Effects of orthokeratology on corneal reshaping and the delaying of axial eye growth in children.

Purpose: To investigate the inhibition of myopia progression and axial elongation in children wearing orthokeratology (OK) lenses, as well as to evaluate the status of corneal reshaping, this study explores the relationship between changes in central corneal curvature (K-value) and e-value induced by OK lenses and axial elongation. Methods: In this study, it is planned to select children aged 8-15 who wear orthokeratology lenses at the Pediatric Ophthalmology and Strabismus Clinic of the Second Affiliated Hospital of Dalian Medical University. All children will undergo slit lamp examination, visual acuity assessment, computerized refraction, intraocular pressure measurement, biometry, and corneal topography examination before lens wear and at 1 month, 3 months, and 6 months after lens wear in the pediatric ophthalmology clinic. Based on age (lower age group (8 < age ≤12 years); higher age group (12 < age ≤15 years)) and baseline equivalent spherical (SE) value (mild myopia group (-1.00 D < SE ≤ -3.25D); moderate myopia group (-3.25 D < SE ≤ -6.00 D)), four groups will be formed by pairing these factors. Suitable data will be selected according to inclusion and exclusion criteria, and different groups will be included. Data will be organized, and statistical analysis will be performed using SPSS software to obtain the results. The expected results will be discussed and analyzed. Results: After wearing OK lenses, all four groups achieved good visual acuity at follow-up. At 6 months, there were no significant differences in visual acuity among the four groups (P = 0.149, >0.05). There were no significant differences in refractive error among the four groups (P = 0.066, >0.05). Baseline axial length differed significantly among the four groups (P = 0.000, <0.001), with the LM group having longer axial length than the LL group (P < 0.001, paired samples t-test), and the HM group having longer axial length than the HL group (P < 0.001, paired samples t-test). However, there were no significant differences in axial length change compared to baseline among the groups at 1 month, 3 months, and 6 months (P 1 = 0.053; P 3 = 0.557; P 6 = 0.329, >0.05). Significant differences were observed in corneal flat K-value change compared to baseline among the four groups at 1 month, 3 months, and 6 months (P 1 = 0.001, P 3 = 0.001, P 6 = 0.004, <0.05). There were no significant differences in e-value change among the groups at 1 and 3 months (P 1 = 0.205, P 3 = 0.252, >0.05), but significant differences were found in e-value change compared to baseline at 6 months (P 6 = 0.010, <0.05). Multiple regression analysis with changes in central corneal flat K-value and e-value as independent variables and axial elongation as the dependent variable showed a correlation between e-value change at 6 months and axial elongation (P = 0.004, <0.05), indicating a negative correlation. Conclusion: Orthokeratology (OK) lenses effectively improve myopic children's vision by reshaping the cornea, leading to reduced central corneal curvature and flattening of its anterior surface. The effectiveness of OK lenses is not significantly affected by age or initial myopia severity. Children of varying ages and myopia levels experience similar levels of axial length control with OK lens wear. Changes in corneal shape due to OK lenses affect axial elongation, with greater changes in corneal morphology associated with smaller increases in axial length.

A Glucose-Responsive Hydrogel Inhibits Primary and Secondary BRB Injury for Retinal Microenvironment Remodeling in Diabetic Retinopathy.

Current diabetic retinopathy (DR) treatment involves blood glucose regulation combined with laser photocoagulation or intravitreal injection of vascular endothelial growth factor (VEGF) antibodies. However, due to the complex pathogenesis and cross-interference of multiple biochemical pathways, these interventions cannot block disease progression. Recognizing the critical role of the retinal microenvironment (RME) in DR, it is hypothesized that reshaping the RME by simultaneously inhibiting primary and secondary blood-retinal barrier (BRB) injury can attenuate DR. For this, a glucose-responsive hydrogel named Cu-PEI/siMyD88@GEMA-Con A (CSGC) is developed that effectively delivers Cu-PEI/siMyD88 nanoparticles (NPs) to the retinal pigment epithelium (RPE). The Cu-PEI NPs act as antioxidant enzymes, scavenging ROS and inhibiting RPE pyroptosis, ultimately blocking primary BRB injury by reducing microglial activation and Th1 differentiation. Simultaneously, MyD88 expression silence in combination with the Cu-PEI NPs decreases IL-18 production, synergistically reduces VEGF levels, and enhances tight junction proteins expression, thus blocking secondary BRB injury. In summary, via remodeling the RME, the CSGC hydrogel has the potential to disrupt the detrimental cycle of cross-interference between primary and secondary BRB injury, providing a promising therapeutic strategy for DR.

The Use of Cross-Linked Hyaluronic Acid in Non-surgical Rhinoplasty Using Italian Technique.

INTRODUCTION: Projection and upper rotation to the tip is fundamental in the nasal rejuvenation, as a matter of fact the tip is the most important and has strongly effects on the improve appearance and quality of life. The aim of the present study was to evaluate reshaping the tip of the nose by cross-linked hyaluronic acid using Italian technique. METHODS: In a period between November 2019 and 2023, a total of one hundred and forty healthy, 95 females and 45 man patients, were performed with a mean age 44±5 (age range: 31-52 years old) affected by tip of congenital (22) or ageing nose hypotonia (118), and reduced volume that need of an elevation of the nose tip. The anatomic markers have been considered for the anthropometric measurements after the filler rhinoplasty. Two infiltrations were performed, one in the infiltration into the antero-caudal access over the columella produce upward rotation of the tip of the nose and second infiltration into the antero-superior access produce the projection of the tip of the nose. Medical device used in the study was Neofound STRUCT LIDO (LOVE COSMEDICAL srls-Via Toniolo 9, 57022 Castagneto Carducci, ITALY) containing sodium hyaluronate/hyaluronic acid high molecular weight (1.500

Microinjection Technique: A Novel and Comprehensive Approach for Nose Reshaping with Hyaluronic Acid Fillers.

Introduction: Nose reshaping with hyaluronic acid (HA) fillers, also known as medical rhinoplasty, is an increasingly popular, minimally invasive aesthetic procedure. As the demand for nasal reshaping continues to rise, it is essential to develop safe and efficient injection techniques and assess satisfaction to ensure optimal outcomes and patient-centered care. Objective: This study aims to evaluate patient and physician satisfaction with hyaluronic acid filler applications using microinjection technique for nasal reshaping. Methods: The study included healthy adult patients who underwent medical rhinoplasty with the same HA filler using the microinjection technique. Patient satisfaction levels were evaluated at one and six months after the last injection using the Global Patient Satisfaction Scale (GPSS). Additionally, an independent dermatologist conducted a clinical evaluation for each patient by comparing before and after clinical pictures, using the Aesthetic Improvement Scale (AIS). Any side effects were recorded during each session and follow-up period for six months. Results: A total of 40 patients (37 women and 3 men) participated in the study. The most frequently targeted anatomical areas for filler injections were the nasal tip (100%), columella (100%), nasal prominence (100%), nasal dorsum (85%), and nasal root (82.5%). Injections distal to the nasolabial fold (NFL) were performed in 2.5 percent of patients. Patients expressed high satisfaction with the results at both one and six months after the procedure (mean GPSS, respectively; 4.65 and 4.47). Similarly, clinicians reported satisfaction with outcomes at the same time points (mean AIS, respectively; 1.7 and 1.4). Apart from mild pain during the procedure and transient erythema afterward, no side effects were recorded. Conclusion: Medical rhinoplasty with HA fillers using the microinjection technique is an effective and reliable procedure. This technique provides safe and aesthetically pleasing results from both patient and dermatologist perspectives, making it a favorable option for nasal reshaping with HA dermal fillers.

Enhanced pyroptosis induction with pore-forming gene delivery for osteosarcoma microenvironment reshaping.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

Effects of adherence to treatment for repositioning therapy, physical therapy, and cranial remolding orthoses in infants with cranial deformation.

Deformational head shapes are most often treated through repositioning therapy (RT) and/or cranial remolding orthotic (CRO) treatment. However, there is conflicting evidence about the effectiveness of each method, and treatment compliance is suspected to affect treatment effectiveness. This study examines participant adherence with these treatment methods and explores if cranial correction is related to compliance. This study also reviews effects of developmental milestones and explores other potential impacts on compliance. A total of 45 infants with cranial deformation were consented and those with congenital muscular torticollis (CMT) concurrently received physical therapy. Infants were followed from 2 to 12 months of age and initially assigned to RT. Caregivers continued RT until the head shape corrected, caregivers chose to switch to a CRO, or infants turned 12 months of age. All participants were scheduled for a final visit at 12 months of age. Throughout treatment, caregiver surveys were used to examine compliance and developmental milestones. Results show promise for future investigation into the relationship between treatment modalities and adherence with treatment for deformational head shapes. Our findings provide preliminary support that treatment adherence may be linked with treatment success and concurrent enrollment in physical therapy increases patient compliance.

Turn Your Vision into Reality-AI-Powered Pre-operative Outcome Simulation in Rhinoplasty Surgery.

BACKGROUND: The increasing demand and changing trends in rhinoplasty surgery emphasize the need for effective doctor-patient communication, for which Artificial Intelligence (AI) could be a valuable tool in managing patient expectations during pre-operative consultations. OBJECTIVE: To develop an AI-based model to simulate realistic postoperative rhinoplasty outcomes. METHODS: We trained a Generative Adversarial Network (GAN) using 3,030 rhinoplasty patients' pre- and postoperative images. One-hundred-one study participants were presented with 30 pre-rhinoplasty patient photographs followed by an image set consisting of the real postoperative versus the GAN-generated image and asked to identify the GAN-generated image. RESULTS: The study sample (48 males, 53 females, mean age of 31.6 ± 9.0 years) correctly identified the GAN-generated images with an accuracy of 52.5 ± 14.3%. Male study participants were more likely to identify the AI-generated images compared with female study participants (55.4% versus 49.6%; p = 0.042). CONCLUSION: We presented a GAN-based simulator for rhinoplasty outcomes which used pre-operative patient images to predict accurate representations that were not perceived as different from real postoperative outcomes. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

First national analysis of severe obesity hospitalizations in Italy: insights from discharge card database.

Background: Obesity is associated with numerous severe diseases necessitating intensive healthcare for diagnosis and treatment. Most patients with obesity, especially in its severe form, require at least one hospitalization. However, few studies in Italy have assessed the burden of obesity on the National Health System. This study aims to routinely estimate the 'disease burden' by analyzing hospital admissions related to severe obesity. Subjects: We analyzed the medical records of the Italian national hospital discharge database, including all patients older than 18 years discharged with the diagnosis of 'severe obesity'.' We included patients who underwent bariatric surgery, even without an explicit obesity code, such as laparoscopic restrictive gastric procedures, other stomach operations, and high gastric bypass. Special focus was given to those who underwent abdominal reshaping surgery. The cross-sectional survey PASSI in Italy served as an additional data source to estimate. The phenomenon was described using appropriate indicators, including rates and ratios between rates. Linear regression was employed to analyze trends in standardized rates over time. Results: Between 2014 and 2021, a total of 243,325 patients were discharged with a severe obesity code in Italy. Among these patients, 36.8% underwent at least one bariatric surgery procedure. We investigated the types of bariatric surgery procedures performed. The most frequent procedure was "other operations on the stomach," where sleeve gastrectomy is included which also appears to be steadily increasing during the study period together with the gastric bypass, while the gastric bondage is decreasing over time. Conclusion: These findings underscore the significant burden of severe obesity on Italy's healthcare system, a burden that is progressively increasing. The growing utilization of bariatric surgery suggests an escalating trend toward adopting drastic solutions to combat this health issue.

Diverse models of cavity engineering in enzyme modification: Creation, filling, and reshaping.

Most enzyme modification strategies focus on designing the active sites or their surrounding structures. Interestingly, a large portion of the enzymes (60%) feature active sites located within spacious cavities. Despite recent discoveries, cavity-mediated enzyme engineering remains crucial for enhancing enzyme properties and unraveling folding-unfolding mechanisms. Cavity engineering influences enzyme stability, catalytic activity, specificity, substrate recognition, and docking. This article provides a comprehensive review of various cavity engineering models for enzyme modification, including cavity creation, filling, and reshaping. Additionally, it also discusses feasible tools for geometric analysis, functional assessment, and modification of cavities, and explores potential future research directions in this field. Furthermore, a promising universal modification strategy for cavity engineering that leverages state-of-the-art technologies and methodologies to tailor cavities according to the specific requirements of industrial production conditions is proposed.

Role of adhesion molecules in cancer and targeted therapy.

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them. Various mechanisms deregulate adhesion molecules in cancer, enabling tumor cells to proliferate without restraint, invade through tissue boundaries, escape from immune surveillance, and survive in the tumor microenvironment. Recent studies have revealed that adhesion molecules also drive angiogenesis, reshape metabolism, and are involved in stem cell self-renewal. In this review, we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment, as well as the therapeutic strategies targeting adhesion molecules. These studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.

Lymphoma dissemination is a pathological hallmark for malignant progression of B-cell lymphoma.

Extranodal lymphoma occurs in one-third of lymphoma patients and is a key indicator of the international prognostic index, associated with unfavorable outcomes. Due to the lack of ideal models, the causes and characteristics of extranodal lymphoma are greatly underexplored. Recently, we observed a high incidence of extranodal lymphoma in two types of mouse models with tropism for the brain and kidneys. These findings prompt us to rethink the pathological progression of lymphoma colonization in lymph nodes and non-lymphoid organs. Nodal lymphoma, primary extranodal lymphoma and secondary extranodal lymphoma should be biologically and clinically distinctive scenarios. Based on the observations in mouse models with extranodal lymphoma, we propose that lymphoma dissemination can be seen as lymphoma losing the ability to home to lymph nodes. The pathological process of nodal lymphoma should be referred to as lymphoma homing to distinguish it from benign hyperplasia. Lymphoma dissemination, defined as a pathological process that lymphoma can occur in almost any part of the body, is a key pathological hallmark for malignant progression of B-cell lymphoma. Reshaping cellular plasticity is a promising strategy to allow transformed cells to homing back to lymph nodes and re-sensitize tumor cells to treatment. From this perspective, we provide new insights into the pathological progression of lymphoma dissemination and its inspiration on therapeutic interventions. We believe that establishing extranodal lymphoma mouse models, identifying molecular mechanism governing lymphoma dissemination, and developing therapies to prevent lymphoma dissemination will become emerging topics for fighting relapsed and refractory lymphoma.

Reshaping Intratumoral Mononuclear Phagocytes with Antibody-Opsonized Immunometabolic Nanoparticles.

Mononuclear phagocytes (MPs) are vital components of host immune defenses against cancer. However, tumor-infiltrating MPs often present tolerogenic and pro-tumorigenic phenotypes via metabolic switching triggered by excessive lipid accumulation in solid tumors. Inspired by viral infection-mediated MP modulation, here enveloped immunometabolic nanoparticles (immeNPs) are designed to co-deliver a viral RNA analog and a fatty acid oxidation regulator for synergistic reshaping of intratumoral MPs. These immeNPs are camouflaged with cancer cell membranes for tumor homing and opsonized with anti-CD163 antibodies for specific MP recognition and uptake. It is found that internalized immeNPs coordinate lipid metabolic reprogramming with innate immune stimulation, inducing M2-to-M1 macrophage repolarization and tolerogenic-to-immunogenic dendritic cell differentiation for cytotoxic T cell infiltration. The authors further demonstrate that the use of immeNPs confers susceptibility to anti-PD-1 therapy in immune checkpoint blockade-resistant breast and ovarian tumors, and thereby provide a promising strategy to expand the potential of conventional immunotherapy.

Aesthetic Ideals of the Female Buttocks: Concepts and Techniques.

This article explores the importance of understanding the tridimensional artistic anatomy of the back, pelvis, and thighs in gluteal surgery. It emphasizes the need for plastic surgeons to have a comprehensive knowledge of these anatomic structures to achieve successful outcomes. The authors highlight the significance of ethnic differences in determining ideal aesthetic results and stress the importance of considering and respecting these variations. Individualization of treatment is a key principle in gluteal surgery, as each patient has unique preferences and needs. Effective communication and collaboration between the surgeon and the patient are crucial in determining desired aesthetic goals and achieving satisfactory outcomes.

Prime editor-mediated functional reshaping of ACE2 prevents the entry of multiple human coronaviruses, including SARS-CoV-2 variants.

The spike protein of SARS-CoV-2 hijacks the host angiotensin converting enzyme 2 (ACE2) to meditate its entry and is the primary target for vaccine development. Nevertheless, SARS-CoV-2 keeps evolving and the latest Omicron subvariants BQ.1 and XBB have gained exceptional immune evasion potential through mutations in their spike proteins, leading to sharply reduced efficacy of current spike-focused vaccines and therapeutics. Compared with the fast-evolving spike protein, targeting host ACE2 offers an alternative antiviral strategy that is more resistant to viral evolution and can even provide broad prevention against SARS-CoV and HCoV-NL63. Here, we use prime editor (PE) to precisely edit ACE2 at structurally selected sites. We demonstrated that residue changes at Q24/D30/K31 and/or K353 of ACE2 could completely ablate the binding of tested viruses while maintaining its physiological role in host angiotensin II conversion. PE-mediated ACE2 editing at these sites suppressed the entry of pseudotyped SARS-CoV-2 major variants of concern and even SARS-CoV or HCoV-NL63. Moreover, it significantly inhibited the replication of the Delta variant live virus. Our work investigated the unexplored application potential of prime editing in high-risk infectious disease control and demonstrated that such gene editing-based host factor reshaping strategy can provide broad-spectrum antiviral activity and a high barrier to viral escape or resistance.

Wavelength-Dependent Shaping of Azopolymer Micropillars for Three-Dimensional Structure Control.

Surfaces endowed with three-dimensional (3D) mesostructures, showing features in the nanometer to micrometer range, are critical for applications in several fields of science and technology. Finding a fabrication method that is simultaneously inexpensive, simple, fast, versatile, highly scalable, and capable of producing complex 3D shapes is still a challenge. Herein, we characterize the photoreconfiguration of a micropillar array of an azobenzene-containing polymer at different light wavelengths and demonstrate the tailoring of the surface geometry and its related functionality only using light. By changing the irradiated light wavelength and its polarization, we demonstrate the fabrication of various complex isotropic and anisotropic 3D mesostructures from a single original pristine geometry. Quantitative morphological analyses revealed an interplay between the decay rate of absorbed light intensity, micropillar volume preservation, and the cohesive forces between the azopolymer chains as the origin of distinctive wavelength-dependent 3D structural remorphing. Finally, we show the potentialities of this method in surface engineering by photoreshaping a single original micropillar surface into two sets of different mesostructured surfaces exhibiting tunable hydrophobicity in a wide water contact angle range. Our study opens up a new paradigm for fabricating functional 3D mesostructures in a simple, low-cost, fast, and scalable manner.

Wrisberg variant of the lateral discoid meniscus in children: review of the literature and presentation of case series.

INTRODUCTION: The Wrisberg variant of the discoid lateral meniscus is a very rare disorder and is characterized by the hypermobility and instability of the meniscus caused by the absence of its posterior tibial attachment, with only its meniscofemoral junction (Wrisberg's ligament) maintained, and inserted in the posterior horn of the meniscus. As a result, the posterior horn of the lateral meniscus is mobile; often subluxing into the joint. MATERIALS AND METHODS: A total of eight skeletally immature patients with symptomatic Wrisberg variant of the discoid lateral meniscus were included in this study. Each knee was evaluated with MRI and arthroscopy. We graded unstable discoid menisci according to their discoid morphology (complete vs. incomplete), meniscal intra-substance degeneration, and the presence or absence of meniscal tears. All eight menisci were evaluated as degenerated with no meniscal tears. Five of them were evaluated as complete. Due to the severely degenerated meniscus, we considered it unnecessary to repair the detached posterior tibial ligament, so we performed a reshaping of the discoid meniscus, restoring a C-shape, excising the hypertrophied central part of the meniscus, and creating a posterior horn with a remaining rim of 6-8 mm. For evaluation of the knee function preoperatively and postoperatively we used the online International Knee Documentation Committee (IKDC) system. The purpose of this study is to emphasize the importance of MRI in identifying and revealing the unstable (Wrisberg variant) type of discoid meniscus in children. RESULTS: The mean patient age at the time of surgery was 8.25 ± 2.91 years (range 5-13 years). The average follow-up was 3.75 ± 0.46 years (range 3-4) years. The mean preoperative IKDC score was 22.37 ± 1.50 (range 21-25) points. The mean postoperative IKDC score was 80.50 ± 1.77 (range 79-84) points. CONCLUSIONS: MRI is a valuable tool in the evaluation of the shape, stability, and consistency of symptomatic discoid menisci. It is helpful for the detection of the unstable Wrisberg variant.

rRNA intermediates coordinate the formation of nucleolar vacuoles in C. elegans.

The nucleolus is the most prominent membraneless organelle within the nucleus. How the nucleolar structure is regulated is poorly understood. Here, we identified two types of nucleoli in C. elegans. Type I nucleoli are spherical and do not have visible nucleolar vacuoles (NoVs), and rRNA transcription and processing factors are evenly distributed throughout the nucleolus. Type II nucleoli contain vacuoles, and rRNA transcription and processing factors exclusively accumulate in the periphery rim. The NoV contains nucleoplasmic proteins and is capable of exchanging contents with the nucleoplasm. The high-order structure of the nucleolus is dynamically regulated in C. elegans. Faithful rRNA processing is important to prohibit NoVs. The depletion of 27SA2 rRNA processing factors resulted in NoV formation. The inhibition of RNA polymerase I (RNAPI) transcription and depletion of two conserved nucleolar factors, nucleolin and fibrillarin, prohibits the formation of NoVs. This finding provides a mechanism to coordinate structure maintenance and gene expression.

Transapical ventricular reshaping reduces functional mitral regurgitation and improves ventricular function in a preclinical model of ischemic cardiomyopathy.

OBJECTIVE: A significant proportion of patients with advanced heart failure present with dilated left ventricles and functional mitral regurgitation. These patients currently have limited treatment options. The MitraClip device (Abbott) has benefited only patients with smaller left ventricles (end-diastolic dimension <70 mm), whereas those with larger left ventricles did not benefit. A possible explanation is correcting functional mitral regurgitation alone may not adequately reduce the wall stresses of a dilated left ventricle. We have developed a beating-heart device that not only approximates the papillary muscles to reduce functional mitral regurgitation but also modifies the left ventricle size and shape to reduce wall stress. METHODS: Yorkshire swine (n = 16) had a myocardial infarction induced by permanent occlusion of the left circumflex with intracoronary ethanol. Three months later, the animals developed heart failure and moderate or greater functional mitral regurgitation. Through a transapical approach, the new device was implanted under echocardiography guidance to reshape the left ventricle and correct functional mitral regurgitation. The acute impact of this approach on the mitral valve and left ventricle was assessed with echocardiography and invasive hemodynamics. RESULTS: After reshaping, echocardiography showed a decrease in end-diastolic volume by 36.3 ± 30.5 mL (P < .001), a decrease in sphericity index by 0.143 ± 0.087 (P < .001), and an increase in ejection fraction of 5.90% ± 6.38% (P < .01). Mitral valve tenting area was reduced by 39.29 ± 33.66 mm2 (P < .001), coaptation length was increased by 2.12 ± 1.02 mm (P < .001), and posterior excursion angle was improved by 9.07° ± 9.14° (P < .01), resulting in functional mitral regurgitation reduction. CONCLUSIONS: Correction of functional mitral regurgitation with favorable changes in mitral valve geometry and reduction in left ventricle geometry is possible with the proposed device.

Sequential Ubiquitination and Phosphorylation Epigenetics Reshaping by MG132-Loaded Fe-MOF Disarms Treatment Resistance to Repulse Metastatic Colorectal Cancer.

Abnormal epigenetic regulation is identified to correlate with cancer progression and renders tumor refractory and resistant to reactive oxygen species (ROS)-based anti-tumor actions. To address it, a sequential ubiquitination and phosphorylation epigenetics modulation strategy is developed and exemplified by the well-established Fe-metal-organic framework (Fe-MOF)-based chemodynamic therapy (CDT) nanoplatforms that load the 26S proteasome inhibitor (i.e., MG132). The encapsulated MG132 can blockade 26S proteasome, terminate ubiquitination, and further inhibit transcription factor phosphorylation (e.g., NF-κB p65), which can boost pro-apoptotic or misfolded protein accumulations, disrupt tumor homeostasis, and down-regulate driving genes expression of metastatic colorectal cancer (mCRC). Contributed by them, Fe-MOF-unlocked CDT is magnified to considerably elevate ROS content for repulsing mCRC, especially after combining with macrophage membrane coating-enabled tropism accumulation. Systematic experiments reveal the mechanism and signaling pathway of such a sequential ubiquitination and phosphorylation epigenetics modulation and explain how it could blockade ubiquitination and phosphorylation to liberate the therapy resistance to ROS and activate NF-κB-related acute immune responses. This unprecedented sequential epigenetics modulation lays a solid foundation to magnify oxidative stress and can serve as a general method to enhance other ROS-based anti-tumor methods.