Thymic development of gut-microbiota-specific T cells.

Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection1. Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen while limiting inflammatory anti-commensal responses1,2. Antigen-specific recognition of intestinal microorganisms by T cells has previously been described3,4. Although the local environment shapes the differentiation of effector cells3-5 it is unclear how microbiota-specific T cells are educated in the thymus. Here we show that intestinal colonization in early life leads to the trafficking of microbial antigens from the intestine to the thymus by intestinal dendritic cells, which then induce the expansion of microbiota-specific T cells. Once in the periphery, microbiota-specific T cells have pathogenic potential or can protect against related pathogens. In this way, the developing microbiota shapes and expands the thymic and peripheral T cell repertoire, allowing for enhanced recognition of intestinal microorganisms and pathogens.

Detection of Nα-terminally formylated native proteins by a pan-N-formyl methionine-specific antibody.

N-formyl methionine (fMet)-containing proteins are produced in bacteria, eukaryotic organelles mitochondria and plastids, and even in cytosol. However, Nα-terminally formylated proteins have been poorly characterized because of the lack of appropriate tools to detect fMet independently of downstream proximal sequences. Using a fMet-Gly-Ser-Gly-Cys peptide as an antigen, we generated a pan-fMet-specific rabbit polyclonal antibody called anti-fMet. The raised anti-fMet recognized universally and sequence context-independently Nt-formylated proteins in bacterial, yeast, and human cells as determined by a peptide spot array, dot blotting, and immunoblotting. We anticipate that the anti-fMet antibody will be broadly used to enable an understanding of the poorly explored functions and mechanisms of Nt-formylated proteins in various organisms.

Agendas on Nursing in South Korea Media: Natural Language Processing and Network Analysis of News From 2005 to 2022.

BACKGROUND: In recent years, Korean society has increasingly recognized the importance of nurses in the context of population aging and infectious disease control. However, nurses still face difficulties with regard to policy activities that are aimed at improving the nursing workforce structure and working environment. Media coverage plays an important role in public awareness of a particular issue and can be an important strategy in policy activities. OBJECTIVE: This study analyzed data from 18 years of news coverage on nursing-related issues. The focus of this study was to examine the drivers of the social, local, economic, and political agendas that were emphasized in the media by the analysis of main sources and their quotes. This analysis revealed which nursing media agendas were emphasized (eg, social aspects), neglected (eg, policy aspects), and negotiated. METHODS: Descriptive analysis, natural language processing, and semantic network analysis were applied to analyze data collected from 2005 to 2022. BigKinds were used for the collection of data, automatic multi-categorization of news, named entity recognition of news sources, and extraction and topic modeling of quotes. The main news sources were identified by conducting a 1-mode network analysis with SNAnalyzer. The main agendas of nursing-related news coverage were examined through the qualitative analysis of major sources' quotes by section. The common and individual interests of the top-ranked sources were analyzed through a 2-mode network analysis using UCINET. RESULTS: In total, 128,339 articles from 54 media outlets on nursing-related issues were analyzed. Descriptive analysis showed that nursing-related news was mainly covered in social (99,868/128,339, 77.82%) and local (48,056/128,339, 48.56%) sections, whereas it was rarely covered in economic (9439/128,339, 7.35%) and political (7301/128,339, 5.69%) sections. Furthermore, 445 sources that had made the top 20 list at least once by year and section were analyzed. Other than "nurse," the main sources for each section were "labor union," "local resident," "government," and "Moon Jae-in." "Nursing Bill" emerged as a common interest among nurses and doctors, although the topic did not garner considerable attention from the Ministry of Health and Welfare. Analyzing quotes showed that nurses were portrayed as heroes, laborers, survivors of abuse, and perpetrators. The economic section focused on employment of youth and women in nursing. In the political section, conflicts between nurses and doctors, which may have caused policy confusion, were highlighted. Policy formulation processes were not adequately reported. Media coverage of the enactment of nursing laws tended to relate to confrontations between political parties. CONCLUSIONS: The media plays a crucial role in highlighting various aspects of nursing practice. However, policy formulation processes to solve nursing issues were not adequately reported in South Korea. This study suggests that nurses should secure policy compliance by persuading the public to understand their professional perspectives.

N-Terminally arginylated ubiquitin is attached to histone H2A by RING1B E3 ligase in human cells.

Ubiquitin (Ub) is highly conserved in all eukaryotic organisms and begins at the N-terminus with Met and Gln. Our recent research demonstrates that N-terminally (Nt-) arginylated Ub can be produced in the yeast Saccharomyces cerevisiae. However, the existence of Nt-arginylated Ub in multicellular organisms remains unknown. Here we explore the mechanism for creating Nt-arginylated Ub using human embryonic kidney HEK293 cells that express various Nt-modified Ubs. We found that Gln-starting Q-Ub was converted into Glu-starting E-Ub by NTAQ1 Nt-deamidase and subsequently Nt-arginylated by ATE1 arginyltransferase in HEK293 cells. We also found that the resulting Arg-Glu-starting RE-Ub was mainly deposited on the Lys119 residue of histone H2A. Furthermore, RING1B E3 Ub ligase mediated the attachment of RE-Ub to H2A. These findings reveal a previously unknown type of histone ubiquitylation which greatly increases the combinatorial complexity of histone and ubiquitin codes.

AXL receptor tyrosine kinase inhibition improves the anti-tumor effects of CD8+ T cells by inducing CD103+ dendritic cell-mediated T cell priming.

AXL is a member of TAM receptor family and has been highlighted as a potential target for cancer treatment. Accumulating evidence has uncovered the critical role of the AXL signaling pathway in tumor growth, metastasis, and resistance against anti-cancer drugs, as well as its association with cancer immune escape. However, the function of AXL as a manipulator of the immune system in the tumor microenvironment (TME) remains unclear. Therefore, in this study, we investigated the impact of AXL on immune cells in the TME of a syngeneic tumor model using AXL knockout (AXL-/-) mice. Compared to AXL wild-type (AXL+/+) mice, tumor growth was significantly suppressed in AXL-/- mice, and an induced population of tumor-infiltrated CD8+ T cells and CD103+ dendritic cells (DCs) was observed. The change of CD8+ T cells and CD103+ DCs was also confirmed in tumor-draining lymph nodes (TdLN). In addition, the clonal expansion of OVA-specific CD8+ T cells was dominant in AXL-/- mice. Finally, anti-PD-1 treatment evidenced synergistic anti-cancer effects in AXL-/- mice. Overall, our data indicate that AXL signaling may inhibit the clonal expansion of tumor-specific CD8+ T cells through the regulation of the migration of CD8+ T cells and DCs in TME. Thus, AXL may be a powerful molecular target to improve anti-cancer effects through single or combined therapy with immune checkpoint inhibitors (ICI).

A Combination of Bio-Orthogonal Supramolecular Clicking and Proximity Chemical Tagging as a Supramolecular Tool for Discovery of Putative Proteins Associated with Laminopathic Disease.

Protein mutations alter protein-protein interactions that can lead to a number of illnesses. Mutations in lamin A (LMNA) have been reported to cause laminopathies. However, the proteins associated with the LMNA mutation have mostly remained unexplored. Herein, a new chemical tool for proximal proteomics is reported, developed by a combination of proximity chemical tagging and a bio-orthogonal supramolecular latching based on cucurbit[7]uril (CB[7])-based host-guest interactions. As this host-guest interaction acts as a noncovalent clickable motif that can be unclicked on-demand, this new chemical tool is exploited for reliable detection of the proximal proteins of LMNA and its mutant that causes laminopathic dilated cardiomyopathy (DCM). Most importantly, a comparison study reveals, for the first time, mutant-dependent alteration in LMNA proteomic environments, which allows to identify putative laminopathic DCM-linked proteins including FOXJ3 and CELF2. This study demonstrates the feasibility of this chemical tool for reliable proximal proteomics, and its immense potential as a new research platform for discovering biomarkers associated with protein mutation-linked diseases.

Maternal and newborn metabolomic changes associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations at delivery: an untargeted approach.

INTRODUCTION: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. METHOD: We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. RESULTS: Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. CONCLUSION: In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes.

Effect of the respiratory motion of pulmonary nodules on CT-guided percutaneous transthoracic needle biopsy.

BACKGROUND: Computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) is highly affected by respiratory motion; however, respiratory motion of target nodule during the PTNB and its effect on CT-guided lung biopsy have not been studied. PURPOSE: To investigate the effect of the respiratory motion of pulmonary nodules on CT-guided PTNB. MATERIAL AND METHODS: We retrospectively reviewed the procedural CT scans of 426 pulmonary nodules that underwent PTNB during quiet breathing. Maximal and average respiratory motions were measured using the difference of table position of the targeted nodule between multiple procedural scans. Diagnostic performance, complications, and technical factors of PTNB in nodules with large motion (maximal motion >1 cm) were compared with those in nodules with small motion (≤1 cm). RESULTS: The mean maximal and average respiratory motions between tidal volume breathing were 5.4 ± 4.4 and 2.7 ± 2.6 mm, respectively. Sensitivity and accuracy were 93.1% and 96.1% in nodules with large motion, compared with 94.7% and 95.9% in nodules with small motion, respectively. Respiratory targeting (P < 0.001), needle modulation (P < 0.001), motion artifact of target (P < 0.001), target disappearance from scans (P < 0.001), and number of performed CT scans (P < 0.001) were significantly higher in the large motion group, with no significant difference in radiation dose and complications between the groups. CONCLUSION: The respiratory motion of pulmonary nodules during CT-guided PTNB may cause technical difficulties but does not affect diagnostic performance nor complications associated with PTNB.

Anatomical Structures to Be Concerned With During Peripherally Inserted Central Catheter Procedures.

BACKGROUND: The central line has been frequently used for drug and nutrition supply and regular blood sampling of patients with chronic diseases. However, this procedure is performed in a highly sensitive area and has several potential complications. Therefore, peripherally inserted central catheters (PICC), which have various advantages, are being extensively used. Although the number of PICC procedures is increasing, the anatomy for safe procedures has not yet been properly established. Therefore, we studied basic anatomical information for safe procedures. METHODS: We used 20 fixed cadavers (40 arms) donated to the Korea University College of Medicine. The mean age was 76.75 years (range, 48-94 years). After dissection of each arm, the distribution pattern of the basilic vein and close structures was recorded, and some important parameters based on bony landmarks were measured. In addition, the number of vein branches (axillary region) and basilic vein diameter were also checked. RESULTS: The mean length from the insertion site to the right atrium was 38.39 ± 2.63 cm (left) and 34.66 ± 3.60 cm (right), and the basilic vein diameter was 4.93 ± 1.18 mm (left) and 4.08 ± 1.49 mm (right). The data showed significant differences between the left and right arms (P < 0.05). The mean distance from the basilic vein to brachial artery was 8.29 ± 2.78 mm in men and 7.81 ± 2.78 mm in women, while the distance to the ulnar nerve was 5.41 ± 1.67 mm in men and 5.52 ± 2.06 mm in women. CONCLUSION: According to these results, the right arm has a shorter distance from the insertion site to the right atrium, and the left arm has a wider vein diameter, which is advantageous for the procedure. In addition, the ulnar nerve and brachial artery were located close to or behind the insertion site. Therefore, special attention is required during the procedure to avoid damaging these important structures.

Osteoarthritis improvement effect of Chrysanthemum zawadskii var. latilobum extract in relation to genotype.

Objectives: To determine whether SNPs of osteoarthritis (OA)-related genes predict the effect of Chrysanthemum zawadskii var. latilobum (CZ) extract in OA patients with OA. Subjects/methods: To analyze correlations between CZ extract effects in humans and their genotypes, 121 Korean patients with OA were recruited. Patients ingested 600 mg/day of the CZ extract GCWB106 (one tablet daily), including 250-mg CZ, or placebo (one tablet daily) for 12 weeks. Twenty SNPs were genotyped in 11 genes associated with OA pathogenesis, including tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinases (MMPs), and 9 genes involved in OA-related dietary intervention. The Visual Analogue Scale (VAS) and Korean Western Ontario and McMaster Universities (K-WOMAC) were measured as indicators of GCWB106 effect. Statistical comparisons were performed using Kruskal-Wallis tests to identify associations between these scales and genotyped loci in patients with OA. Results: Three SNPs (PPARG rs3856806, MMP13 rs2252070, and ZIP2 rs2234632) were significantly associated with the degree of change in VAS pain score. Homozygous CC genotype carriers of rs3856806, G allele carriers (GA or GG) of rs2252070, and T allele carriers (GT or TT) of rs2234632 showed lower VAS score (i.e., less severe symptoms) in the GCWB106 group (n=53) than the placebo group (n=57) (p=0.026, p=0.009, and p=0.025, respectively). Gene-gene interaction effects on GCWB106-mediated pain relief were then examined, and it was found that the addition of each genotype resulted in a greater decrease in VAS pain score in the GCWB106 group (p=0.0024) but not the placebo group (p=0.7734). Conclusions: These novel predictive markers for the pain-relieving effects of GCWB106 may be used in the personalized treatment of patients with OA.

Serial Interval and Transmission Dynamics during SARS-CoV-2 Delta Variant Predominance, South Korea.

We estimated mean serial interval and superspreading potential for the Delta variant of severe acute respiratory syndrome coronavirus 2 in South Korea. Intervals were similar for the first (3.7 days) and second (3.5 days) study periods. Risk for superspreading events was also similar; 23% and 25% of cases, respectively, seeded 80% of transmissions.

Generation of genetically engineered mice for lung cancer with mutant EGFR.

Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown dramatic response and improvement in treating lung cancer with mutant EGFR, the emergence of drug resistance remains a major problem. In particular, some mutations including T790 M and C797S have been recognized as mechanisms of acquired resistance because they weaken binding affinity to drugs. To date, many attempts have been made to develop a new drug for overcoming acquired resistance to EGFR-TKIs, including secondary mutations. However, an appropriate animal model to evaluate in vivo efficacy during novel drug development remains lacking. In this study, we generated a novel transgenic mouse model that conditionally expresses human EGFRL858R/T790M/C797S and firefly luciferase using Cas9-mediated homology-independent targeted integration. Using a lung-specific Sftpc-CreERT2 mouse line, we induced expression of both the human EGFRL858R/T790M/C797S transgene and firefly luciferase in the lungs of adult mice. The expression of these genes and lung cancer occurrence was monitored using an in vivo imaging system and magnetic resonance imaging, respectively. Overall, our mouse model can be utilized to develop new drugs for overcoming C797S-mediated resistance to osimertinib; further, such knock-in systems for expressing oncogenes may be applied to study tumorigenesis and the development of other targeted agents.

Broadband high-performance terahertz polarizer based on a dense array of 5†nm gap slit antennas.

Critical factors for terahertz polarizers include broadband operation, high transmittance, and a good extinction ratio. In this paper, using a 5 nm-wide metallic slit array with a 200 nm periodicity as a wire grid polarizer, we achieved over 95% transmittance with an average extinction ratio of 40 dB, over the entire spectrum as defined by the terahertz time-domain spectroscopy (0.4 ∼ 2 THz). Theoretical calculations revealed that the slit array can show 100% transmission up to 5 THz, and wider bandwidths with a higher cutoff frequency can be achieved by reducing the slit periodicity. These results provide a novel approach for achieving a broadband THz polarizer and open a new path for seamless integration of the polarizers with nanophotonic applications.

Optimal placement for needle electromyography of the supinator muscle: Cadaveric studies.

INTRODUCTION/AIMS: The existing methods for needle electromyography are confusing as to which is the safest and most effective. Our aim was to identify the optimal and safest needle electromyographic insertion site in the supinator muscle. METHODS: We performed a two-step cadaveric dissection of the supinator muscle and related neurovascular structures. The study was performed using 18 upper limbs of 9 fresh adult cadavers (step 1) and 14 upper limbs of 7 fresh adult cadavers (step 2). In step 1, an imaginary line connecting the radial head (RH) and midpoint of the dorsal wrist (RW line) was drawn, and the distance from the RH to the point where the RW line and posterior interosseous nerve (PIN) intersect (L_CROSS) was measured on the RW line. In step 2, the needle was inserted 30 mm distal to the RH according to the results of step 1. After injection with India ink, dissection was performed to measure the distance between the needle insertion site and PIN (L_CROSS_Inj) on the RW line. RESULTS: The median L_CROSS was 51.4 (35.5-65.6) mm. Needle insertion spared the PIN in all cases during step 2, and the needle was inserted into the supinator muscle in all cases. The median L_CROSS_Inj was 27.4 (13.2-39.8) mm. DISCUSSION: A safe and accurate needle insertion site for the supinator muscle is approximately 30 to 40 mm distal to the RH along the RW line.

Effects of Depression on Changes in Cognitive Function in Older Adults: A Fixed-effects Model Analysis Using the Korean Longitudinal Study of Aging (KLoSA).

PURPOSE: This study identified the rate of change in cognitive function of community-based middle-aged and older adults and investigated the longitudinal effects of depression, health status, and health behavior by cognitive function group [normal, mild cognitive impairment (MCI), dementia] using data from the Korean Longitudinal Study of Aging. METHODS: This longitudinal panel analysis collected 21,425 data points from 4285 participants. Cognitive function change patterns in the groups were examined through descriptive analysis. A fixed-effects model was estimated using demographic factors, such as depression, health behavior, and disease states as independent variables. RESULTS: Compared with the baseline score of the mini-mental state examination (MMSE), the 8-year mean score decreased by 10.51, 8.6, and 1.21 for the dementia, MCI, and normal groups, respectively. The estimates for the normal group showed that an increase in the depression score significantly negatively impacted the MMSE score (B=-0.059, P <0.001). However, compared with those of the MCI group (B=-0.044, P >0.05), the estimates of the dementia group confirmed that depression significantly negatively affected cognitive function (B=-0.146, P <0.05). CONCLUSION: Each group showed different patterns of cognitive decline. An annual follow-up cognitive impairment screening to investigate changes in MMSE score in community-based older individuals can enable early detection of dementia.

Is Free Breathing Possible During Computed Tomography-Guided Percutaneous Transthoracic Lung Biopsy? The Clinical Experience in 585 Cases.

OBJECTIVE: The aim of the study was to retrospectively evaluate the safety and accuracy of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) of lung lesions during quiet breathing. METHODS: We investigated the diagnostic performance and complication rate of 585 procedures in 563 patients (357 men; mean age, 67.7 years), who underwent CT-guided PTNBs during quiet breathing, aided by a respiratory targeting technique from May 2017 to July 2019. Differences between the cases with and without respiratory targeting were analyzed. Logistic regression analyses were performed to examine the development of pneumothorax and hemoptysis. RESULTS: Percutaneous transthoracic needle biopsy samples were successfully obtained in 574 of 585 procedures (98.1%). Final diagnoses included: 410 malignant cases, 119 benign cases, and 45 indeterminate cases. The sensitivity, specificity, and accuracy of diagnosis were 94.4%, 100%, and 95.7%, respectively. Use of respiratory targeting was associated with younger age (P = 0.004), smaller lesion size (P < 0.001), peripheral location (P = 0.003), shorter distance from the diaphragm (P < 0.001), lower lobe location (P < 0.001), prone position (P = 0.004), and visible motion artifact (P < 0.001). Pneumothorax and hemoptysis rates were 22.9% and 7.9%, respectively. Upon multivariate analysis, emphysema (P = 0.002) was the only independent risk factor for pneumothorax, whereas distance from the pleura greater than 2 cm (P < 0.001), tissue sampling 3 times or more (P = 0.003), and a less experienced operator (P < 0.001) were risk factors for hemoptysis. CONCLUSIONS: Computed tomography-guided PTNB during quiet breathing with respiratory targeting yielded high diagnostic performance with a slightly higher rate of complications. Free-breathing PTNB can be applied in clinical practice, based on lesion location and risk factors for complications.

Complications of Nasopharyngeal Swabs and Safe Procedures for COVID-19 Testing Based on Anatomical Knowledge.

Nasopharyngeal swabs have been widely to prevent the spread of coronavirus disease 2019 (COVID-19). Nasopharyngeal COVID-19 testing is a generally safe and well-tolerated procedure, but numerous complications have been reported in the media. Therefore, the present study aimed to review and document adverse events and suggest procedural references to minimize preventable but often underestimated risks. A total of 27 articles were selected for the review of 842 related documents in PubMed, Embase, and KoreaMed. The complications related to nasopharyngeal COVID-19 testing were reported to be rarely happened, ranging from 0.0012 to 0.026%. Frequently documented adverse events were retained swabs, epistaxis, and cerebrospinal fluid leakage, often associated with high-risk factors, including severe septal deviations, pre-existing skull base defects, and previous sinus or transsphenoidal pituitary surgery. Appropriate techniques based on sufficient anatomical knowledge are mandatory for clinicians to perform nasopharyngeal COVID-19 testing. The nasal floor can be predicted by the line between the nostril and external ear canal. For safe testing, the angle of swab insertion in the nasal passage should remain within 30° of the nasal floor. The swab was gently inserted along the nasal septum just above the nasal floor to the nasopharynx and remained on the nasopharynx for several seconds before removal. Forceful insertion should be attempted, and alternative examinations should be considered, especially in vulnerable patients. In conclusion, patients and clinicians should be aware of rare but possible complications and associated high-risk factors. The suggested procedural pearls enable more comfortable and safe nasopharyngeal COVID-19 testing for both clinicians and patients.

Reconstruction of Extensive Oromandibular Defect With Simultaneous Dual Free Flap Transfer.

ABSTRACT: Complex oromandibular defects are usually too extensive or complex to be reconstructed with a single free flap. In this situation, dual free flaps can provide an adequate amount of tissues and a three-dimensional structure for large composite defects.In our institution, a total of 6 patients underwent immediate dual free-flap reconstruction between December 2013 and February 2020. In all patients, oromandibular defects were reconstructed with a combination of a fibula free flap and a vertical rectus abdominis myocutaneous, anterolateral thigh, or radial forearm free flap. All 6 patients showed tolerable flap status without any major complications, and could transit a diet from a dysphagia diet to a general diet on the final visit. Dual free flaps can be considered an optimal reconstructive option with favorable functional and aesthetic outcomes for complex oromandibular defects involving the bone, oral lining, external skin, or soft tissue.

Male breast cancer presenting in accessory axillary breast.

We present a rare case of male axillary accessory breast cancer, which is extremely rare and is indistinguishable from lymphadenopathy and other malignancies, such as lymphoma and skin-derived tumors. Clinicians should consider accessory breast cancer in the differential diagnosis even in men, particularly in those who present with superficially located tumors with adjacent accessory breast tissue.

Topology-Changing Broadband Metamaterials Enabled by Closable Nanotrenches.

One of the most straightforward methods to actively control optical functionalities of metamaterials is to apply mechanical strain deforming the geometries. These deformations, however, leave symmetries and topologies largely intact, limiting the multifunctional horizon. Here, we present topology manipulation of metamaterials fabricated on flexible substrates by mechanically closing/opening embedded nanotrenches of various geometries. When an inner bending is applied on the substrate, the nanotrench closes and the accompanying topological change results in abrupt switching of metamaterial functionalities such as resonance, chirality, and polarization selectivity. Closable nanotrenches can be embedded in metamaterials of broadband spectrum, ranging from visible to microwave. The 99.9% extinction performance is robust, enduring more than a thousand bending cycles. Our work provides a wafer-scale platform for active quantum plasmonics and photonic application of subnanometer phenomena.