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The Hedgehog (Hh) signaling pathway is involved in T cell differentiation and development and plays a major regulatory part in different stages of T cell development. A previous study by us suggested that prenatal exposure to staphylococcal enterotoxin B (SEB) changed the percentages of T cell subpopulation in the offspring thymus. However, it is unclear whether prenatal SEB exposure impacts the Hh signaling pathway in thymic T cells. In the present study, pregnant rats at gestational day 16 were intravenously injected once with 15 µg SEB, and the thymi of both neonatal and adult offspring rats were aseptically acquired to scrutinize the effects of SEB on the Hh signaling pathway. It firstly found that prenatal SEB exposure clearly caused the increased expression of Shh and Dhh ligands of the Hh signaling pathway in thymus tissue of both neonatal and adult offspring rats, but significantly decreased the expression levels of membrane receptors of Ptch1 and Smo, transcription factor Gli1, as well as target genes of CyclinD1, C-myc, and N-myc in Hh signaling pathway of thymic T cells. These data suggest that prenatal SEB exposure inhibits the Hh signaling pathway in thymic T lymphocytes of the neonatal offspring, and this effect can be maintained in adult offspring via the imprinting effect.
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Enterotoxinas , Proteínas Hedgehog , Transdução de Sinais , Linfócitos T , Timo , Animais , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Feminino , Gravidez , Ratos , Timo/metabolismo , Timo/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Receptor Patched-1/metabolismo , Receptor Patched-1/genética , Receptor Smoothened/metabolismo , Receptor Smoothened/genética , Efeitos Tardios da Exposição Pré-Natal/imunologia , Diferenciação Celular/efeitos dos fármacos , Ratos Sprague-Dawley , MasculinoRESUMO
BACKGROUND: The purpose of this study was to review echocardiography-based diagnosis of persistent fifth aortic arch (PFAA) in children. METHODS: From January 2015 to December 2022, we retrospectively analyzed the echocardiographic findings and the relevant clinical data during follow-up of patients with PFAA who were treated in the Third Affiliated Hospital of Zhengzhou University. The diagnosis was confirmed by computed tomography angiography or surgery. RESULTS: Seven PFAA cases included two Weinberg type A and five Weinberg type B. The anatomical details of PFAA were assessed using a combination of the long-axis view of the left ventricular outflow tract (from the left high parasternal window) and the long-axis view of the aortic arch (from the suprasternal window). In Weinberg type A, the distal fifth and fourth aortic arches were connected to the descending aorta, which was associated with aortic coarctation. In Weinberg type B, the upper arch of the fourth aorta was interrupted, and only the lower arch of the fifth aorta was connected to the descending aorta. Surgical repair of PFAA was indicated in five patients with blood flow disruption, among which four had good postoperative results and one refused surgery. Two patients with unobstructed PFAA blood flow required follow-up rather than surgery. CONCLUSIONS: It is feasible to diagnose PFAA by echocardiography. Combined application of the high parasternal left ventricular outflow tract view and the suprasternal aortic arch view can improve timely detection of different types of PFAA in children.
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Aorta Torácica , Angiografia por Tomografia Computadorizada , Valor Preditivo dos Testes , Humanos , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/anormalidades , Aorta Torácica/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Lactente , Pré-Escolar , Aortografia , Criança , China , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/cirurgia , Resultado do Tratamento , Fatores Etários , Reprodutibilidade dos Testes , EcocardiografiaRESUMO
CO2-to-high value-added chemicals via a photocatalytic route is of interest but strangled by the low efficiency. Herein, a novel Fe-TiO2-x/TiO2 S-scheme homojunction was designed and constructed by using a facile surface modification approach whereby oxygen vacancy (OV) and Fe introducing on the TiO2 nanorod surface. The as-synthesized Fe-TiO2-x/TiO2 S-scheme homojunction exhibits positive properties on promoting photocatalytic CO2 reduction: i) the nanorod structure provides numerous active sites and a radical charge transfer path; ii) the doped Fe and OV not only synergistically enhance light utilization but also promote CO2 adsorption; iii) the Fe-TiO2-x/TiO2 S-scheme homojunction benefits photoexcited charge separation and retains stronger redox capacity. Thanks to those good characters, the Fe-TiO2-x/TiO2 homojunction exhibits superior CO2 reduction performances with optimized CO/CH4 generation rates of 122/22 µmol g-1h-1 which exceed those of pure TiO2 by more than 9.4/7.3 folds and most currently reported catalytic systems. This manuscript develops a facile and universal approach to synthesize well-defined homojunction and may inspire the construction of other more high-efficiency photocatalysts toward CO2 reduction and beyond.
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This retrospective cross-sectional study reviewed adult patients with operated cleft lip and/or palate (CL/P) and normal control, and performed comprehensive craniofacial and nasal morphological analyses based on lateral cephalometric radiographs. Pearson or Spearman correlation coefficient assessed intraclass correlation. Seven hundred fifty-seven operated patients with CL/P, and 165 noncleft normal controls were enrolled. Among the normal and CL/P groups, S-N-A angle registered positive correlations with nasal base prominence (S-N'-Sn, degrees). Upper facial height (N-ANS, mm) had positive correlations with nasal dorsum length (N'-Prn, mm) and nasal bone length (N-Na, mm). Although in patients with bilateral cleft lip and palate, there were moderate negative correlations ( r =-0.541, P <0.05) with soft tissue facial profile angle (FH-N'Pog', degree) and nasolabial angle (Cm-Sn-ULA, degree). Correlation exists between the morphology of jaw bones and external nose among patients with CL/P. Maxillary sagittal insufficiency is associated with concave nasal profile, and maxilla height is associated with nasal length.
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Cefalometria , Fenda Labial , Fissura Palatina , Nariz , Humanos , Fenda Labial/patologia , Fenda Labial/diagnóstico por imagem , Fenda Labial/cirurgia , Fissura Palatina/patologia , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Estudos Transversais , Adulto , Nariz/diagnóstico por imagem , Nariz/anatomia & histologia , Nariz/patologia , Estudos de Casos e Controles , Adolescente , Maxila/diagnóstico por imagem , Maxila/patologiaRESUMO
BACKGROUND: Posterior pharyngeal flap (PPF) is effective in managing velopharyngeal insufficiency (VPI) but is of airway obstruction risk. This study compared the effectiveness and complications of two PPF revision procedures and screened potential prognostic factors to postoperative hypernasality and persistent obstruction. METHODS: Patients who received flap division (FD) or port enlargement (PE) for airway obstruction following PPF were reviewed. Ventilation status was assessed using the nasal obstruction symptom evaluation (NOSE) scale, and velopharyngeal closure was assessed using subjective speech evaluation and nasopharyngoscopy. The effectiveness of ventilation relief and complication rate (hypernasality and persistent obstruction) of the two techniques were compared. A comprehensive panel of factors, including age, velopharyngeal mobility, obstruction laterality, body mass index, jaw relationship, and adenoid hypertrophy, were evaluated for correlation with complications. RESULTS: 79 patients were enrolled, with 51 receiving FD and 28 PE. Both techniques significantly improved ventilation dysfunction and hyponasality. Mild hypernasality occurred among 10 cases in the FD group and 3 in the PE group. Age at surgery was significantly associated with persistent obstruction after PPF revision. The occurrence of persistent obstruction was significantly higher among patients below 12 years than those above. Obstruction laterality was suggested in significant correlation with hypernasality post-PPF revision. Among patients with unilateral port obstruction, the occurrence of hypernasality after FD was significantly higher than after PE. CONCLUSION: Both flap division and port enlargement are effective revision procedures to relieve airway obstruction after PPF. Patients below 12 years are more likely to experience persistent ventilation problem after PPF revision.
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Single-nucleotide polymorphism (SNP) is one of the core mechanisms that respond to antibiotic resistance of Escherichia coli (E. coli), which is a major issue in environmental pollution. A specific type of SNPs, synonymous SNPs, have been generally considered as the "silent" SNPs since they do not change the encoded amino acid. However, the impact of synonymous SNPs on mRNA splicing, nucleo-cytoplasmic export, stability, and translation was gradually discovered in the last decades. Figuring out the mechanism of synonymous SNPs in regulating antibiotic resistance is critical to improve antimicrobial therapy strategies in clinics and biological treatment strategies of antibiotic-resistant E. coli-polluted materials. With our newly designed antibiotic resistant SNPs prediction algorithm, Multilocus Sequence Type based Identification for Phenotype-single nucleotide polymorphism Analysis (MIPHA), and in vivo validation, we identified 2 important synonymous SNPs 522 G>A and 972 C>T, located at hisD gene, which was previously predicted as a fluoroquinolone resistance-related gene without a detailed mechanism in the E. coli samples with environmental backgrounds. We first discovered that hisD causes gyrA mutation via the upregulation of sbmC and its downstream gene umuD. Moreover, those 2 synonymous SNPs of hisD cause its own translational slowdown and further reduce the expression levels of sbmC and its downstream gene umuD, making the fluoroquinolone resistance determining region of gyrA remains unmutated, ultimately causing the bacteria to lose their ability to resist drugs. This study provided valuable insight into the role of synonymous SNPs in mediating antibiotic resistance of bacteria and a new perspective for the treatment of environmental pollution caused by drug-resistant bacteria.
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Escherichia coli , Fluoroquinolonas , Fluoroquinolonas/farmacologia , Escherichia coli/genética , Polimorfismo de Nucleotídeo Único , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologiaRESUMO
The phenotype-first approach (PFA) and data-driven approach (DDA) have both greatly facilitated anthropological studies and the mapping of trait-associated genes. However, the pros and cons of the two approaches are poorly understood. Here, we systematically evaluated the two approaches and analyzed 14,838 facial traits in 2,379 Han Chinese individuals. Interestingly, the PFA explained more facial variation than the DDA in the top 100 and 1,000 except in the top 10 phenotypes. Accordingly, the ratio of heterogeneous traits extracted from the PFA was much greater, while more homogenous traits were found using the DDA for different sex, age, and BMI groups. Notably, our results demonstrated that the sex factor accounted for 30% of phenotypic variation in all traits extracted. Furthermore, we linked DDA phenotypes to PFA phenotypes with explicit biological explanations. These findings provide new insights into the analysis of multidimensional phenotypes and expand the understanding of phenotyping approaches.
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Liposomes as carriers for CRISPR/Cas9 complexes represent an attractive approach for cardiovascular gene therapy. A critical barrier to this approach remains the efficient delivery of CRISPR-based genetic materials into cardiomyocytes. Echogenic liposomes (ELIP) containing a fluorescein isothiocyanate-labeled decoy oligodeoxynucleotide against nuclear factor kappa B (ELIP-NF-κB-FITC) were used both in vitro on mouse neonatal ventricular myocytes and in vivo on rat hearts to assess gene delivery efficacy with or without ultrasound. In vitro analysis was then repeated with ELIP containing Cas9-sg-IL1RL1 (interleukin 1 receptor-like 1) RNA to determine the efficiency of gene knockdown. ELIP-NF-κB-FITC without ultrasound showed limited gene delivery in vitro and in vivo, but ultrasound combined with ELIP notably improved penetration into heart cells and tissues. When ELIP was used to deliver Cas9-sg-IL1RL1 RNA, gene editing was successful and enhanced by ultrasound. This innovative approach shows promise for heart disease gene therapy using CRISPR technology.
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Radiological heart damage (RIHD) is damage caused by unavoidable irradiation of the heart during chest radiotherapy, with a long latency period and a progressively increasing proportion of delayed cardiac damage due to conventional doses of chest radiotherapy. There is a risk of inducing diseases such as acute/chronic pericarditis, myocarditis, delayed myocardial fibrosis and damage to the cardiac conduction system in humans, which can lead to myocardial infarction or even death in severe cases. This paper details the pathogenesis of RIHD and gives potential targets for treatment at the molecular and cellular level, avoiding the drawbacks of high invasiveness and immune rejection due to drug therapy, medical device implantation and heart transplantation. Injectable hydrogel therapy has emerged as a minimally invasive tissue engineering therapy to provide necessary mechanical support to the infarcted myocardium and to act as a carrier for various bioactive factors and cells to improve the cellular microenvironment in the infarcted area and induce myocardial tissue regeneration. Therefore, this paper combines bioactive factors and cellular therapeutic mechanisms with injectable hydrogels, presents recent advances in the treatment of cardiac injury after RIHD with different injectable gels, and summarizes the therapeutic potential of various types of injectable hydrogels as a potential solution.
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Hidrogéis , Injeções , Hidrogéis/química , Humanos , Animais , Lesões por Radiação/terapia , Lesões por Radiação/etiologia , Cardiopatias/terapia , Cardiopatias/etiologia , Engenharia Tecidual , Infarto do Miocárdio/terapiaRESUMO
Background/purpose: Root canal filling is a necessary skill for dental students and an important aspect of endodontic education. This study aimed to evaluate the effect of students' clinical experiences on isthmus filling using different techniques and sealers. Materials and methods: One hundred eight three-dimensional-printed resin replicas of isthmus were divided into six groups and either continuous wave of condensation (CWC) or single-cone obturation (SC) was performed. One of three sealers (AH Plus Jet®, GuttaFlow2, iRoot SP) was used together with a size-fitted gutta-percha master cone. All the obturations were completed by students with three different levels of clinical experience including senior postgraduate students (SPS), junior postgraduate students (JPS), and undergraduate students (US). The percentages of filled areas (PFA) at 2, 4, 6, and 8 mm from the apex were analyzed using a light microscope. Data were analyzed using the Mann-Whitney U test or Kruskal-Wallis 1-way ANOVA with Dunn's tests (α = 0.05). Results: The CWC group exhibited a higher PFA than the SC group (P < 0.05). The PFA was higher in the SPS group than in the JPS group or the US group with CWC (P < 0.05). The three clinical experience groups showed similar PFAs with SC (P > 0.05); however, when using SC with iRoot SP, the PFA was higher than with either of the other two sealers (P < 0.05). Conclusion: CWC was found to be technique-sensitive and required clinical training. With SC, clinical experience did not improve the quality of isthmus filling without additional training. CWC was superior to SC for type IV isthmuses. When using SC, better filling quality was obtained with a bioceramic sealer.
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An unprecedented strategy for preparing a series of sulfur ylides through electro-oxidative quinylation of sulfides in batch and continuous flow has been developed. Good to excellent yields were obtained with excellent functional group compatibility and good concentration tolerance under exogenous oxidant- and transition metal-free conditions. Advantageously, this electrosynthesis methodology was scalable with higher daily production and steady production was achieved attributing to the use of micro-flow cells.
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Currently, severe membrane fouling and inefficient nitrogen removal were two main issues that hindered the sustainable operation and further application of membrane bioreactor (MBR). This study aimed to simultaneously alleviate membrane fouling and improve nitrogen removal by applying high sludge concentration in MBR. Results showed that high sludge concentration (12000 mg/L) enhanced total nitrogen removal efficiency (78 %) and reduced transmembrane pressure development rate. Microbial community analysis revealed that high sludge concentration enriched functional bacteria associated with nitrogen removal, increased filamentous bacteria fraction in bio-cake and inhibited Thiothrix overgrowth in bulk sludge. From molecular level, the key genes involved in nitrogen metabolism, electron donor/adenosine triphosphate production and amino acid degradation were up-regulated under high sludge concentration. Overall, high sludge concentration improved microbial assembly and functional gene abundance, which not only enhanced nitrogen removal but also alleviated membrane fouling. This study provided an effective strategy for sustainable operation of MBR.
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Incrustação Biológica , Esgotos , Esgotos/microbiologia , Nitrificação , Incrustação Biológica/prevenção & controle , Desnitrificação , Metagenoma , Reatores Biológicos/microbiologia , Nitrogênio , Membranas ArtificiaisRESUMO
Bladder cancer (BCa), which usually occurs in bladder epithelial cells and is the fifth most common type of cancer in the world. he recurrence rate within 5 years after surgery is 0.8-45% of patients with early bladder cancer. Therefore, finding appropriate drug therapy for patients with bladder cancer can provide a reference for clinical treatment and play an important role in improving the prognosis of patients. In this study, CCK8 assay result showed that the inhibition of bladder cancer cell activity by Curdione and GEM increased with time and dose. Subsequently, CCK8, clone formation assay and Transwell result showed Curdione enhances GEM inhibition of bladder cancer cell activity, clonal formation and migration, these combine therapeutic schedule also could inhibited growth of in vivo xenograft tumors. The comprehensive database showed that CA2 is a potential target genes of Curdione, and Knockdown CA2 enhances GEM induced inhibition of cell proliferation and migration. Based on these advantages, Curdione may be a new type of action drug or adjunct for the treatment of bladder cancer.
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An electrosynthesis of spiro-indolenines in batch and continuous flow was achieved through dearomative arylation of indoles with good functional group compatibility. User-friendly undivided cells were used under catalyst- and oxidant-free conditions. Moreover, the use of a flow electrolysis cell gave high daily productivity and excellent scale-up potential under less supporting electrolyte and higher substrate concentration conditions.
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Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in vivo embolic middle cerebral artery occlusion (eMCAO) rat model. The treatment groups received intravenous administration of Xe-liposomes (20 mg/kg) at 2 h post-stroke onset, followed by the administration of rtPA (10 mg/kg) at either 2 or 4 h after the onset. Three days after the stroke, behavioral tests were conducted, and brain sections were collected for triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was determined as normalized infarct volume (%). Both in vitro and in vivo clot lysis experiments demonstrated that Xe-liposomes in combination with rtPA resulted in effective clot lysis comparable to the treatment with free rtPA alone. Animals treated with Xe-liposomes in combination with rtPA showed reduced TUNEL-positive cells and demonstrated improved neurological recovery. Importantly, Xe-liposomes in combination with late rtPA treatment reduced rtPA-induced hemorrhage, attributing to the reduction of MMP9 immunoreactivity. This study demonstrates that the combined therapy of Xe-liposomes and rtPA provides enhanced therapeutic efficacy, leading to decreased neuronal cell death and a potential to mitigate hemorrhagic side effects associated with late rtPA treatment.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Ratos , Ativador de Plasminogênio Tecidual/farmacologia , Ativador de Plasminogênio Tecidual/uso terapêutico , Lipossomos , Acidente Vascular Cerebral/tratamento farmacológico , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Infarto , Terapia TrombolíticaRESUMO
The CRISPR-based genome editing technology, known as clustered regularly interspaced short palindromic repeats (CRISPR), has sparked renewed interest in gene therapy. This interest is accompanied by the development of single-guide RNAs (sgRNAs), which enable the introduction of desired genetic modifications at the targeted site when used alongside the CRISPR components. However, the efficient delivery of CRISPR/Cas remains a challenge. Successful gene editing relies on the development of a delivery strategy that can effectively deliver the CRISPR cargo to the target site. To overcome this obstacle, researchers have extensively explored non-viral, viral, and physical methods for targeted delivery of CRISPR/Cas9 and a guide RNA (gRNA) into cells and tissues. Among those methods, liposomes offer a promising approach to enhance the delivery of CRISPR/Cas and gRNA. Liposomes facilitate endosomal escape and leverage various stimuli such as light, pH, ultrasound, and environmental cues to provide both spatial and temporal control of cargo release. Thus, the combination of the CRISPR-based system with liposome delivery technology enables precise and efficient genetic modifications in cells and tissues. This approach has numerous applications in basic research, biotechnology, and therapeutic interventions. For instance, it can be employed to correct genetic mutations associated with inherited diseases and other disorders or to modify immune cells to enhance their disease-fighting capabilities. In summary, liposome-based CRISPR genome editing provides a valuable tool for achieving precise and efficient genetic modifications. This review discusses future directions and opportunities to further advance this rapidly evolving field.
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Edição de Genes , Lipossomos , RNA Guia de Sistemas CRISPR-Cas , Biotecnologia , Sinais (Psicologia)RESUMO
Marginal velopharyngeal inadequacy (MVPI) is a particular status of velopharyngeal closure after cleft palate repair. The physiological and phonological characteristics of patients with MVPI are significantly different from those with typical velopharyngeal insufficiency. The pathological mechanisms and diagnostic criteria of MVPI are still controversial, and there is limited evidence to guide the selection of surgical and non- surgical management options and a lack of recognized standards for treatment protocols. Based on a systematic study of the relevant literatures, this review identifies specific problems that are currently under-recognized in the diagnosis and treatment of MVPI and provides guidelines for further exploration of standardized and reasonable intervention protocols for MVPI.
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Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/ß-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/ß-catenin signaling via high expression of LGR6 promoted by HnRNPK.
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Cementogênese , RNA Longo não Codificante , Camundongos , Animais , Via de Sinalização Wnt , beta Catenina/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , RNA Longo não Codificante/genética , Hormônio Paratireóideo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Cancer stem cells (CSCs) are a small proportion of the cells that exist in cancer tissues. They are considered to be the culprit of tumor genesis, development, drug resistance, metastasis and recurrence because of their self-renewal, proliferation, and differentiation potential. The elimination of CSCs is thus the key to cure cancer, and targeting CSCs provides a new method for tumor treatment. Due to the advantages of controlled sustained release, targeting and high biocompatibility, a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs. This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs. Furthermore, we identify the problems and future research directions of nanotechnology in CSC therapy. We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.
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Cyclic peptides have been excellent source of drug leads. With the advances in discovery platforms, the pharmaceutical industry has a growing interest in cyclic peptides and has pushed several into clinical trials. However, structural complexity of cyclic peptides brings extreme challenges for structure elucidation efforts. Isotopic fine structure analysis, Nuclear magnetic resonance (NMR), and detailed tandem mass spectrometry rapidly provided peptide sequence for streptnatamide A, a cyclic peptide isolated from a marine-derived Streptomyces sp. Marfey's analysis determined the stereochemistry of all amino acids, enabling the unambiguous structure determination of this compound. A non-ribosomal peptide synthetase biosynthetic gene cluster (stp) was tentatively identified and annotated for streptnatamide A based on the in silico analysis of whole genome sequencing data. These analytical tools will be powerful tools to overcome the challenges for cyclic peptide structure elucidation and accelerate the development of bioactive cyclic peptides.