Facile Synthesis and First Antifungal Exploration of Tetracyclic Meroterpenoids: (+)-Aureol, (-)-Pelorol, and Its Analogs.

As an important bioactive molecular backbone, drimane meroterpenoids have drawn a great deal of attention from both pharmacologists and chemists. Inspired by the prevalidated success of conformational restriction in the discovery of novel pharmaceutical leads, two distinct tetracyclic drimane meroterpenoids, (-)-pelorol and (+)-aureol, were synthesized from the inexpensive starting material (-)-sclareol through 10 and 8 steps with 5.6% and 5.4% overall yield, respectively. The mild conditions, operational facility, and scalability enabled the expedient synthesis and biological exploration of not only natural products themselves but also their mimics. The first agrochemical exploration showed (-)-pelorol and (+)-aureol possessed good antifungal activity against Rhizoctonia solani, with EC50 values of 7.7 and 6.9 µM, respectively. This revealed that tetracyclic drimane meroterpenoids are valuable models for antifungal lead discovery.

Design and Discovery of α-Oximido-arylacetamides as Novel Antifungal Leads.

The discovery of novel and easily accessible antifungal compounds is an imperative issue in agrochemical innovation. Our continuing research with the o-aminophenyloxazoline (NHPhOx) scaffold demonstrated the viability of introducing phenylacetamides for identifying novel antifungal leads. An antifungal function-oriented molecular evaluation was conducted for the previously identified lead R-LE008. Fine-tuning of the α-position and scaffold hopping of acid segment and NHPhOx enables α-oximido-arylacetamide as a novel antifungal model. The concomitant function-oriented diversification produces a panel of antifungal leads CN19, CN21b, CN28, and CN31 against Sclerotinia sclerotiorum and Botrytis cinerea. The crucial and multidimensional effect of the configuration of the acquired amides on the antifungal performance is demonstrated specifically by the separable CN21 isomers. The Z-isomer (CN21b), with an EC50 value of 0.97 µM against B. cinerea, is significantly more potent than its E-isomer (CN21a) and the positive control boscalid. More importantly, compound CN21b can efficiently inhibit resistant B. cinerea strains. CN21b demonstrates a better in vivo preventative effect (82.1%) than those of CN21a (48.1%) and boscalid (55.1%) at 100 µM. CN21b showed a distinct binding model from those of the boscalid and CN21a in the molecular docking simulation. A further morphological investigation by scanning electron microscopy revealed the different mycelia shrinkage of B. cinerea treated by CN21 isomers. The easy accessibility and cost-effectiveness demonstrated the practical potential of α-oximido-phenylacetamide containing NHPhOx as a new model for agrochemical innovation.

Antifungal Function Oriented Scaffold Hopping for the Discovery of Oxazolyl-oxazoline as a Novel Model against Fusarium graminearum.

Discovery of novel structural models is extremely important in agrochemical innovation. Scaffold hopping was conducted, and 16 kinds of novel models were synthesized and biologically evaluated. Oxazolyl-oxazoline 25 showed a promising in vitro potential against Fusarium graminearum with EC50 value of 18.25 µM, which was 2.4 times more potent than that of carbendazim (EC50 = 43.06 µM). The antifungal structure-activity relationship (SAR) revealed that compound 25am had the most promising antifungal activity against F. graminearum, with an EC50 value of 13.46 µM, which was 3.2 more potent than that of carbendazim. Different from carbendazim, the candidate 25am could form five hydrogen bonds with the amino acid residues in ß-tubulin in the molecular docking and could effectively inhibit the carbendazim-resistant F. graminearum strain. Scanning electron microscopy (SEM) revealed that compound 25am induced the mycelia of F. graminearum slight collapse. This work suggests that compound 25am should be prioritized for further evaluation for new antifungal agents.

Research on Optical Fiber Ring Resonator Q Value and Coupling Efficiency Optimization.

The coupling efficiency of the fiber ring resonator has an important influence on the scale factor of the resonant fiber gyroscope. In order to improve the scale factor of the gyroscope, the coupling efficiency of the fiber ring resonator and its influential factors on the scale factor of the gyroscope are analyzed and tested. The results show that the coupling efficiency is affected by both the splitting ratio of the coupler and the loss in the cavity. When the coupling efficiency approaches 0.75 at the under-coupling state, the scaling factor of the gyroscope is the highest. This provides a theoretical reference and an experimental basis for the enhancement of the scaling factor of the resonant fiber gyroscope with the fiber ring resonator as the sensitive unit, providing options for multiple applications such as sea, land, sky and space.

Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates.

The discovery of novel and easily available leads provides a convincing solution to agrochemical innovation. A bioassay-guided scaffold subtraction of the previous "Chem-Bio Model" isoquinoline-3-oxazoline MIQOX was conducted for identifying the easily available isoquinoline-3-hydrazide as a novel antifungal scaffold. The special and practical potential of this model was demonstrated by a phenotypic antifungal bioassay, molecular docking, and cross-resistance evaluation. A panel of antifungal leads (LW2, LW3, and LW11) was acquired, showing much better antifungal performance than the positive controls. Specifically, compound LW3 exhibited a broad antifungal spectrum holding EC50 values as low as 0.54, 0.09, 1.52, and 2.65 mg/L against B. cinerea, R. solani, S. sclerotiorum , and F. graminearum, respectively. It demonstrated a curative efficacy better than that of boscalid in controlling the plant disease caused by B. cinerea. The candidate LW3 did not show cross-resistance to the extensively used succinate dehydrogenase inhibitor (SDHI) fungicides and can efficiently inhibit resistant B. cinerea strains. The molecular docking of compound LW3 is quite different from that of the positive controls boscalid and fluopyram. This progress highlights the practicality of isoquinoline hydrazide as a novel model in fungicide innovation.

Chromatography-Free Synthesis of ß-Carboline 1-Hydrazides and an Investigation of the Mechanism of Their Bioactivity: The Discovery of ß-Carbolines as Promising Antifungal and Antibacterial Candidates.

Agrochemical science prioritizes the discovery and effective synthesis of innovative and promising lead compounds. Herein, we developed an efficient column chromatography-free synthesis for ß-carboline 1-hydrazides via a mild CuBr2-catalyzed oxidation and investigated the antifungal and antibacterial activities and mechanisms for these compounds. In our study, compounds 4de (EC50 = 0.23 µg·mL-1) and 4dq (EC50 = 0.11 µg·mL-1) displayed the best efficacy, demonstrating enhancements in inhibitory activity of more than 20-fold against Ggt compared to silthiopham (EC50 = 2.39 µg·mL-1). Additionally, compound 4de (EC50 = 0.21 µg·mL-1) demonstrated outstanding in vitro antifungal activities as well as in vivo curative activities against Fg. According to preliminary mechanistic studies, ß-carboline 1-hydrazides led to the accumulation of reactive oxygen species, destruction of cell membranes, and dysregulation of histone acetylation. Furthermore, several substances exhibited antibacterial activity against Psg and Cms by preventing the development of bacterial biofilms.

Practical Synthesis and Antifungal Investigation of Drimane Meroterpenoids Enabled by Nickel-Catalyzed Decarboxylative Coupling.

Drimane meroterpenoids have drawn increasing attention in the discovery of novel pharmaceutical leads owing to their structural diversity and bioactivity variation, but further development is significantly impeded by the lack of an efficient modular route of preparation. A nickel-catalyzed decarboxylative cross-coupling paradigm has been established to expeditiously access a constellation of drimane meroterpenoids. The redox-active drimane precursor is a bench-stable coupling partner and is easily available from the inexpensive feedstock sclareol. This transformation features the tolerance of challenging functional groups (phenol, aldehyde, ester, etc.) and mild conditions with a low-cost nickel catalytic system. The synthetic utility is further highlighted by the direct scalable synthesis of challenging drimane meroterpenoids as diversifiable advanced intermediates for late-stage functionalizations. This method facilitated antifungal investigations and culminated in the discovery of compounds C8 and C3 as new antifungal leads against Rhizoctonia solani, with EC50 values of 4.9 and 7.2 µM, respectively.

The application of a novel hydrodynamic cavitation device to debride intra-articular monosodium urate crystals.

INTRODUCTION: Efficient and complete debridement of intra-articular deposits of monosodium urate crystals is rarely achieved by existing arthroscopic tools such as shavers or radiofrequency ablation, while cavitation technology represents a prospective solution for the non-invasive clearance of adhesions at intra-articular interfaces. METHODS: Simulation modeling was conducted to identify the optimal parameters for the device, including nozzle diameters and jet pressures. Gouty arthritis model was established in twelve rats that were equally and randomly allocated into a cavitation debridement group or a curette debridement group. A direct injection nozzle was designed and then applied on animal model to verify the effect of the cavitation jet device on the removal of crystal deposits. Image analysis was performed to evaluate the clearance efficiency of the cavitation device and the pathological features of surrounding tissue were collected in all groups. RESULTS: To maximize cavitation with the practical requirements of the operation, an experimental rig was applied, including a 1 mm direct injection nozzle with a jet pressure of 2.0 MPa at a distance of 20 mm and a nitrogen bottle as high-pressure gas source. With regards to feasibility of the device, the clearance rates in the cavitation group were over 97% and were significantly different from the control group. Pathological examination showed that the deposition of monosodium urate crystals was removed completely while preserving the normal structure of the collagen fibers. CONCLUSIONS: We developed a promising surgical device to efficiently remove intra-articular deposits of monosodium urate crystals. The feasibility and safety profile of the device were also verified in a rat model. Our findings provide a non-invasive method for the intraoperative treatment of refractory gouty arthritis.

Asymmetric Synthesis of Sakuranetin-Relevant Flavanones for the Identification of New Chiral Antifungal Leads.

Discovery and efficient synthesis of new promising leads have a central role in agrochemical science. Reported herein is the sakuranetin-directed synergistic exploration of an asymmetric synthesis and an antifungal evaluation of chiral flavanones. A new palladium catalytic system with CarOx-type ligands was successfully identified for the highly enantioselective addition of arylboronic acids to chromones. This enabled the facile and programmable construction of a constellation of chiral flavanones (up to 98% yield and 97% ee), in which (R)-pinostrobin was efficiently constructed without laborious protecting/deprotecting operations. Its good performance in asymmetric induction and functional tolerance expanded the chemical space of pharmaceutically important flavanones. The chiral differentiation of flavanones based on antifungal activity and a concise structure-activity relationship model was disclosed and summarized. This synergistic project culminated with acquisition of the naturally unprecedented flavanones with better antifungal potentials than sakuranetin, in which the R-enantiomer of flavanone 54 (EC50 = 0.8 µM) demonstrated better performance than boscalid against Rhizoctonia solani. The novel scaffold and predicted new target compared with the commercial fungicides in the FRAC reinforce the value of further exploration.

Palladium Catalyzed Enantioselective Hayashi-Miyaura Reaction for Pharmaceutically Important 4-Aryl-3,4-dihydrocoumarins.

The first palladium-catalyzed asymmetric addition of arylboronic acids to coumarins was successfully established, providing a straightforward asymmetric approach to achieving pharmaceutically important 4-aryl-3,4-dihydrocoumarins. This methodology features easily accessible and bench-stable ligands, a wide substrate scope, mild conditions, and accommodation of electron-withdrawing arylboronic acids.

Facile and divergent optimization of chromazonarol enabled the identification of simplified drimane meroterpenoids as novel pharmaceutical leads.

The diversity of drimane hydroquinones was significantly expanded by the facile construction of (+)-chromazonarol relevant natural products, isomers, and analogues for the discovery of new pharmaceutical leads. The structure-activity relationship of (+)-chromazonarol relevant (non)-natural products was delineated via the synergistic interaction of the programmable synthesis and bioactivity-guided screening. The first divergent derivatization of (+)-chromazonarol demonstrated that the phenolic hydroxyl group is one inviolable requirement for antifungal effect. Pinpoint modification of (+)-yahazunol manifested the position of hydroxyl group was crucial for both antifungal and antitumor activities. (+)-Albaconol, (+)-neoalbaconol, and two (+)-yahazunol isomers (24 and 25) proved to be the novel pharmaceutical leads. The probable macromolecular targets were estimated to deliver new information about the biological potentials resident in (+)-yahazunol relevant products. This work also featured the first synthesis of (+)-albaconol and (+)-neoalbaconol, the first biological exploration of (+)-dictyvaric acid and improved preparation of (+)-8-epi-puupehedione and a promising pelorol analogue.

Radial Extracorporeal Shock Wave Therapy Enhances Graft Maturation at 2-Year Follow-up After ACL Reconstruction: A Randomized Controlled Trial.

Background: Graft maturation is an important prognostic factor for hamstring autograft anterior cruciate ligament reconstruction (ACLR). It remains unclear whether extracorporeal shock wave therapy (ESWT) can promote graft healing after ACLR. Purpose: To evaluate the therapeutic and graft maturation effects of ESWT in hamstring autograft ACLR. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Between May 18, 2019, and September 20, 2019, we randomly assigned 30 patients who met study inclusion criteria to 2 groups. Patients in the control group followed a 5-week advanced rehabilitation training program (30 minutes/session, 5 times/week) starting at 3 months postoperatively. In the ESWT group, together with the 5-week advanced rehabilitation training, radial ESWT was applied once a week for 5 weeks. Functional scores (Lysholm, International Knee Documentation Committee, and Tegner scores), KT-1000 arthrometer knee laxity measurement, and magnetic resonance imaging scans were assessed at 3 months (baseline), 6 months, and 24 months postoperatively. To evaluate graft maturation, we assessed the graft signal-to-noise quotients (SNQs) of the tibial, intra-articular, and femoral sides on magnetic resonance imaging scans. Data were compared between the ESWT and control groups. Results: In total, 26 patients (13 with ESWT, 13 controls) were assessed. There were no significant between-group differences on any assessment at baseline, and no significant within-group or between-group differences were found in knee laxity at any point. At 24-month follow-up, the ESWT group had significantly higher Lysholm and Tegner scores compared with the controls (P = .012 and .017, respectively). Regarding graft maturation, at 6-month follow-up, the SNQ of the tibial intraosseous graft was significantly lower in the ESWT group versus controls (P = .006), but no differences were detected at the femoral intraosseous graft (P = .321) or the intra-articular graft (P = .314). At 24-month follow-up, the SNQs of the femoral intraosseous graft and intra-articular graft were significantly lower in the ESWT group versus controls (P = .020 and .044, respectively) but no difference was found at the tibial intraosseous graft (P = .579). Conclusion: Both enhanced graft maturation and improved functional scores at 24-month follow-up were seen in patients who received radial ESWT during rehabilitation after hamstring autograft ACLR. Registration: ChiCTR1900022853 (Chinese Clinical Trial Registry).

Deactivation of the dorsal anterior cingulate cortex indicated low postoperative sports levels in presurgical patients with chronic ankle instability.

BACKGROUND: Injury-related fear contributed to disability in chronic ankle instability (CAI), while there still lacked exploration on the appraisal processes of the injury-related stimuli. This study aimed to compare the neural activities of the appraisal processes of sprain-related stimuli between presurgical chronic ankle instability patients and healthy controls through functional magnetic resonance imaging (fMRI) and evaluate its relationships with the clinical outcomes of orthopedic surgeries. METHODS: Eighteen presurgical CAI patients and fourteen healthy controls were recruited and underwent an fMRI session with visual stimulation of movies that showing typical ankle sprains accidents or control videos and the corresponding fear ratings. The clinical outcomes were collected at baseline and a minimum of 2 years after surgery; these included the American Orthopaedic Foot and Ankle Society (AOFAS) scores, the Numeric Rating Scale (NRS) scores, and the Tegner Activity Rating Scale scores. The two-sample t-test would be applied to identify which brain regions were influenced by CAI, and the correlation analysis would be applied to measure the relationship between the activation and clinical outcomes. RESULTS: Dorsal anterior cingulate cortex (dACC) was deactivated in CAI patients when compared with healthy controls, and the dACC deactivation strength revealed a moderate correlation with the values of fear ratings for all participants. The deactivation strength was negatively correlated with AOFAS at baseline, with Tegner at follow-up and its improvement. CONCLUSIONS: Presurgical CAI patients presented deactivated dACC as a different neural activity of appraisal processes of sprain-related stimuli when compared with healthy controls, which was associated with lower postoperative sports levels. More comprehensive patients care including psychological interventions were needed in the clinical management of chronic ankle instability.

Minimally Invasive Embedding of Saturated MSU Induces Persistent Gouty Arthritis in Modified Rat Model.

INTRODUCTION: Animal models are valid for in vivo research on the pathophysiological process and drug screening of gout arthritis. Intra-articular injection of monosodium urate (MSU) is the most common method, while stable MSU deposition enveloped by inflammatory cells was rarely reported. OBJECTIVE: To develop a modified gouty arthritis rat model characterized by intra-articular MSU deposition and continuous joint pain with a minimally invasive method. METHOD: A total of twenty-four rats were randomly allocated into six groups. Three intervention groups of rats received intra-articular MSU embedment. Sham groups received pseudosurgeries with equal normal saline (NS). Gross parameters and pathological features of synovium harvested from anterior capsule were estimated. Mechanical pain threshold tests were conducted over a 96-hour period postoperatively. Moreover, quantitative immunofluorescence was conducted to assess tissue inflammation. RESULT: After MSU embedding, rats got more persistent arthritic symptoms as well as tissue MSU deposition. More significant synovial swelling was detected in the MSU group compared to sham groups (P < 0.025). Behavioral tests showed that the embedding of MSU resulted in prolonged mechanical hyperalgesia during 2 hours to 96 hours postoperatively (P < 0.05). MSU depositions enveloped by inflammatory cells that express IL-1ß and TNF-α were detected in embedding groups. Quantitative immunofluorescence suggested that the frequencies of MSU interventions upregulated expression of proinflammatory factors including IL-1ß and TNF-α (P < 0.05). CONCLUSION: A minimally invasive method was developed to establish modified rat model of intra-articular MSU deposition. This model was proved to be a simple reproducible method to mimic the pathological characteristics of persistent gouty arthritis.

Lateral ankle instability-induced neuroplasticity in brain grey matter: A voxel-based morphometry MRI study.

OBJECTIVES: The deficits in sensory pathways caused by peripheral edema, pain, and inflammation of the damaged ligaments may induce maladaptive changes within the central nervous system. The purpose of this study was to determine whether patients with lateral ankle instability (LAI) exhibit morphological differences of brain grey matter when compared with healthy controls, and then assess the relationships between the observed differences and the characteristics of patients. DESIGN: Cross-sectional. METHODS: Thirty patients with LAI and 32 healthy controls without LAI underwent MRI scans using anatomical T1 sequences. A voxel-wise general linear model was used to compare the grey matter volume throughout the whole brain between patients and controls. Linear regression analyses were performed for the grey matter volume within the significant clusters to assess their relationship with age, sex, the existence of acute injury, pain level, sports activity level, and the duration of LAI within the patient group. RESULTS: The grey matter volume of a cluster within the cerebellar vermis (Vermis_4_5 in automated anatomical labeling template) was significantly reduced in patients with LAI (Gaussian Random Field corrections with two-tailed p-cluster < 0.05 and p-voxel < 0.001). Multivariate linear regression analysis revealed that the duration of LAI tended to be passively associated with the grey matter volume of this LAI-related vermal cluster (p = 0.092). CONCLUSIONS: Participants with LAI exhibited a reduced grey matter volume of a cluster within the cerebellar vermis compared with participants without LAI, and the degree of volume reduction tended to be positively associated with the duration of LAI.

Outcomes of arthroscopic bone graft transplantation for Hepple stage V osteochondral lesions of the talus.

BACKGROUND: Based on MRI imaging findings, osteochondral lesions of the talus (OLT) can be classified into five stages, in which stage V represents OLT with subchondral cyst formation. The aim of this study was to evaluate the outcomes of patients undergoing arthroscopic transplantation of calcaneus bone graft for Hepple stage V OLT. METHODS: This retrospective study included 24 patients with Hepple stage V OLT (15 men and 9 women), with an average age of 39.8±12.9 years old. The mean follow-up period was 18.9±11.8 months. At this follow-up, all patients were clinically evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) score, the Karlsson Ankle Function Score (KAFS), the Tegner score, and the visual analogue scale (VAS). Furthermore, 14 patients underwent MRI imaging examinations, and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score was assessed. RESULTS: The AOFAS score, KAFS, Tegner activity score, and VAS pain score (preoperative: 62.2, 60.4, 2.1, and 6.2, respectively; postoperative: 92.8, 88.5, 4.2, and 1.6, respectively) improved significantly (P=0.0001). The MRI-based MOCART score of the articular cartilage repair tissue after surgery was 68±14.8. CONCLUSIONS: Arthroscopic transplantation of calcaneus bone graft for Hepple stage V OLT could obtain satisfying clinical and radiological outcomes in the short-term.

Discovery and preliminary mechanism of 1-carbamoyl ß-carbolines as new antifungal candidates.

Natural ß-carboline alkaloids are ideal models for the discovery of pharmaceutically important entities. Various 1-substituted ß-carbolines were synthesized from commercially inexpensive tryptophan and demonstrated significant in vitro antifungal activity against G. graminis. Significantly, compound 4m (EC50 = 0.45 µM) with carboxamide at 1-position displayed the best efficacy and nearly 20 folds enhancement in antifungal potential compared to Silthiopham (EC50 = 8.95 µM). Moreover, compounds 6, 7, and 4i exhibited excellent in vitro antifungal activities and in vivo protective and curative activities against B. cinerea and F. graminearum. Preliminary mechanism studies revealed that compound 4m caused reactive oxygen species accumulation, cell membrane destruction, and deregulation of histone acetylation. These findings indicated that 1-carbamoyl ß-carboline can be selected as a promising model for the discovery of novel and broad-spectrum fungicide candidates.

Soil wind erosion evaluation and sustainable management of typical steppe in Inner Mongolia, China.

Soil wind erosion is an important ecological environmental problem that is widespread in arid and semi-arid regions. Currently, related studies are mainly focused on spatiotemporal characteristics or analysis of effector mechanisms, and they do not facilitate direct servicing of management decisions. In this paper, we used the Xilingol typical steppe in Inner Mongolia, China, as a study site to develop a decision framework for a comprehensive understanding of soil wind erosion and to promote sustainable management of steppes. In this study, we used the Revised Wind Erosion Equation model to simulate soil wind erosion. We combined this model with linear trend analysis to evaluate the ecological effects of soil wind erosion and wind erosion intensity, and delineated the gravity center migration path. We used the constraint line method to reveal the mechanisms by which climatic factors affected soil wind erosion, achieved the spatial visualization of wind-breaking and sand-fixing service flow, and proposed decision-based regional sustainable development suggestions. The results showed that long-term soil wind erosion will lead to soil coarsening and loss of soil nutrients. Soil wind erosion in the study site showed worsening trends and risks, and as such, ecological environment conservation and management are urgently required. The study framework promotes a clear understanding of the complex relationship of human-earth systems. The study results will aid in the ecological remediation of steppe landscapes and the prevention of desertification and will provide a foundation for win-win management of ecological conservation and economic development in arid and semi-arid regions.

Modular Synthesis of Drimane Meroterpenoids Leveraging Decarboxylative Borylation and Suzuki Coupling.

Drimane meroterpenoids have attracted an increasing amount of attention in the discovery of therapeutically important probes, while the laggard synthetic accessibility is a conspicuous challenge. A new paradigm merging decarboxylative borylation and Suzuki coupling was developed as a powerful platform. Key features include the mild conditions, good chemoselectivity, operational facility, scalability, and easy availability of the coupling partners. This practical strategy enables the expedient formal synthesis of a large number of natural products and rapid generation of analogues.

Nanowire Ring Embedded in a Flexible Substrate for Local Strain Detection.

Optical sensing has attracted more and more attention in recent years with the advance in planar waveguide fabrication processes. The photon, as a carrier of information in sensing areas, could have a better performance than electrons. We propose a novel end-to-end ring cavity to fabricate sensitive units of a strain sensor. We then propose a method of combining a flexible substrate with an end-to-end semiconductor nanowire ring cavity to fabricate novel strain sensors. We used a tuning resonant wavelength detected by a homebuilt excitation and detection system to measure applied strain. The resonant wavelength of the strain gauge was red-shift and linear tuned with increasing strain. The gauge factor was about 50, calculated through experiments and theory, and Q was 1938, with structural parameters L = 70 µm and d = 1 µm. The high sensitivity makes it possible to measure micro deformation more accurately. End-to-end coupling active nanowire waveguides eliminate the shortcomings of side by side coupling structures, which have the phasing shift with no minor optical density loss. This resonator in flexible substrates could be used not only as on-chip strain sensors for micro or nano deformation detecting but also as tunable light sources for photonic integrated circuits.