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Secondary prevention of skin cancer consists in early detection of malignant lesions through patients’ mole self-examination and medical examination. The objective of this study was to assess the self-reported frequency of mole examination in a large, representative sample of the adult general population of 17 countries from all continents. Of a total of 17,001 participants, 4.8% had their moles checked by a dermatologist more than once a year, 11.3% once a year, 8.4% every 2–3 years, 12.4% once in a while, 10.3% once in lifetime, and 52.6% of participants had never performed a mole examination. Egypt was the country with the highest prevalence of people who performed a moles check more than once a year (15.9%), followed by Brazil and the USA. A higher frequency of mole checks was associated with sex (man vs woman), higher education, higher income, fair phototype, history of skin cancer, medical insurance, and sun-protective behaviours. Despite recommendations by health providers, it appears that the frequency of mole checks in the general population is still low. It is necessary for dermatologists to keep informing at-risk populations about the importance of moles check, with particular care regarding categories that less frequently adhere to secondary prevention measures.

Abstract Seborrheic keratosis (SK) is a common skin disease in the elderly. However, in cases where SK presenting as multiple skin-colored or clustered lesions can be easily misdiagnosed as verruca plana (VP), especially in the young population. This retrospective study investigated the prevalence of SK and VP in the lesions that appear clinically similar to VP according to age. We examined the pathology slides of the skin tissue and photographs of patients who were clinically suspected to have VP. A total of 503 patients were included in the study, out of which 174 patients were finally diagnosed with SK (34.6%) and 132 with VP (26.2%). The mean ages of the SK- and VP-diagnosed group were 39.3 and 35.4 years, respectively. SK had a higher prevalence among individuals older than 30 years, and relative frequency of SK should not be ignored in patients with a grouped distribution in their 20 s and 30 s. Therefore, our study suggests that multiple verrucous skin-colored to brownish plaques are also commonly diagnosed as SK in young people as well as VP, and the prevalence of SK and VP may not always depend solely on chronological aging, and the prevalence of SK among young people may be higher than commonly believed stereotypes suggest.

Abstract Melasma relapse is almost common after discontinuation of conventional treatment. Recent studies suggesting that photoaging dermis is the main pathomechanism of melasma, emphasize the dermal targeting therapy. We investigated maintenance effect of microneedling radiofrequency (RF) for melasma treatment. Subjects with melasma were administered oral tranexamic acid and triple combination cream for 2 months and a randomly assigned half face was treated with RF. After discontinuation of conventional therapy, the half face RF continued monthly over 6 months. Modified melasma area severity index (mMASI) score and L* value by a chromameter were collected monthly. Fifteen subjects were enrolled and eleven completed the 8-month study. At 2nd month of conventional therapy, all subjects showed improvement with a 64% reduction in mMASI score. With continuous RF treatment, the improvement was well maintained; whereas in untreated side, the Δ L* gradually decreased, returning to the baseline after the conventional therapy ended. The continuous microneedling RF therapy is beneficial in maintaining the conventional therapy of melasma suggesting the protective effect of dermal targeting therapy in melasma development. (Clinical Trial registration number: NCT05710068, date of first registration: 02/02/2023).

Abstract The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed “mid-old status” cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.

Natural killer (NK) cells are immune effector cells with outstanding features for adoptive immunotherapy. Immune effector cells with chimeric antigen receptors (CARs) are promising targeted therapeutic agents for various diseases. Because tumor cells exhibit heterogeneous antigen expression and lose cell surface antigen expression during malignant progression, many CARs fixed against only one antigen have limited efficacy and are associated with tumor relapse. To expand the utility of CAR-NK cells, we designed a split and universal cotinine-CAR (Cot-CAR) system, comprising a Cot-conjugator and NK92 cells (α-Cot-NK92 cells) engineered with a CAR containing an anti-Cot-specific single-chain variable fragment and intracellular signaling domain. The efficacy of the Cot-CAR system was assessed in vitro using a cytolysis assay against various tumor cells, and its single- or multiple- utility potential was demonstrated using an in vivo lung metastasis model by injecting A549-Red-Fluc cells. The α-Cot-NK92 cells could switch targets, logically respond to multiple antigens, and tune cytolytic activation through the alteration of conjugators without re-engineering. Therefore the universal Cot-CAR system is useful for enhancing specificity and diversity of antigens, combating relapse, and controlling cytolytic activity. In conclusion, this universal Cot-CAR system reveals that multiple availability and controllability can be generated with a single, integrated system.

Abstract Background A flipped classroom with team-based learning is a blended educational strategy that guides active learning inside and outside the classroom. This study aimed to verify the effects of this innovative blended educational strategy on knowledge, problem-solving ability, and learning satisfaction of undergraduate nursing students undergoing public healthcare education. Methods The subjects were undergraduate nursing students enrolled in H University in South Korea. The experiment was conducted over a period of 8 weeks in the public healthcare course. Two groups, blended learning (A flipped classroom with team-based learning) which was the experimental group and traditional lecture-based classroom group, the control group, were assessed. In the blended learning group, the students had pre-class, in-class (including team-based learning elements), and post-class learning elements. The two groups were compared on the following learning outcomes: knowledge, problem-solving ability, and learning satisfaction. Results Results showed that the blended learning instructional methods, in comparison with traditional lectures, enhanced the students’ knowledge, problem-solving ability, and learning satisfaction in the public healthcare course. Conclusions This study supports the feasibility of the flipped classroom with team-based learning as a blended learning strategy, able to produce improvements in nursing students’ learning outcomes. Blended learning approaches may be an effective alternative to conventional approaches in nursing education.

Objectives: Salmonella enterica Indiana ST17 strain (K16SI097), exclusively found in China, was first isolated in 2016 in Korea from a chicken carcass. This strain contains multidrug-resistant genes, and is particularly resistant to ciprofloxacin (64 μg/mL). In this study, we aimed to elucidate the genomic relationship and compare antimicrobial resistance factors between Korean chicken-derived and Chinese clones of S. Indiana ST17. Methods: The genomic DNA of S. enterica Indiana K16SI097 was sequenced via the combined analysis of 20-kb PacBio SMRTbell library and PacBio RS II. Antimicrobial resistance genes were analysed by the Center for Genomic Epidemiology (http://www.genomicepidemiology.org/). Chromosomal and plasmid DNA of the Korean and Chinese strains were compared. Results: The K16SI097 genome comprises two contiguous sequences (contigs) amounting to 4 731 335 base pairs with a 51.85% GC content. In total, 4574 protein-coding regions, 84 tRNA genes, and 22 rRNA genes were detected. Among the annotated contigs, 14 antimicrobial resistance genes were detected; DNA gyrase and topoisomerase IV contained mutations. Moreover, chromosomal DNA of K16SI097 and of the published Chinese strain displayed 99.9% similarity. Furthermore, plasmids displayed similar sizes, sequences, and structures. Conclusions: This is the first report on the complete genome sequence of the high-level ciprofloxacin-resistant S. enterica Indiana ST17 strain isolated in Korea. This genome sequence will help us understand the ST17 strain lineage and its features such as antimicrobial resistance.

Skin aging is induced and sustained by chronological aging and photoaging. Aging skin pigmentation such as mottled pigmentation (senile lentigo) and melasma are typical signs of photoaging. The skin, like other human organs, undergoes cellular senescence, and senescent cells in the skin increase with age. The crosstalk between melanocytes as pigmentary cells and other adjacent types of aged skin cells such as senescent fibroblasts play a role in skin-aging pigmentation. In this review, we provide an overview of cellular senescence during the skin-aging process. The discussion also includes cellular senescence related to skin-aging pigmentation and the therapeutic potential of regulating the senescence process.

Antimicrobial-resistant bacteria in food animals pose a major public health threat worldwide. In this study, we aimed to assess the antimicrobial resistance profiles and resistance trends of commensal Escherichia coli isolated from the feces of healthy cattle, pigs, and chickens in South Korea during 2010 and 2020. A total of 7237 E. coli isolates (2733 cattle, 2542 pig, and 1962 chicken isolates) were tested for susceptibility towards 12 antimicrobials. About 48%, 90%, and 97% of cattle, pig, and chicken isolates, respectively, were resistant to one or more antimicrobial agents. Cattle isolates presented low resistance (45%) resistance rate to ampicillin, chloramphenicol, streptomycin, and tetracycline. We observed high ciprofloxacin and nalidixic acid resistance rates in chicken (76.1% and 88.6%, respectively), isolates in pig (12.7% and 26.7%, respectively) and cattle (2.7% and 8.2%, respectively) isolates. Notably, a very small proportion of isolates (E. coli isolated from major food animals in Korea to commonly used antimicrobials including critically important antimicrobials. These bacteria could not only be a resistance reservoir but also could have potential to spread this resistance through gene transfer to pathogenic bacteria. Thus, the high prevalence of antimicrobial resistance in food animals highlights the urgent need for measures to restrict and ensure the prudent use of antimicrobials in Korea.

We identified 1218 Campylobacter coli isolates from fecal and carcass samples of pigs (n = 643) and chickens (n = 575) between 2010 and 2018. About 99% of the isolates were resistant to at least one antimicrobial agent. The isolates exhibited high resistance rates (>75%) to ciprofloxacin, nalidixic acid, and tetracycline. Azithromycin and erythromycin resistance rates were the highest in isolates from pigs (39.7% and 39.2%, respectively) compared to those of chickens (15.8% and 16.3%, respectively). Additionally, a low-to-moderate proportion of the isolates were resistant to florfenicol, gentamicin, clindamycin, and telithromycin. Multidrug resistance (MDR) was found in 83.1% of the isolates, and profiles of MDR usually included ciprofloxacin, nalidixic acid, and tetracycline. We found point mutation (A2075G) in domain V of the 23S rRNA gene in the majority of erythromycin-resistant isolates. Multilocus sequence typing of 137 erythromycin-resistant C. coli isolates revealed 37 previously reported sequence types (STs) and 8 novel STs. M192I, A103VI, and G74A substitutions were frequently noted in the ribosomal proteins L4 or L22. Further, we identified a considerable proportion (>90%) of erythromycin-resistant isolates carrying virulence factor genes: flaA, cadF, ceuE, and VirB. The prudent use of antimicrobials and regular microbiological investigation in food animals will be vital in limiting the public health hazards of C. coli in Korea.

Alzheimer’s disease (AD) is the most predominant age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregates of amyloid beta Aβ1–42 and tau hyperphosphorylation in the brain. It is considered to be the primary cause of cognitive dysfunction. The aggregation of Aβ1–42 leads to neuronal inflammation and apoptosis. Since vitamins are basic dietary nutrients that organisms need for their growth, survival, and other metabolic functions, in this study, the underlying neuroprotective mechanism of nicotinamide (NAM) Vitamin B3 against Aβ1–42 -induced neurotoxicity was investigated in mouse brains. Intracerebroventricular (i.c.v.) Aβ1–42 injection elicited neuronal dysfunctions that led to memory impairment and neurodegeneration in mouse brains. After 24 h after Aβ1–42 injection, the mice were treated with NAM (250 mg/kg intraperitoneally) for 1 week. For biochemical and Western blot studies, the mice were directly sacrificed, while for confocal and “immunohistochemical staining”, mice were perfused transcardially with 4% paraformaldehyde. Our biochemical, immunofluorescence, and immunohistochemical results showed that NAM can ameliorate neuronal inflammation and apoptosis by reducing oxidative stress through lowering malondialdehyde and 2,7-dichlorofluorescein levels in an Aβ1–42-injected mouse brains, where the regulation of p-JNK further regulated inflammatory marker proteins (TNF-α, IL-1β, transcription factor NF-kB) and apoptotic marker proteins (Bax, caspase 3, PARP1). Furthermore, NAM + Aβ treatment for 1 week increased the amount of survival neurons and reduced neuronal cell death in Nissl staining. We also analyzed memory dysfunction via behavioral studies and the analysis showed that NAM could prevent Aβ1–42 -induced memory deficits. Collectively, the results of this study suggest that NAM may be a potential preventive and therapeutic candidate for Aβ1–42 -induced reactive oxygen species (ROS)-mediated neuroinflammation, neurodegeneration, and neurotoxicity in an adult mouse model.

Intestinal commensal bacteria are considered good indicators for monitoring antimicrobial resistance. We investigated the antimicrobial resistance profiles and resistance trends of Enterococcus faecium and Enterococcus faecalis isolated from food animals in Korea between 2010 and 2019. E. faecium and E. faecalis, isolated from chickens and pigs, respectively, presented a relatively high resistance rate to most of the tested antimicrobials. We observed high ciprofloxacin (67.9%), tetracycline (61.7%), erythromycin (59.5%), and tylosin (53.0%) resistance in E. faecium isolated from chickens. Similarly, more than half of the E. faecalis isolates from pigs and chickens were resistant to erythromycin, tetracycline and tylosin. Notably, we observed ampicillin, daptomycin, tigecycline and linezolid resistance in a relatively small proportion of enterococcal isolates. Additionally, the enterococcal strains exhibited an increasing but fluctuating resistance trend (p < 0.05) to some of the tested antimicrobials including daptomycin and/or linezolid. E. faecalis showed higher Multidrug resistance (MDR) rates than E. faecium in cattle (19.7% vs. 8.6%, respectively) and pigs (63.6% vs. 15.6%, respectively), whereas a comparable MDR rate (≈60.0%) was noted in E. faecium and E. faecalis isolated from chickens. Collectively, the presence of antimicrobial-resistant Enterococcus in food animals poses a potential risk to public health.

Colistin is considered the last resort for the treatment of multi-drug resistant Gram-negative bacterial infections. We studied colistin resistance and the mcr-1 gene carriage in Salmonella isolates recovered from food animals in South Korea between 2010 and 2018. Colistin resistance was found in 277 isolates, predominantly in Salmonella Enteritidis (57.1%) and Salmonella Gallinarum (41.9%). However, the mcr-1 gene was identified in only one colistin-resistant Salmonella Typhimurium (MIC = 16 µg/mL) isolated from a healthy pig. The mcr-1 carrying isolate presented additional resistance to multiple antimicrobials. The strain belonged to sequence type (ST)19 and carried various virulence factor genes that are associated with adhesion and invasion of Salmonella into intestinal epithelial cells, as well as its survival in macrophages. The mcr-1 gene was identified on an IncI2 plasmid and it was also transferred to the E. coli J53 recipient strain. The mcr-1-carrying plasmid (pK18JST013) in this study was closely related to that previously reported in S. Indiana (pCFSA664-3) from chicken in China. This is the first report of mcr-1 carrying S. Typhimurium in South Korea. The finding indicates the importance of regular screening for the presence of the mcr-1 gene in S. Typhimurium in food animals to prevent the spread to humans.

Altogether, 2547 Staphylococcus aureus isolated from cattle (n = 382), pig (n = 1077), and chicken carcasses (n = 1088) during 2010–2017 were investigated for linezolid resistance and were further characterized using molecular methods. We identified linezolid resistance in only 2.3% of pig carcass isolates. The linezolid-resistant (LR) isolates presented resistance to multiple antimicrobials, including chloramphenicol, clindamycin, and tiamulin. Molecular investigation exhibited no mutations in the 23S ribosomal RNA. Nevertheless, we found mutations in ribosomal proteins rplC (G121A) and rplD (C353T) in one and seven LR strains, respectively. All the LR isolates carried the multi-resistance gene cfr, and six of them co-carried the mecA gene. Additionally, all the LR isolates co-carried the phenicol exporter gene, fexA, and presented a high level of chloramphenicol resistance. LR S. aureus isolates represented 10 genotypes, including major genotypes ST433-t318, ST541-t034, ST5-t002, and ST9-t337. Staphylococcal enterotoxin and leukotoxin-encoding genes, alone or in combination, were detected in 68% of LR isolates. Isolates from different farms presented identical or different pulsed-field gel electrophoresis patterns. Collectively, toxigenic and LR S. aureus strains pose a crisis for public health. This study is the first to describe the mechanism of linezolid resistance in S. aureus isolated from food animal products in Korea.

We studied the presence of the mobile colistin resistance gene mcr-1 in Escherichia coli isolates recovered from fecal and urine samples of companion animals, that were collected from South Korea in 2018 and 2019. The mcr-1 gene was detected in one colistin-resistant E. coli isolated from a diarrheic dog. The isolate exhibited additional resistance to multiple antimicrobials, including fluoroquinolones and third-generation cephalosporins. The mcr-1 carrying isolate belonged to ST160. The pulsed-field gel electrophoresis pattern of our strain differed from those ST160 E. coli strains previously identified from chickens in Korea. The mcr-1 gene was identified in the IncI2 plasmid. It was also transferred to E. coli J53 recipient strain, with a conjugation efficiency of 2.8 × 10−4. Average nucleotide identity analysis demonstrated that the mcr-1-carrying plasmid in this study was closely related to those from patients in Korea. To the best of our knowledge, this is the first report of mcr-1 carrying E. coli from a companion animal in South Korea. Our findings support One Health approach is necessary to prevent the dissemination of this high-risk gene.

We examined the prevalence and molecular characteristics of mcr-3 carrying colistin-resistant Escherichia coli among cattle, pig, and chicken isolates in South Korea. Among a total of 185 colistin-resistant E. coli isolates determined in this study (47 from cattle, 90 from pigs, and 48 from chicken), PCR amplification detected mcr-3 genes in 17 isolates predominantly from diseased pigs. The mcr-3 genes were characterized as mcr-3.1 in 15 isolates and mcr-3.5 in 2 isolates. The mcr-3 gene was transferred to the E. coli J53 recipient strain from more than 50% of the mcr-3-carrying isolates. The mcr-3.1 and mcr-3.5 genes were identified predominantly in IncHI2 and IncP plasmids, respectively. Multi-locus sequence typing analysis revealed eight previously reported sequence types (ST), including ST1, ST10, and ST42. We identified isolates with similar pulsed-field gel electrophoresis patterns from diseased pigs in three farms. Besides, the isolates carried various virulence factors and demonstrated resistance to multiple antimicrobials, including β-lactams and quinolones. Further, the mcr-3.5 encodes three amino acid substitutions compared with mcr-3.1. To the best of our knowledge, this is the first report of pathogenic E. coli carrying mcr-3.5 in South Korea, which implies that mcr-3 variants may have already been widely spread in the pig industry.

Cellular senescence is induced in response to cellular stressors such as increased levels of reactive oxygen species. The chronic accumulation of senescent cells is currently recognized as a contributor to the pathologic processes of diverse degenerative diseases. Vitiligo is characterized by the disappearance of melanocytes driven by cellular stress within melanocytes and autoimmune processes. In this study, we examined p16INK4A positivity in the lesional and perilesional skin of 54 non-segmental vitiligo patients to explore cellular senescence in vitiligo. There were more p16INK4A-positive melanocytes in the perilesional vitiligo skin samples than in control samples. It was also found that p16INK4A immunoreactivity was not restricted to melanocytes but also existed in fibroblasts; the number of p16INK4A-positive fibroblasts was significantly increased in lesional skin compared to perilesional skin and normal controls. However, in the subgroup analysis of sun-exposed and non-exposed samples, this outcome was only found at sun-exposed sites, suggesting that fibroblast senescence is an epiphenomenon related to the loss of pigment in skin with vitiligo. In summary, exploring p16INK4A positivity in vitiligo revealed melanocyte senescence in perilesional skin, which may play a role in vitiligo pathogenesis.

We aimed to identify and characterize extended-spectrum β-lactamase (ESBL)-and/or plasmid-mediated AmpC β-lactamase (pAmpC)-producing Escherichia coli isolated from healthy broiler chickens slaughtered for human consumption in Korea. A total of 332 E. coli isolates were identified from 339 cloacal swabs in 2019. More than 90% of the isolates were resistant to multiple antimicrobials. ESBL/pAmpC-production was noted in 14% (46/332) of the isolates. Six of the CTX-M-β-lactamase-producing isolates were found to co-harbor at least one plasmid-mediated quinolone resistance gene. We observed the co-existence of blaCMY-2 and mcr-1 genes in the same isolate for the first time in Korea. Phylogenetic analysis demonstrated that the majority of blaCMY-2-carrying isolates belonged to subgroup D. Conjugation confirmed the transferability of blaCTX-M and blaCMY-2 genes, as well as non-β-lactam resistance traits from 60.9% (28/46) of the ESBL/pAmpC-producing isolates to a recipient E. coli J53. The ISECP, IS903, and orf477 elements were detected in the upstream or downstream regions. The blaCTX-M and blaCMY-2 genes mainly belonged to the IncI1, IncHI2, and/or IncFII plasmids. Additionally, the majority of ESBL/pAmpC-producing isolates exhibited heterogeneous PFGE profiles. This study showed that healthy chickens act as reservoirs of ESBL/pAmpC-producing E. coli that can potentially be transmitted to humans.

Recent progress in the understanding non-thermal plasma (NTP) properties prompted its application in the treatment of various diseases. However, therapeutic effect of NTP on keloid cells has not been reported previously. We sought to investigate the effect of NTP treatment on keloid by comparing cell migration and collagen production of keloid (KFs) and normal fibroblasts (NFs) and determined the regulatory pathways involved. We assessed NTP effects on cell migration in KFs and NFs by the wound healing assay and measured the expression of the epidermal growth factor receptor (EGFR), signal transducer and activator of transcription-3 (STAT3), and collagen by western blot. Expression of the transforming growth factor-β and Type I collagen following NTP treatment was determined by reverse transcription-polymerase chain reaction, immunofluorescence staining, and the Sircol collagen assay. NTP treatment increased cell migration and collagen production of NFs. However, it reduced these parameters in KFs. NTP reduced the expression of EGFR, STAT3, and Type I collagen in KFs but increased their levels in NFs. We revealed that NTP suppressed KF cell migration via down-regulation of EGFR and STAT3 and reduced collagen production via supressing transforming growth factor-β. Our data suggest that NTP may be a new therapeutic strategy for keloids.

Cortisol is a steroid hormone essential to the maintenance of homeostasis that is released in response to stress and low blood glucose concentration. Cortisol is converted from cortisone by 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1). It has been reported that too much cortisol or overexpression of HSD11B1 induces obesity and the insulin resistance that accompanies metabolic syndrome in rodent adipose tissue. In our previous study, HSD11B1-transgenic (TG) fibroblasts were established, and a porcine model was generated by SCNT using those fibroblasts. Hepatocytes overexpressing HSD11B1 were obtained from livers of this porcine model and cultured in vitro. However, the primary hepatocytes were found to have a short life span or low proliferation rate. To overcome these problems, the SV40 large T antigen was transduced into primary HSD11B1-TG hepatocytes, and those cells were immortalized. Immortalized HSD11B1-TG hepatocytes showed restored morphology, more rapid proliferation rate, and more expression of HSD11B1 than primary hepatocytes. As well, these cells kept the hepatic characteristics such as gluconeogenic response to cortisone and increased expression of hepatic makers. The immortalized HSD11B1-TG hepatocytes may be useful for studying traits and potential therapeutic drugs for treatment of metabolic disorders induced by overexpression of HSD11B1.

Natural killer (NK) cells are immune effector cells with outstanding features for adoptive immunotherapy. Immune effector cells with chimeric antigen receptors (CARs) are promising targeted therapeutic agents for various diseases. Because tumor cells exhibit heterogeneous antigen expression and lose cell surface antigen expression during malignant progression, many CARs fixed against only one antigen have limited efficacy and are associated with tumor relapse. To expand the utility of CAR-NK cells, we designed a split and universal cotinine-CAR (Cot-CAR) system, comprising a Cot-conjugator and NK92 cells (a-Cot-NK92 cells) engineered with a CAR containing an anti-Cotspecific single-chain variable fragment and intracellular signaling domain. The efficacy of the Cot-CAR system was assessed in vitro using a cytolysis assay against various tumor cells, and its single- or multiple-utility potential was demonstrated using an in vivo lung metastasis model by injecting A549-Red-Fluc cells. The a-Cot-NK92 cells could switch targets, logically respond to multiple antigens, and tune cytolytic activation through the alteration of conjugators without re-engineering. Therefore the universal Cot-CAR system is useful for enhancing specificity and diversity of antigens, combating relapse, and controlling cytolytic activity. In conclusion, this universal Cot-CAR system reveals that multiple availability and controllability can be generated with a single, integrated system. [ABSTRACT FROM AUTHOR]