Design Principles for Perfect Adaptation in Biological Networks with Nonlinear Dynamics.

Establishing a mapping between the emergent biological properties and the repository of network structures has been of great relevance in systems and synthetic biology. Adaptation is one such biological property of paramount importance that promotes regulation in the presence of environmental disturbances. This paper presents a nonlinear systems theory-driven framework to identify the design principles for perfect adaptation with respect to external disturbances of arbitrary magnitude. Based on the prior information about the network, we frame precise mathematical conditions for adaptation using nonlinear systems theory. We first deduce the mathematical conditions for perfect adaptation for constant input disturbances. Subsequently, we translate these conditions to specific necessary structural requirements for adaptation in networks of small size and then extend to argue that there exist only two classes of architectures for a network of any size that can provide local adaptation in the entire state space, namely, incoherent feed-forward (IFF) structure and negative feedback loop with buffer node (NFB). The additional positiveness constraints further narrow the admissible set of network structures. This also aids in establishing the global asymptotic stability for the steady state given a constant input disturbance. The proposed method does not assume any explicit knowledge of the underlying rate kinetics, barring some minimal assumptions. Finally, we also discuss the infeasibility of certain IFF networks in providing adaptation in the presence of downstream connections. Moreover, we propose a generic and novel algorithm based on non-linear systems theory to unravel the design principles for global adaptation. Detailed and extensive simulation studies corroborate the theoretical findings.

The Recent Use, Patient Satisfaction, and Advancement in Digital Smile Designing: A Systematic Review.

Digital smile designing (DSD) is a concept of dentistry which combines the old and the new and becomes a different world in the world of smile aesthetics and functionality. Dental aesthetics is not just a cosmetic issue but a multidimensional part of oral health that has a great impact on psychological well-being, social life, functional capabilities, and, hence, the quality of life. To put it simply, the recognition of its significance stresses the necessity of complete dental care which is the one that combines beauty and function as well as health. This systematic review aims to analyze the recent use and patient satisfaction of DSD and to show the recent advances in DSD. A thorough literature search was conducted across the online databases for articles about the implementation of digital smile analysis in dentistry. The articles that were published between 2013 and 2023 on DSD were selected which included randomized and non-randomized trials and observational studies covering the effectiveness, advantages, and patients' opinions about the treatment. The National Institutes of Health tool was applied for bias assessment. Ten studies were selected to address the use of DSD in dentistry based on the inclusion criteria. The findings from these studies suggest that DSD is useful in improving communication, reducing working time, minimizing errors, enhancing patient satisfaction, and providing clinical adequacy for final prosthetic pieces, indicating the usefulness of this approach in dental procedures. Smile designing using digital technologies has the potential to improve dental aesthetics and treatment procedures while showcasing their reliability and clinical effectiveness.

Coenzyme Q10 supplementation affects cellular ionic balance: relevance to aging.

Aging results into disruptive physiological functioning and cellular processes that affect the composition and structure of the plasma membrane. The plasma membrane is the major regulator of ionic homeostasis that regulates the functioning of membrane transporters and exchangers. Coenzyme Q10 is a lipid-soluble antioxidant molecule that declines during aging and age-associated diseases. The present study aims to explore the role of Coenzyme Q10 supplementation to rats during aging on membrane transporters and redox biomarkers. The study was conducted on young and old male Wistar rats supplemented with 20 mg/kg b.w. of Coenzyme Q10 per day. After a period of 28 days, rats were sacrificed and erythrocyte membrane was isolated. The result exhibits significant decline in biomarkers of oxidative stress in old control rats when compared with young control. The effect of Coenzyme Q10 supplementation was more pronounced in old rats. The functioning of membrane transporters and Na+/H+ exchanger showed potential return to normal levels in the Coenzyme Q10 treated rats. Overall, the results demonstrate that Coenzyme Q10 plays an important role in maintaining redox balance in cells which interconnects with membrane integrity. Thus, Coenzyme Q10 supplementation may play an important role in protecting age related alterations in erythrocyte membrane physiology.

BACE1 inhibitor drugs for the treatment of Alzheimer's disease: Lessons learned, challenges to overcome, and future prospects†.

Alzheimer's disease (AD), first diagnosed over a century ago, remains one of the major healthcare crises around the globe. Currently, there is no cure or effective treatment. The majority of drug development efforts to date have targeted reduction of amyloid-ß peptide (Aß). Drug development through inhibition of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), resulted in promising early clinical studies. However, nearly all small molecule BACE1 inhibitor drugs failed to live up to expectations in later phase clinical trials, due to toxicity and efficacy issues. This commentary aims to provide a brief review of over two decades of BACE1 inhibitor drug development challenges and efforts for treatment of AD and prospects of future BACE1-based drugs.

Validating the temporal performance of genetic biomarkers in an animal model of recurrence/ non-recurrence myocardial infarction persuades by bioinformatics tools.

With a global towering prevalence of index acute myocardial infarction (nonrecurrent MI, NR-MI), a high incidence of recurrent MI (R-MI) has emerged in recent decades. Despite the extensive occurrence, the promising predictors of R-MI have been elusive within the cohort of survivors. This study investigates and validates the involvement of distinct gene expressions in R-MI and NR-MI. Bioinformatics tools were used to identify DEGs from the GEO dataset, functional annotation, pathway enrichment analysis, and the PPI network analysis to find hub genes. The validation of proposed genes was conceded by qRT-PCR and Western Blot analysis in experimentally induced NR-MI and R-MI models on a temporal basis. The temporal findings based on RT-PCR consequences reveal a significant and constant upregulation of the UBE2N in the NR-MI model out of the proposed three DEGs (UBE2N, UBB, and TMEM189), while no expression was reported in the R-MI model. Additionally, the proteomics study proposed five DEGs (IL2RB, NKG7, GZMH, CXCR6, and GZMK) for the R-MI model since IL2RB was spotted for significant and persistent downregulation with different time points. Further, Western Blot analysis validated these target genes' expressions temporally. I/R-induced NR-MI and R-MI models were confirmed by the biochemical parameters (CKMB, LDH, cTnI, serum nitrite/nitrate concentration, and inflammatory cytokines) and histological assessments of myocardial tissue. These results underscore the importance of understanding genetic mechanisms underlying MI and highlight the potential of UBE2N and IL2RB as biomarkers for non-recurrent and recurrent MI, respectively.

Comprehensive study on pharmacognostic, pharmacological, and toxicological features of Ficus racemosa in Alzheimer's disease using GC-MS and molecular docking analyses.

Background: Alzheimer's disease (AD) presents as a widespread neurodegenerative condition impacting over 55 million individuals globally, with an annual rise of 10 million new cases. Despite its staggering prevalence, the absence of a definitive cure establishes the need for a revisit. Methods: We explore the alternative strategies, focusing on the potential therapeutic efficacy of ethanolic extracts derived from the fruit and leaf of Ficus racemosa Linn. Results: The investigation comprehensively explores pharmacognostic, phytochemical, toxicological, and pharmacological characteristics. In addition to pharmacognostic and physicochemical analyses, toxicological evaluations conducted on experimental animals demonstrated the innocuous nature of the ethanolic extracts (from both fruit and leaf) of F. racemosa, as evidenced by assessments of hemocompatibility, oxidative parameters, and vital organ histology. Phytochemical profiling via GC-MS identified 48 and 80 phytoconstituents in the fruit and leaf extracts, respectively. These constituents were screened for bioactive potential using the "Lipinski Rule of Five," resulting in the selection of 25 and 33 constituents from fruit and leaf extracts, respectively. Subsequent molecular docking studies against the AChE enzyme revealed promising interactions of the selected phytoconstituents. Furthermore, the top-scoring phytoconstituents were subjected to in silico screening to assess their interactions with ß- and γ-secretase enzymes, in addition to the AChE enzyme. The cumulative findings substantiate the therapeutic utility of the plant extracts, particularly in the context of AD. Conclusion: In conclusion, our investigation highlights the promising therapeutic potential of selected phytoconstituents derived from ethanolic extracts of F. racemosa in mitigating AD pathology by targeting key enzyme sites such as AChE, ß-, and γ-secretase.

Evaluation of Meibomian Gland Structure and Function in Patients with Vernal Keratoconjunctivitis Using Non Contact Meibography and Lipid Layer Interferometry.

PURPOSE: This study evaluated the structural and functional impact of vernal keratoconjunctivitis (VKC) on meibomian glands (MGs) using a combination of noncontact meibography and lipid layer interferometry. METHODS: In this observational study 50 patients with moderate persistent or severe VKC and 50 age-matched controls underwent MG imaging and lipid layer thickness (LLT) measurements with Lipiview II. Image J software was used to assess MG loss (meibograde) in both lids. All patients underwent dry eye evaluation comprising tear break-up time (TBUT), ocular surface staining (OSS), Schirmer I scoring, and meiboscoring (expressibility and quality of meibum secreted). RESULTS: Meibograde, OSS score, and meiboscore was higher in cases (2.68 ± 0.96, 0.580 ± 1.07, and 0.56 ± 0.95 respectively) than controls (1.80 ± 0.67, 0.00 ± 0.00, 0.22 ± 0.47 respectively) (p < 0.001, 0.001, 0.025 respectively). LLT and TBUT was lower in cases (54.58 ± 9.43 nm and 4.92 ± 3.09 sec respectively) than controls (70.14 ± 22.50 nm and 12.02 ± 2.73 sec respectively) (both p's = 0.001). Both groups had comparable Schirmer I scores. CONCLUSION: Children with VKC have significant MG dropouts, deterioration in meibum quality and a thinner and less stable tear film. VKC patients are thus prone to a vicious cycle of inflammation attributable both to the allergic component and to deterioration in MG structure and function. Co-management of MG dysfunction warrants as much attention as the allergic component itself.

Identification of Novel Isatin Derivative Bearing a Nitrofuran Moiety as Potent Multi-Isoform Aldehyde Dehydrogenase Inhibitor.

Aldehyde dehydrogenases (ALDHs) are a family of enzymes that aid in detoxification and are overexpressed in several different malignancies. There is a correlation between increased expression of ALDH and a poor prognosis, stemness, and resistance to several drugs. Several ALDH inhibitors have been generated due to the crucial role that ALDH plays in cancer stem cells. All of these inhibitors, however, are either ineffective, very toxic, or have yet to be subjected to rigorous testing on their effectiveness. Although various drug-like compounds targeting ALDH have been reported in the literature, none have made it to routine use in the oncology clinic. As a result, new potent, non-toxic, bioavailable, and therapeutically effective ALDH inhibitors are still needed. In this study, we designed and synthesized potent multi-ALDH isoform inhibitors based on the isatin and indazole pharmacophore. Molecular docking studies and enzymatic tests revealed that among all of the synthesized analogs, compound 3 is the most potent inhibitor of ALDH1A1, ALDH3A1, and ALDH1A3, exhibiting 51.32%, 51.87%, and 36.65% inhibition, respectively. The ALDEFLUOR assay further revealed that compound 3 acts as an ALDH broad spectrum inhibitor at 500 nM. Compound 3 was also the most cytotoxic to cancer cells, with an IC50 in the range of 2.1 to 3.8 µM for ovarian, colon, and pancreatic cancer cells, compared to normal and embryonic kidney cells (IC50 7.1 to 8.7 µM). Mechanistically, compound 3 increased ROS activity due to potent multi-ALDH isoform inhibition, which increased apoptosis. Taken together, this study identified a potent multi-isoform ALDH inhibitor that could be further developed as a cancer therapeutic.

Diagnosis and Dental Management of a Patient With Forbes Albright Syndrome: A Report of a Rare Case.

Forbes Albright syndrome is a hyperprolactinemia syndrome linked to a pituitary tumor associated with galactorrhea and amenorrhea. Cabergoline, an ergot derivative, is its drug of choice. Here, we report the oral manifestations and management of a case of a 32-year-old female, diagnosed and treated with the same. The patient had an alarming increase in the incidence and progression of dental caries. Her diagnosis and management have been highlighted. This can have overbearing effects on the psychology and function of the individual, thus making early diagnosis and precise management important.

COVLIAS 3.0: cloud-based quantized hybrid UNet3+ deep learning for COVID-19 lesion detection in lung computed tomography.

Background and novelty: When RT-PCR is ineffective in early diagnosis and understanding of COVID-19 severity, Computed Tomography (CT) scans are needed for COVID diagnosis, especially in patients having high ground-glass opacities, consolidations, and crazy paving. Radiologists find the manual method for lesion detection in CT very challenging and tedious. Previously solo deep learning (SDL) was tried but they had low to moderate-level performance. This study presents two new cloud-based quantized deep learning UNet3+ hybrid (HDL) models, which incorporated full-scale skip connections to enhance and improve the detections. Methodology: Annotations from expert radiologists were used to train one SDL (UNet3+), and two HDL models, namely, VGG-UNet3+ and ResNet-UNet3+. For accuracy, 5-fold cross-validation protocols, training on 3,500 CT scans, and testing on unseen 500 CT scans were adopted in the cloud framework. Two kinds of loss functions were used: Dice Similarity (DS) and binary cross-entropy (BCE). Performance was evaluated using (i) Area error, (ii) DS, (iii) Jaccard Index, (iii) Bland-Altman, and (iv) Correlation plots. Results: Among the two HDL models, ResNet-UNet3+ was superior to UNet3+ by 17 and 10% for Dice and BCE loss. The models were further compressed using quantization showing a percentage size reduction of 66.76, 36.64, and 46.23%, respectively, for UNet3+, VGG-UNet3+, and ResNet-UNet3+. Its stability and reliability were proved by statistical tests such as the Mann-Whitney, Paired t-Test, Wilcoxon test, and Friedman test all of which had a p < 0.001. Conclusion: Full-scale skip connections of UNet3+ with VGG and ResNet in HDL framework proved the hypothesis showing powerful results improving the detection accuracy of COVID-19.

Exploring Novel Coumarin-Tethered Bis-Triazoles: Apoptosis Induction in Human Pancreatic Cancer Cells, Antimicrobial Effects, and Molecular modelling Investigations.

In the present study, we identified that two representative compounds (7c and 9f) of our newly synthesized coumarin-tagged bis-triazoles induced apoptosis in human pancreatic cells (PANC-1) by caspase 3/7mediated pathway. Both 7c and 9f (IC50 = 7.15 ± 1.19 and 6.09 ± 0.79 µM, respectively) were found to be ~100 times superior against PANC-1 as compared to the standard drug Gemcitabine (IC50 = >500 µM), without showing any toxicity to the normal pancreatic epithelial cells (H6C7). Molecular docking studies further endorsed them as potential pancreatic cancer therapeutics due to their strong hydrogen bonding interactions with the epidermal growth factor receptor (EGFR) enzyme, which is overexpressed in cancerous cells including pancreatic cancer. Additionally, these compounds also showed moderate inhibitory activity against a panel of microbial strains. Overall, our findings reveal that the coumarin hybrids 7c and 9f are viable chemotypes to be adopted as templates for the development of new anticancer drugs, particularly against pancreatic cancer.

Lignin nanoparticles from Ayurvedic industry spent materials: Applications in Pickering emulsions for curcumin and vitamin D3 encapsulation.

Lignin nanoparticles (LNP), extracted from spent materials of Dashamoola Arishta (Ayurvedic formulation), shared a molecular weight of 14.42 kDa with commercial lignin. Processed into LNPs (496.43 ± 0.54 nm) via planetary ball milling, they demonstrated stability at pH 8.0 with a zeta potential of -32 ± 0.27 mV. Operating as Pickering particles, LNP encapsulated curcumin and vitamin D3 in sunflower oil, forming LnE + Cu + vD3 nanoemulsions (particle size: 347.40 ± 0.71 nm, zeta potential: -42.27 ± 0.72 mV) with high encapsulation efficiencies (curcumin: 87.95 ± 0.21%, vitamin D3: 72.66 ± 0.11%). The LnE + Cu + vD3 emulsion exhibited stability without phase separation over 90 days at room (27 ± 2 °C) and refrigeration (4 ± 1 °C) temperatures. Remarkably, LnE + Cu + vD3 exhibited reduced toxicity, causing 29.32% and 34.99% cell death in L6 and RAW264.7 cells respectively, at the highest concentration (50 µg/mL). This underscores the potential valorization of Ayurvedic industry spent materials for diverse industrial applications.

Sarcopenia in gastric cancer and its impact on early postoperative outcome.

BACKGROUND: Sarcopenia, defined as progressive and generalised loss of skeletal muscle mass, quality, and strength, is considered as a poor prognostic factor in cancer. Outcomes in oncology mainly focus on survival related to disease and treatment. Other factors affecting the end result get less attention. This study was conducted with the aim to determine presence of sarcopenia in operable gastric cancer, factors positively correlating with presence of sarcopenia and its impact on early postoperative outcomes. METHODOLOGY: This is a prospective study conducted from January 2020 to December 2021 in a tertiary care cancer hospital. All patients with adenocarcinoma stomach planned for curative intent surgery were assessed for sarcopenia by measuring hand grip strength(HGS) and skeletal muscle index(SMI). Comparison was made between patient and tumour related factors in patients with and without sarcopenia and impact of sarcopenia on early postoperative outcome was assessed. RESULTS: 74 patients were assessed for sarcopenia. 32 (43.2 %) were patients diagnosed with sarcopenia. Advanced age(p = 0.040), low BMI (p < 0.001), gastric outlet obstruction (p = 0.020) and urgent surgery (p = 0.002) positively correlated with sarcopenia. Curative resection was done in 68(91.89 %) patients and these patients were evaluated for early postoperative outcomes. 18 (26.5 %) patients had complications of Clavien Dindo grade 3 or above. Sarcopenia was not significantly associated with major postoperative complications(p = 0.857). CONCLUSION: Sarcopenia, though associated with a substantial proportion of patients with gastric cancer, does not significantly affect early postoperative complications in a high volume oncology centre .

Evaluating therapeutic potential of NR2E3 doses in the rd7 mouse model of retinal degeneration.

Retinitis Pigmentosa is a leading cause of severe vision loss. Retinitis Pigmentosa can present with a broad range of phenotypes impacted by disease age of onset, severity, and progression. This variation is influenced both by different gene mutations as well as unique variants within the same gene. Mutations in the nuclear hormone receptor 2 family e, member 3 are associated with several forms of retinal degeneration, including Retinitis Pigmentosa. In our previous studies we demonstrated that subretinal administration of one Nr2e3 dose attenuated retinal degeneration in rd7 mice for at least 3 months. Here we expand the studies to evaluate the efficacy and longitudinal impact of the NR2E3 therapeutic by examining three different doses administered at early or intermediate stages of retinal degeneration in the rd7 mice. Our study revealed retinal morphology was significantly improved 6 months post for all doses in the early-stage treatment groups and for the low and mid doses in the intermediate stage treatment groups. Similarly, photoreceptor function was significantly improved in the early stage for all doses and intermediate stage low and mid dose groups 6 months post treatment. This study demonstrated efficacy in multiple doses of NR2E3 therapy.

Identification of a Novel Protein Phosphatase 2A Activator, PPA24, as a Potential Therapeutic for FOLFOX-Resistant Colorectal Cancer.

A series of compounds were designed utilizing molecular modeling and fragment-based design based upon the known protein phosphatase 2A (PP2A) activators, NSC49L and iHAP1, and evaluated for their ability to inhibit the viability of colorectal cancer (CRC) and folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX)-resistant CRC cells. PPA24 (19a) was identified as the most cytotoxic compound with IC50 values in the range of 2.36-6.75 µM in CRC and FOLFOX-resistant CRC cell lines. It stimulated PP2A activity to a greater extent, displayed lower binding energies through molecular docking, and showed higher binding affinity through surface plasmon resonance for PP2A catalytic subunit α than the known PP2A activators. PPA24 dose-dependently induced apoptosis and oxidative stress, decreased the level of c-Myc expression, and synergistically potentiated cytotoxicity when combined with gemcitabine and cisplatin. Furthermore, a PPA24-encapsulated nanoformulation significantly inhibited the growth of CRC xenografts without systemic toxicities. Together, these results signify the potential of PPA24 as a novel PP2A activator and a prospective therapeutic for CRC and FOLFOX-resistant CRC.

Investigating the impact of milk protein, inulin, and honey on quality attributes of goat milk yoghurt.

In this present study, a three-factor Box-Behnken, response surface methodology (RSM) design was employed to optimize the skimmed milk powder (SMP)/whey protein concentrate (WPC) ratio (0.25-0.75%w/v) as a source of milk protein, inulin (1-2%w/v), and honey (4-6%w/v) for production of high-quality goat milk yoghurt (GMY). The resulting ANOVA and response surface equations revealed the significant effect (p < 0.05) of these variables on the various attributes such as total solid (%), pH, titratable acidity [(LA) % by weight], syneresis (%), DPPH (% inhibition), viscosity (m.Pa⋅s), whiteness index (WI), and overall acceptability (OA). The coefficient of determination (R2) for all response variables ranged from 0.88 to 0.99. Lack-of-fit tests resulted in non-significant F-values. The optimal conditions were determined as SMP/WPC at 0.36%w/v, inulin at 1.00%w/v, and honey at 6.00%w/v. The optimum values for total solid, pH, titratable acidity, syneresis, DPPH, viscosity, WI, and OA were 22.03, 4.46, 0.77, 6.34, 25.20, 182.30, 76.29 and 8.37, respectively with desirability value of 0.95.

Design of substituted tetrahydrofuran derivatives for HIV-1 protease inhibitors: synthesis, biological evaluation, and X-ray structural studies.

Substituted tetrahydrofuran derivatives were designed and synthesized to serve as the P2 ligand for a series of potent HIV-1 protease inhibitors. Both enantiomers of the tetrahydrofuran derivatives were synthesized stereoselectivity in optically active forms using lipase-PS catalyzed enzymatic resolution as the key step. These tetrahydrofuran derivatives are designed to promote hydrogen bonding and van der Waals interactions with the backbone atoms in the S2 subsite of the HIV-1 protease active site. Several inhibitors displayed very potent HIV-1 protease inhibitory activity. A high-resolution X-ray crystal structure of an inhibitor-bound HIV-1 protease provided important insight into the ligand binding site interactions in the active site.

AngioVac Procedures: Integration of cardiac surgeon and anesthesiologist-led transesophageal echocardiography: A preliminary report.

Introduction: The AngioVac system is a novel, minimally invasive, endovascular technique used to evacuate intravascular or intracardiac vegetation or thrombus. Although most AngioVac procedures are currently performed by interventionalists, this innovative procedure has been gaining attention among the surgical and anesthesia communities. Methods: We retrospectively reviewed all patients who underwent the AngioVac procedure performed by a cardiac surgeon between August 2019 and December 2022. Fellowship-trained cardiac anesthesiologists operated TEE to navigate the AngioVac cannula during the procedure. The stored TEE images were retrospectively reviewed and independently analyzed by two cardiac anesthesiologists with specific focus on TEE-guided navigation of the AngioVac cannula towards the aspiration target. Results: Eleven patients underwent the AngioVac procedure during the study period. In nine cases, the majority of the vegetation or thrombus was successfully aspirated. In two cases, incomplete aspiration was attributed to the mass burden being too large, firm, and chronic in etiology. Worsening tricuspid regurgitation (TR) was identified in three of the 11 cases. Intraoperative TEE provided the cardiac surgeon with simultaneous display of the AngioVac cannula shaft, its tip, and aspiration target, as well as real-time assessment of TR, facilitating the minute movements essential for successful outcomes. Conclusions: This study details our experience and the effectiveness of the AngioVac system for treating soft, intracardiac vegetation or thrombus in a minimally invasive manner. Experienced cardiac anesthesiologists have the skillsets and knowledge to provide optimal live TEE imaging necessary for successful maneuvering of the AngioVac cannula.

Proteomic profiling of regenerated urinary bladder tissue in a non-human primate augmentation model.

Urinary bladder dysfunction can be caused by environmental, genetic, and developmental insults. Depending upon insult severity, the bladder may lose its ability to maintain volumetric capacity and intravesical pressure resulting in renal deterioration. Bladder augmentation enterocystoplasty (BAE) is utilized to increase bladder capacity to preserve renal function using autologous bowel tissue as a "patch." To avoid the clinical complications associated with this procedure, we have engineered composite grafts comprised of autologous bone marrow mesenchymal stem cells (MSCs) co-seeded with CD34+ hematopoietic stem/progenitor cells (HSPCs) onto a pliable synthetic scaffold [poly(1,8-octamethylene-citrate-co-octanol)(POCO)] or a biological scaffold (SIS; small intestinal submucosa) to regenerate bladder tissue in our baboon bladder augmentation model. We set out to determine the global protein expression profile of bladder tissue that has undergone regeneration with the aforementioned stem cell seeded scaffolds along with baboons that underwent BAE. Data demonstrate that POCO and SIS grafted animals share high protein homogeneity between native and regenerated tissues while BAE animals displayed heterogeneous protein expression between the tissues following long-term engraftment. We posit that stem cell-seeded scaffolds can recapitulate tissue that is nearly indistinguishable from native tissue at the protein level and may be used in lieu of procedures such as BAE.