The key mediator of diabetic kidney disease: Potassium channel dysfunction.

Diabetic kidney disease is a leading cause of end-stage renal disease, making it a global public health concern. The molecular mechanisms underlying diabetic kidney disease have not been elucidated due to its complex pathogenesis. Thus, exploring these mechanisms from new perspectives is the current focus of research concerning diabetic kidney disease. Ion channels are important proteins that maintain the physiological functions of cells and organs. Among ion channels, potassium channels stand out, because they are the most common and important channels on eukaryotic cell surfaces and function as the basis for cell excitability. Certain potassium channel abnormalities have been found to be closely related to diabetic kidney disease progression and genetic susceptibility, such as KATP, KCa, Kir, and KV. In this review, we summarized the roles of different types of potassium channels in the occurrence and development of diabetic kidney disease to discuss whether the development of DKD is due to potassium channel dysfunction and present new ideas for the treatment of DKD.

The Impact of Marijuana Use on Postoperative Outcomes in Abdominal-based Free Flap Breast Reconstruction.

BACKGROUND: There is an increasing prevalence of marijuana use in the general population yet clinical studies on marijuana's effect on surgical outcomes remain limited. Marijuana's effect on wound healing, venous thromboembolism (VTE) due to endothelial inflammation, and bleeding due to inhibited platelet function have been cited based on animal models but have not been evaluated clinically in patients undergoing microsurgical reconstruction. METHODS: Retrospective chart review was performed on all patients who underwent abdominal-based free flap breast reconstruction in a single institute from August 2018 to December 2022. Patient self-reported marijuana use, demographics, total narcotic use during hospitalization converted to oral morphine milligram equivalent (MME), and 90-day complications were collected and compared. RESULTS: A total of 162 patients were included and 13 patients (8.5%) had reported marijuana use on presurgical history. Marijuana users are more likely to be younger and report concurrent nicotine smoking. Marijuana users were also at a significantly elevated risk of developing symptomatic VTE (15 vs. 1%; odds ratio (OR) 13.4 [95% confidence interval (CI) 1.71-104.2]; p = 0.01) and marijuana use remained a significant risk factor with multivariate analysis. On postoperative 90-day complications, there was no increased risk of flap loss, reoperation, postoperative transfusion, or hematoma associated with marijuana use, and no significantly increased risk for overall donor or recipient site complications. Marijuana users required significantly more narcotics for pain control during hospitalization (100 ± 77 vs. 49 ± 45 MME; p = 0.0003), although they had similar lengths of stay, achievement of mobilization on post operative day (POD)1, and maximal pain scores. CONCLUSION: Marijuana use increases the risks of postoperative VTE and increased postoperative narcotic requirements in patients who underwent abdominal-based free flap breast reconstruction. Future prospective cohort study is required to further understand marijuana-associated risks in microsurgical procedures.

Postoperative Magnesium Sulfate Repletion Decreases Narcotic Use in Abdominal-Based Free Flap Breast Reconstruction.

BACKGROUND: Microsurgical breast reconstruction after mastectomy is now the standard of care for breast cancer patients. However, the costs and resources involved in free flap reconstruction can vary across different medical settings. To enhance patient outcomes in a cost-effective manner, we investigated the effect of intravenous magnesium sulfate (IV Mg) on postoperative opioid usage in this context. METHODS: A retrospective chart review was performed on all consecutive patients who underwent abdominal-based free flap breast reconstruction in a single institute following an enhanced recovery after surgery (ERAS) protocol. Patients who received IV Mg were compared with those who did not receive supplementation. Serum magnesium levels at different time points, narcotic consumption in units of oral morphine milligram equivalents (MMEs), and other postoperative recovery parameters were compared. RESULTS: Eighty-two patients were included. Those who received IV Mg on postoperative day 0 (n = 67) showed significantly lower serum magnesium levels before repletion (1.5 vs. 1.7 mg/dL, p = 0.004) and significantly higher levels on postoperative day 1 after repletion (2.2 vs. 1.7 mg/dL, p = 0.0002) compared to patients who received no magnesium repletion (n = 13). While both groups required a similar amount of narcotics on postoperative day 0 (20.2 vs. 13.2 MMEs, p = 0.2), those who received IV Mg needed significantly fewer narcotics for pain control on postoperative day 1 (12.2 MMEs for IV Mg vs. 19.8 MMEs for No Mg, p = 0.03). Recovery parameters, including maximal pain scores, postoperative mobilization, and length of hospital stay, did not significantly differ between the two groups. CONCLUSION: This is the first study to describe the potential analgesic benefits of routine postoperative magnesium repletion in abdominal-based free flap reconstruction. Further research is necessary to fully understand the role of perioperative magnesium supplementation as part of an ERAS protocol.

Women in Microsurgery Fellowships: Trends and Impact on Future Practice Patterns.

BACKGROUND: While the number of female plastic surgeons has continued to increase over time, plastic surgery has historically been a male-dominated profession with only 15% of practicing plastic surgeons being female. Microsurgery, as a subspecialty, has been long perceived as an even more male-centric career path. The objective of this study was to determine the representation of females in the subspecialty field of microsurgery and the impact of microsurgical fellowship training. METHODS: A review of all microsurgery fellowship programs participating in the microsurgery fellowship match from 2010 to 2019 were analyzed. Fellows were identified through fellowship Web site pages or direct contact with fellowship program coordinators and directors. The current type of practice and performance of microsurgery were also identified through a Web search and direct contact with fellowship program coordinators and directors. RESULTS: A total of 21 programs and 317 fellows over a 10-year period were analyzed. Over this 10-year period, there was a total of 100 (31.5%) female microsurgery fellows and 217 (68.5%) male microsurgery fellows. There was a small, statistically insignificant increase in the yearly percentage of female microsurgery fellows over this 10-year period with an average yearly increase of 2.7% (p = 0.60; 95% confidence interval: -6.9 to 13.2%). There were significantly fewer females who continued to practice microsurgery compared to males (75 [75.0%] vs. 186 [85.7%], p = 0.02). There was no significant difference in the current practice types (academic, private, and nonacademic hospital) between females and males (p = 0.29). CONCLUSION: Women are underrepresented in the field of microsurgery to a similar extent as they are underrepresented in overall plastic surgery. While there is a small insignificant increase in the number of female microsurgery fellows every year, a significantly smaller proportion of females continue to practice microsurgery compared to males.

Oncologic Safety in Autologous Fat Grafting After Breast Conservation Therapy: A Systematic Review and Meta-analysis of the Literature.

BACKGROUND: Autologous fat grafting (AFG) is often used to reconstruct defects after breast conservation therapy (BCT). However, concerns exist about the possibility of AFG-related recurrence or metastasis. This study aims to evaluate the literature to evaluate oncologic outcomes in patients undergoing AFG at the time of BCT. METHODS: A systematic review of articles related to AFG based reconstruction at the time of BCT from 1970 to 2021 was performed via PubMed. Patients were grouped based on the presence or lack of AFG usage at the time of BCT, and oncologic outcomes and complications were compared. RESULTS: Of the 146 articles identified, 15 were included. Nine hundred patients underwent BCT alone and 1063 patients underwent BCT with AFG patients. Similar average follow-up time was observed between the groups, 58.7 months (BCT only) and 55.2 months (BCT with AFG). On pooled analysis, no difference was identified in local recurrence 4.8% (43 patients) of the BCT group and 3% (32 patients) in the AFG group (P = 0.8), metastasis 4.8% (43 patients) of the BCT group and 6.9% (73 patients) in the AFG group (P = 0.3), or fat necrosis (P = 0.44). Meta-analysis additionally did not identify any statistically significant odds ratios between the BCT only group and BCT with AFG group when evaluated for total recurrence, local recurrence, metastasis or fat necrosis. CONCLUSIONS: The results show no significant difference in cancer recurrence or metastasis in the BCT only group versus BCT and AFG, showing that fat grafting has safe outcomes.

The Palpable Nodule after Autologous Fat Grafting: Distinguishing Benign versus Malignant Lesions in Breast Reconstruction.

BACKGROUND: Nodule formation after autologous fat grafting to the breast is the most common complication. In the reconstructive population, this generates significant patient anxiety and presents a diagnostic challenge. The authors characterized palpable nodule occurrence after autologous fat grafting in breast reconstruction and compared benign versus malignant nodule characteristics. METHODS: Chart review of the senior author's experience with breast fat grafting was performed. Data extracted included demographics, intraoperative details, nodule data, radiographic characteristics, and biopsy results. Logistic regression identified risk factors for nodule formation. Unpaired t tests and Fisher exact tests compared characteristics of benign versus malignant nodules. RESULTS: In total, 775 breasts were identified that underwent 1158 fat grafting procedures, of which 67 (8.6 percent) developed palpable nodules. Sonographic characterization of nodules included presumed fat necrosis (38.2 percent), benign lesions (27.6 percent), presumed oil cysts (17.1 percent), indeterminate (8.9 percent), and concerning for malignancy (8.1 percent). Lesions concerning for malignancy were more often irregular (10.0 percent versus 0 to 2.9 percent of benign nodules) and more often larger than 0.8 cm in greatest dimension (80 percent versus 42.9 to 61.8 percent of benign nodules). Six patients developed a palpable local recurrence. Malignant nodules tended to be larger (1.45 cm versus 0.70 cm; p = 0.03), were more often vascular (50 percent versus 3.8 percent; p = 0.03), and tended to occur later (17.5 months versus 10.0 months; p = 0.60). Benign nodules occurred in the setting of larger fat graft volumes (64.2 cc versus 40.0 cc; p = 0.008). CONCLUSION: This study provides the first comparison of radiographic and clinical characteristics between benign and malignant palpable nodules after autologous fat grafting in breast reconstruction. CLINICAL QUESTION/LEVEL OE EVIDENCE: Risk, III.

Modeling of Bimodular Bone Specimen under Four-Point Bending Fatigue Loading.

The fatigue damage behavior of bone has attracted significant attention in both the mechanical and orthopedic fields. However, due to the complex and hierarchical structure of bone, describing the damage process quantitively or qualitatively is still a significant challenge for researchers in this area. In this study, a nonlinear bi-modulus gradient model was proposed to quantify the neutral axis skewing under fatigue load in a four-point bending test. The digital image correlation technique was used to analyze the tensile and compressive strains during the fatigue process. The results showed that the compressive strain demonstrated an obvious two-stage ascending behavior, whereas the tensile strain revealed a slow upward progression during the fatigue process. Subsequently, a theoretical model was proposed to describe the degradation process of the elastic modulus and the movement of the neutral axis. The changes in the bone properties were determined using the FEM method based on the newly developed model. The results obtained from two different methods exhibited a good degree of consistency. The results obtained in this study are of help in terms of effectively exploring the damage evolution of the bone materials.

Establishment of Objective Clinical Parameters for Assessment of Trigonocephaly: Are Caliper-Derived Clinical Measures Adequate?

OBJECTIVE: Objective clinical parameters characterizing the severity of trigonocephaly are essential given the concern for computerized tomography (CT) scans and radiation in infants. The present study seeks to develop a clinical tool by which to characterize trigonocephaly. DESIGN: Retrospective cohort study. SETTING: Tertiary academically affiliated children's medical center. PARTICIPANTS: A retrospective review identified patients with trigonocephaly for whom surgery was recommended (group 1) and those with metopic ridging without significant trigonocephaly (group 2). Normal age-matched controls were also evaluated (group 3). INTERVENTIONS: Cranial vault caliper measurements were compared across groups. Two ratios measuring anterior vault constriction were developed: (1) bitemporal width at the mid-forehead to the biparietal width, and (2) bitemporal width at the lateral brow to the biparietal width. MAIN OUTCOME MEASURES: Bitemporal width to biparietal width (ratio). RESULTS: Caliper measures were obtained from 19 patients in group 1, 8 patients in group 2, and 19 patients in group 3 (controls). Cranial indices were not significantly different across groups. The bitemporal width at the mid-forehead to the biparietal width ratio was significantly lower in group 1, with no difference between groups 2 and 3. The bitemporal width at the lateral brow to the biparietal width ratio was significantly different between all 3 groups, with group 1 < group 2 < group 3, respectively. CONCLUSIONS: Bitemporal to biparietal ratios are a quantitative, objective clinical measure that can be used to differentiate patients with significant trigonocephaly from those with metopic ridging but no significant cranial deformity. These findings suggest that caliper-derived indices can assist in characterizing surgically relevant cranial vault deformities secondary to metopic synostosis and may circumvent CT-based analysis.

Acellular Dermal Matrix-Associated Contracture: A Clinical and Histologic Analysis of Patients Undergoing Prosthetic Breast Reconstruction.

BACKGROUND: Capsular contracture is a well-recognized complication following prosthetic breast reconstruction. It has been the authors' observation that some patients undergoing breast reconstruction experience contracture specifically of the acellular dermal matrix placed at the time of their tissue expander insertion. The goal of the authors' study was to identify clinical and histologic findings associated with the development of acellular dermal matrix-associated contracture. METHODS: The authors performed a retrospective cohort study of all patients undergoing bilateral implant-based breast reconstruction performed by the senior author (M.S.A.). Patients were excluded if they had radiation therapy to the breast. Patients with suspected acellular dermal matrix-associated contracture were identified by clinical photographs and review of operative notes. Histologic analysis was performed on specimens taken from two patients with acellular dermal matrix contracture. RESULTS: The authors included a total of 46 patients (92 breasts), of which 19 breasts had suspected acellular dermal matrix-associated contracture. Acellular dermal matrix contracture was less common in direct-to-implant reconstruction (4.2 percent versus 26.5 percent; p = 0.020) and more common in breasts that had seromas (0 percent versus 15.8 percent; p = 0.001) or complications requiring early expander replacement. Contracted acellular dermal matrix had less vascularity and a lower collagen I-to-collagen III ratio, and was twice as thick as noncontracted acellular dermal matrix. CONCLUSIONS: The authors have described a distinct phenomenon of acellular dermal matrix-associated contracture that occurs in a small subset of breasts where acellular dermal matrix is used. This merits further investigation. Future work will be required to better characterize the clinical factors that make acellular dermal matrix-associated contracture more likely to occur. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Use of PROMIS® to screen for depression in children with arthritis.

BACKGROUND: Children with JIA may experience difficulty with health related quality of life (HRQOL). The Patient Reported Outcomes Measurement Information System (PROMIS) a patient related outcome (PRO) measure, covers HRQOL domains that include physical function, mental health, and social interactions. During initial use, we found PROMIS identified children with symptoms of depression, sometimes before they shared those feelings with parents or members of the clinic team. We studied the use of PROMIS for this purpose, and to determine what demographic, clinical, and other characteristics might be related to higher depressive symptom scores. METHODS: From March 2014 - February 2017, at each visit, all JIA patients having met ILAR classification criteria seen by M.L.M. received the PROMIS Short Form 35 v.1.0, as part of routine care. T scores were calculated from raw scores for mobility, anxiety, depressive symptoms, fatigue, peer relationships, and pain interference domains. Data extracted by optical mark recognition software were merged with electronic medical record (EMR data), extracted by Extract/Transform/Load software, including joint counts, visit age, ANA, RF, and HLA-B27 status. Mixed effects models were used to identify significant associations of independent variables with depression T scores. RESULTS: Data from 148 patients were analyzed (114 females for 435 visits, 34 males for 118 visits; 13.8 ± 2.8 years): 70 persistent oligoarthritis, 9 extended oligoarthritis, 19 ERA, 21 polyarthritis (RF-), 5 polyarthritis (RF+), 11 undifferentiated arthritis, 3 psoriatic arthritis, 10 systemic arthritis). T scores showed wide ranges within individual JIA categories, with similar mean scores for all groups. Univariate linear mixed effects models showed significant relationships to depression T scores of gender and race (males and Asian patients with lower T scores, p < .0001, p = 0.091, respectively), joint count (p = 0.002), pain interference score (p = 0.0004), and Patient and Physician Global Assessment (p = 0.004, p < .0001, respectively). No particular JIA category was associated with Depression T scores. HRQOL domains were interrelated (p < .0001), including patients reporting symptoms of depression tending also to report symptoms of anxiety. PROMIS identified 15 patients who did not otherwise report depressive symptoms, but needed referral for counseling; eight did not endorse depressive symptoms until the 2nd or 3rd visit. Only 3 patients had disease flare. Concerns besides arthritis such as parental conflict or school bullying were elicited in 7 patients during interviews with the social worker. All patients expressed being worried about their arthritis. CONCLUSION: PROMIS is useful in screening JIA patients for symptoms of depression, particularly to identify patients who might not otherwise report these symptoms. The other PROMIS domain scores are related to reporting of symptoms of depression, as is Patient and Physician Global Assessment. Future studies will use PROMIS questionnaires incorporated into the EMR, permitting data entry by tablets and an online patient portal. This will make possible comparisons of HRQOL in children with JIA to those with other chronic rheumatic and non-rheumatic diseases.

Spring-Assisted Distraction Osteogenesis for the Treatment of Shunt-Induced Craniosynostosis.

Shunt-induced craniosynostosis is a rare complication of ventricular shunting for hydrocephalus in pediatric patients. Although the exact pathophysiology of this form of secondary craniosynostosis is not well understood, the current understanding is that persistent drainage of the ventricular shunt causes decreased dural tension, resulting in decreased expansile force on the cranium and premature sutural fusion. Due to the low incidence of this complication, there is no consensus on the ideal treatment for shunt-induced craniosynostosis. In recent years, distraction osteogenesis has been employed with greater frequency, as it is felt to counter the fundamental problem of decreased expansile force on the cranium. However, in a patient with a ventricular shunt, placement of external hardware in close proximity to the shunt could cause significant morbidity due to the increased risk of shunt infection. We present the management of a patient with shunt-induced craniosynostosis who continued to be shunt-dependent. We chose to use fully buried springs to create an expansile force on the cranium as an alternative to external distractors so as to mitigate the risk of infection. We demonstrate that spring-assisted distraction osteogenesis can be an effective treatment modality for patients with shunt-induced craniosynostosis. This method should be considered in patients with contraindications to external distraction devices, such as ongoing shunt dependency.

SIRT2 deletion enhances KRAS-induced tumorigenesis in vivo by regulating K147 acetylation status.

The observation that cellular transformation depends on breaching a crucial KRAS activity threshold, along with the finding that only a small percentage of cellsharboring KRAS mutations are transformed, support the idea that additional, not fully uncovered, regulatory mechanisms may contribute to KRAS activation. Here we report that KrasG12D mice lacking Sirt2 show an aggressive tumorigenic phenotype as compared to KrasG12D mice. This phenotype includes increased proliferation, KRAS acetylation, and activation of RAS downstream signaling markers. Mechanistically, KRAS K147 is identified as a novel SIRT2-specific deacetylation target by mass spectrometry, whereas its acetylation status directly regulates KRAS activity, ultimately exerting an impact on cellular behavior as revealed by cell proliferation, colony formation, and tumor growth. Given the significance of KRAS activity as a driver in tumorigenesis, identification of K147 acetylation as a novel post-translational modification directed by SIRT2 in vivo may provide a better understanding of the mechanistic link regarding the crosstalk between non-genetic and genetic factors in KRAS driven tumors.

SIRT2-Mediated Deacetylation and Tetramerization of Pyruvate Kinase Directs Glycolysis and Tumor Growth.

Sirtuins participate in sensing nutrient availability and directing metabolic activity to match energy needs with energy production and consumption. However, the pivotal targets for sirtuins in cancer are mainly unknown. In this study, we identify the M2 isoform of pyruvate kinase (PKM2) as a critical target of the sirtuin SIRT2 implicated in cancer. PKM2 directs the synthesis of pyruvate and acetyl-CoA, the latter of which is transported to mitochondria for use in the Krebs cycle to generate ATP. Enabled by a shotgun mass spectrometry analysis founded on tissue culture models, we identified a candidate SIRT2 deacetylation target at PKM2 lysine 305 (K305). Biochemical experiments including site-directed mutants that mimicked constitutive acetylation suggested that acetylation reduced PKM2 activity by preventing tetramerization to the active enzymatic form. Notably, ectopic overexpression of a deacetylated PKM2 mutant in Sirt2-deficient mammary tumor cells altered glucose metabolism and inhibited malignant growth. Taken together, our results argued that loss of SIRT2 function in cancer cells reprograms their glycolytic metabolism via PKM2 regulation, partially explaining the tumor-permissive phenotype of mice lacking Sirt2 Cancer Res; 76(13); 3802-12. ©2016 AACR.

SIRT3 and SIRT4 are mitochondrial tumor suppressor proteins that connect mitochondrial metabolism and carcinogenesis.

It is a well-established scientific observation that mammalian cells contain fidelity proteins that appear to protect against and adapt to various forms of endogenous and exogenous cellular conditions. Loss of function or genetic mutation of these fidelity proteins has also been shown to create a cellular environment that is permissive for the development of tumors, suggesting that these proteins also function as tumor suppressors (TSs). While the first identified TSs were confined to either the nucleus and/or the cytoplasm, it seemed logical to hypothesize that the mitochondria may also contain fidelity proteins that serve as TSs. In this regard, it now appears clear that at least two mitochondrial sirtuins function as sensing, watchdog, or TS proteins in vitro, in vivo, and in human tumor samples. In addition, these new results demonstrate that the mitochondrial anti-aging or fidelity/sensing proteins, SIRT3 and SIRT4, respond to changes in cellular nutrient status to alter the enzymatic activity of specific downstream targets to maintain energy production that matches energy availability and ATP consumption. As such, it is proposed that loss of function or genetic deletion of these mitochondrial genes results in a mismatch of mitochondrial energy metabolism, culminating in a cell phenotype permissive for transformation and tumorigenesis. In addition, these findings clearly suggest that loss of proper mitochondrial metabolism, via loss of SIRT3 and SIRT4, is sufficient to promote carcinogenesis.

Regulation of MnSOD enzymatic activity by Sirt3 connects the mitochondrial acetylome signaling networks to aging and carcinogenesis.

SIGNIFICANCE: It is a well-established scientific observation that mammalian cells contain fidelity or watchdog proteins that maintain the correct function of cellular organelles. RECENT ADVANCES: Over the past several years, the Sirtuin deacetylase family protein Sirt3 has emerged as a mitochondrial fidelity protein that directs energy generation and regulates reactive oxygen species (ROS) scavenging proteins. Loss of function or genetic mutation of these fidelity proteins has been shown to create a cellular environment that is permissive for the development of cellular damage associated with processes such as aging and carcinogenesis. CRITICAL ISSUES: Mitochondria are the primary organelles that direct oxidative metabolism for the production of ATP; however, this is also a significant source of ROS. Thus, it is reasonable to propose that mitochondria should contain proteins that would signal downstream target molecules and/or ROS scavenger enzymes to maintain mitochondrial and cellular homeostatic poise. It is also reasonable to hypothesize that the mitochondria contain fidelity proteins similar to those found in the nucleus and cytoplasm. We discuss a new role of Sirt3 in the direction of the primary superoxide scavenger protein, manganese superoxide dismutase (MnSOD), and how the acetylation or deacetylation of several specific lysines appears to direct MnSOD enzymatic dismutase activity. FUTURE DIRECTIONS: Aberrant downstream regulation of MnSOD by Sirt3 may be a potential source of cellular damage that accumulates with aging to create a tumor-permissive phenotype. Future studies can explore the role of MnSOD in age-related illness using this new mechanism of enzymatic regulation.

Metabolic regulation of Sirtuins upon fasting and the implication for cancer.

PURPOSE OF REVIEW: The purpose of this review is to highlight recent studies on mammalian sirtuins that coordinately regulate cellular metabolic homeostasis upon fasting and to summarize the beneficial effects of fasting on carcinogenesis and cancer therapy. RECENT FINDINGS: Recent studies have demonstrated that fasting may protect normal cells and mice from the metabolic conditions that are harmful as well as decrease the incidence of carcinogenesis. Fasting could also slow the tumor growth and augment the efficacy of certain systemic agents/chemotherapy drugs in various cancers. The mechanism behind this proposed idea may be due to, at least in some part, the metabolic regulation by Sirtuin family proteins whose functions are involved in specific aspects of longevity, stress response and metabolism. Sirtuins, particularly SIRT1 and SIRT3, can be activated by fasting and further exhibit their effects in insulin response, antioxidant defense, and glycolysis. Therefore, sirtuins may have anticancer effects by shifting metabolism to a less proliferative cell phenotype as well as less prone to oxidative stress attack. SUMMARY: The in-depth understanding of the essential role of sirtuins in fasting process may have significant implications in developing a new metabolic diagram of cancer prevention or treatment.

Bicyclo[3.2.0]heptane mechanophores for the non-scissile and photochemically reversible generation of reactive bis-enones.

Force-induced transformations of polymer-bound functionalities have the potential to produce a rich array of stress-responsive behavior. One area of particular interest is the activation of non-scissile mechanophores in which latent reactivity can be unveiled that, under the appropriate conditions, could lead to constructive bond formation in materials exposed to typically destructive stress. Here, the mechanical activation of a bicyclo[3.2.0]heptane (BCH) mechanophore is demonstrated via selective labeling of bis-enone products. BCH ring-opening produces large local elongation (>4 Å) and products that are reactive to conjugate additions under mild conditions. Subsequent photocyclization regenerates the initial BCH functionality, providing switchable structure and reactivity along the polymer backbone in response to stress and visible light.