomy. Elderly patients experienced approximately three times more GI and non-GI complications after EGD or colonoscopy than young patients. Physicians should pay attention to the potential risks of GI endoscopy in elderly patients.Elderly patients experienced approximately three times more GI and non-GI complications after EGD or colonoscopy than young patients. Physicians should pay attention to the potential risks of GI endoscopy in elderly patients.Streptococcus gallolyticus subsp. gallolyticus is an emerging opportunistic pathogen responsible for septicemia and endocarditis in the elderly. Invasive infections by S. gallolyticus subsp. gallolyticus are strongly linked to the occurrence of colorectal cancer (CRC). It was previously shown that increased secondary bile salts under CRC conditions enhance the bactericidal activity of gallocin, a bacteriocin produced by S. gallolyticus subsp. gallolyticus, enabling it to colonize the mouse colon by outcompeting resident enterococci (L. Aymeric, F. Donnadieu, C. Mulet, L. du Merle, et al., Proc Natl Acad Sci U S A 115E283-E291, 2018, https//doi.org/10.1073/pnas.1715112115). In a separate study, we showed that S. gallolyticus subsp. EN450 in vivo gallolyticus produces and secretes a 21-mer peptide that activates bacteriocin production (A. Proutière, L. du Merle, B. Périchon, H. Varet, et al., mBio 11e03187-20, 2020, https//doi.org/10.1128/mBio.03187-20). This peptide was named CSP because of its sequence similarity with compe can be removed (residues 1 to 9) without significantly impacting the peptide activity.IMPORTANCEStreptococcus gallolyticus subsp. gallolyticus is an opportunistic pathogen associated with colorectal cancer (CRC) and endocarditis. S. gallolyticus subsp. gallolyticus utilizes quorum sensing (QS) to regulate the production of a bacteriocin (gallocin) and gain a selective advantage in colonizing the colon. In this article, we report (i) the first structure-activity relationship study of the S. gallolyticus subsp. gallolyticus QS pheromone that regulates gallocin production, (ii) evidence that the active QS pheromone is processed to its mature form by a unique ABC transporter and not processed by an extracellular protease, and (iii) supporting evidence of interspecies interactions between streptococcal pheromones. Our results revealed the minimal pheromone scaffold needed for gallocin activation and uncovered unique interactions between two streptococcal QS signals that warrant further study.