Diagnosing Sarcopenia with AI-Aided Ultrasound (DINOSAUR)-A Pilot Study.

Background: Sarcopenia has been recognized as a determining factor in surgical outcomes and is associated with an increased risk of postoperative complications and readmission. Diagnosis is currently based on clinical guidelines, which includes assessment of skeletal muscle mass but not quality. Ultrasound has been proposed as a useful point-of-care diagnostic tool to assess muscle quality, but no validated cut-offs for sarcopenia have been reported. Using novel automated artificial intelligence (AI) software to interpret ultrasound images may assist in mitigating the operator-dependent nature of the modality. Our study aims to evaluate the fidelity of AI-aided ultrasound as a reliable and reproducible modality to assess muscle quality and diagnose sarcopenia in surgical patients. Methods: Thirty-six adult participants from an outpatient clinic were recruited for this prospective cohort study. Sarcopenia was diagnosed according to Asian Working Group for Sarcopenia (AWGS) 2019 guidelines. Ultrasonography of the rectus femoris muscle was performed, and images were analyzed by an AI software (MuscleSound® (Version 5.69.0)) to derive muscle parameters including intramuscular adipose tissue (IMAT) as a proxy of muscle quality. A receiver operative characteristic (ROC) curve was used to assess the predictive capability of IMAT and its derivatives, with area under the curve (AUC) as a measure of overall diagnostic accuracy. To evaluate consistency between ultrasound users of different experience, intra- and inter-rater reliability of muscle ultrasound parameters was analyzed in a separate cohort using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: The median age was 69.5 years (range: 26-87), and the prevalence of sarcopenia in the cohort was 30.6%. The ROC curve plotted with IMAT index (IMAT% divided by muscle area) yielded an AUC of 0.727 (95% CI: 0.551-0.904). An optimal cut-off point of 4.827%/cm2 for IMAT index was determined with a Youden's Index of 0.498. We also demonstrated that IMAT index has excellent intra-rater reliability (ICC = 0.938, CI: 0.905-0.961) and good inter-rater reliability (ICC = 0.776, CI: 0.627-0.866). In Bland-Altman plots, the limits of agreement were from -1.489 to 1.566 and -2.107 to 4.562, respectively. Discussion: IMAT index obtained via ultrasound has the potential to act as a point-of-care evaluation for sarcopenia screening and diagnosis, with good intra- and inter-rater reliability. The proposed IMAT index cut-off maximizes sensitivity for case finding, supporting its use as an easily implementable point-of-care test in the community for sarcopenia screening. Further research incorporating other ultrasound parameters of muscle quality may provide the basis for a more robust diagnostic tool to help predict surgical risk and outcomes.

Plin4 exacerbates cadmium-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe2⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe2⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Circular RNA IGF1R Promotes Cardiac Repair via Activating ß-Catenin Signaling by Interacting with DDX5 in Mice after Ischemic Insults.

The potential of circular RNAs (circRNAs) as biomarkers and therapeutic targets is becoming increasingly evident, yet their roles in cardiac regeneration and myocardial renewal remain largely unexplored. Here, we investigated the function of circIGF1R and related mechanisms in cardiac regeneration. Through analysis of circRNA sequencing data from neonatal and adult cardiomyocytes, circRNAs associated with regeneration were identified. Our data showed that circIGF1R expression was high in neonatal hearts, decreased with postnatal maturation, and up-regulated after cardiac injury. The elevation was validated in patients diagnosed with acute myocardial infarction (MI) within 1 week. In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and myocardial tissue from mice after apical resection and MI, we observed that circIGF1R overexpression enhanced cardiomyocyte proliferation, reduced apoptosis, and mitigated cardiac dysfunction and fibrosis, while circIGF1R knockdown impeded endogenous cardiac renewal. Mechanistically, we identified circIGF1R binding proteins through circRNA precipitation followed by mass spectrometry. RNA pull-down Western blot and RNA immunoprecipitation demonstrated that circIGF1R directly interacted with DDX5 and augmented its protein level by suppressing ubiquitin-dependent degradation. This subsequently triggered the ß-catenin signaling pathway, leading to the transcriptional activation of cyclin D1 and c-Myc. The roles of circIGF1R and DDX5 in cardiac regeneration were further substantiated through site-directed mutagenesis and rescue experiments. In conclusion, our study highlights the pivotal role of circIGF1R in facilitating heart regeneration and repair after ischemic insults. The circIGF1R/DDX5/ß-catenin axis emerges as a novel therapeutic target for enhancing myocardial repair after MI, offering promising avenues for the development of regenerative therapies.

Approaching crystal's limit of thermoelectrics by nano-sintering-aid at grain boundaries.

Grain boundary plays a vital role in thermoelectric transports, leading to distinct properties between single crystals and polycrystals. Manipulating the grain boundary to realize good thermoelectric properties in polycrystals similar as those of single crystals is a long-standing task, but it is quite challenging. Herein, we develop a liquid-phase sintering strategy to successfully introduce Mg2Cu nano-sintering-aid into the grain boundaries of Mg3(Bi, Sb)2-based materials. The nano-aid helps to enlarge the average grain size to 23.7 µm and effectively scatter phonons, leading to excellent electrical transports similar as those of single crystals and ultralow lattice thermal conductivity as well as exceptional thermoelectric figure of merit (1.5 at 500 K) and conversion efficiency (7.4% under temperature difference of 207 K). This work provides a simple but effective strategy for the fabrication of high-performance polycrystals for large-scale applications.

Novel PATL2 variants cause female infertility with oocyte maturation defect.

PURPOSE: Oocyte maturation defect (OOMD) is a rare cause of in vitro fertilization failure characterized by the production of immature oocytes. Compound heterozygous or homozygous PATL2 mutations have been associated with oocyte arrest at the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as morphological changes. METHODS: In this study, we recruited three OOMD cases and conducted a comprehensive multiplatform laboratory investigation. RESULTS: Whole exome sequence (WES) revealed four diagnostic variants in PATL2, nonsense mutation c.709C > T (p.R237*) and frameshift mutation c.1486_1487delinsT (p.A496Sfs*4) were novel mutations that have not been reported previously. Furthermore, the pathogenicity of these variants was predicted using in silico analysis, which indicated detrimental effects. Molecular dynamic analysis suggested that the A496S variant disrupted the hydrophobic segment, leading to structural changes that affected the overall protein folding and stability. Additionally, biochemical and molecular experiments were conducted on cells transfected with wild-type (WT) or mutant PATL2 (p.R237* and p.A496Sfs*4) plasmid vectors. CONCLUSIONS: The results demonstrated that PATL2A496Sfs*4 and PATL2R237* had impacts on protein size and expression level. Interestingly, expression levels of specific genes involved in oocyte maturation and early embryonic development were found to be simultaneously deregulated. The findings in our study expand the variation spectrum of the PATL2 gene, provide solid evidence for counseling on future pregnancies in affected families, strongly support the application of in the diagnosis of OOMD, and contribute to the understanding of PATL2 function.

Ductile P-Type AgCu(Se,S,Te) Thermoelectric Materials.

Ductile inorganic thermoelectric (TE) materials open a new approach to develop high-performance flexible TE devices. N-type Ag2(S,Se,Te) and p-type AgCu(Se,S,Te) pseudoternary solid solutions are two typical categories of ductile inorganic TE materials reported so far. Comparing with the Ag2(S,Se,Te) pseudoternary solid solutions, the phase composition, crystal structure, and physical properties of AgCu(Se,S,Te) pseudoternary solid solutions are more complex, but their relationships are still ambiguous now. In this work, via systematically investigating the phase composition, crystal structure, mechanical, and TE properties of about 60 AgCu(Se,S,Te) pseudoternary solid solutions, the comprehensive composition-structure-property phase diagrams of the AgCuSe-AgCuS-AgCuTe pseudoternary system is constructed. By mapping the complex phases, the "ductile-brittle" and "n-p" transition boundaries are determined and the composition ranges with high TE performance and inherent ductility are illustrated. On this basis, high performance p-type ductile TE materials are obtained, with a maximum zT of 0.81 at 340 K. Finally, flexible in-plane TE devices are prepared by using the AgCu(Se,S,Te)-based ductile TE materials, showing high output performance that is superior to those of organic and inorganic-organic hybrid flexible devices.

Vancomycin-Loaded Sol-Gel System for In Situ Coating of Artificial Bone to Prevent Surgical Site Infections.

Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), ß-glycerophosphate (ß-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/ß-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/ß-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/ß-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/ß-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.

Scutellarin alleviates renal ischemia-reperfusion injury by inhibiting the MAPK pathway and pro-inflammatory macrophage polarization.

Renal ischemia-reperfusion injury (IRI) is an integral process in renal transplantation, which results in compromised graft survival. Macrophages play an important role in both the early inflammatory period and late fibrotic period in response to IRI. In this study, we investigated whether scutellarin (SCU) could protect against renal IRI by regulating macrophage polarization. Mice were given SCU (5-50 mg/kg) by gavage 1 h earlier, followed by a unilateral renal IRI. Renal function and pathological injury were assessed 24 h after reperfusion. The results showed that administration of 50 mg/kg SCU significantly improved renal function and renal pathology in IRI mice. In addition, SCU alleviated IRI-induced apoptosis. Meanwhile, it reduced macrophage infiltration and inhibited pro-inflammatory macrophage polarization. Moreover, in RAW 264.7 cells and primary bone marrow-derived macrophages (BMDMs) exposed to SCU, we found that 150 µM SCU inhibited these cells to polarize to an inflammatory phenotype induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). However, SCU has no influence on anti-inflammatory macrophage polarization in vivo and in vitro induced by in interleukin-4 (IL-4). Finally, we explored the effect of SCU on the activation of the mitogen-activated protein kinase (MAPK) pathway both in vivo and in vitro. We found that SCU suppressed the activation of the MAPK pathway, including the extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and p38. Our results demonstrated that SCU protects the kidney against IRI by inhibiting macrophage infiltration and polarization toward pro-inflammatory phenotype via the MAPK pathway, suggesting that SCU may be therapeutically important in treatment of IRI.

Uncovering the phonon spectra and lattice dynamics of plastically deformable InSe van der Waals crystals.

Stacking two-dimensional (2D) van der Waals (vdW) materials in a layered bulk structure provides an appealing platform for the emergence of exotic physical properties. As a vdW crystal with exceptional plasticity, InSe offers the opportunity to explore various effects arising from the coupling of its peculiar mechanical behaviors and other physical properties. Here, we employ neutron scattering techniques to investigate the correlations of plastic interlayer slip, lattice anharmonicity, and thermal transport in InSe crystals. Not only are the interlayer slip direction and magnitude well captured by shifts in the Bragg reflections, but we also observe a deviation from the expected Debye behaviour in the heat capacity and lattice thermal conductivity. Combining the experimental data with first-principles calculations, we tentatively attribute the observed evidence of strong phonon-phonon interactions to a combination of a large acoustic-optical frequency resonance and a nesting effect. These findings correlate the macroscopic plastic slip and the microscopic lattice dynamics, providing insights into the mechano-thermo coupling and modulation in 2D vdW materials.

Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit (GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radio-immunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3.

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Adolescent co-exposure to environmental cadmium and high-fat diet induces cognitive decline via Larp7 m6A-mediated SIRT6 inhibition.

The effects and underlying mechanisms of adolescent exposure to combined environmental hazards on cognitive function remain unclear. Here, using a combined exposure model, we found significant cognitive decline, hippocampal neuronal damage, and neuronal senescence in mice exposed to cadmium (Cd) and high-fat diet (HFD) during adolescence. Furthermore, we observed a significant downregulation of Sirtuin 6 (SIRT6) expression in the hippocampi of co-exposed mice. UBCS039, a specific SIRT6 activator, markedly reversed the above adverse effects. Further investigation revealed that co-exposure obviously reduced the levels of La ribonucleoprotein 7 (LARP7), disrupted the interaction between LARP7 and SIRT6, ultimately decreasing SIRT6 expression in mouse hippocampal neuronal cells. Overexpression of Larp7 reversed the combined exposure-induced SIRT6 decrease and senescence in mouse hippocampal neuronal cells. Additionally, the results showed notably elevated levels of Larp7 m6A and YTH domain family protein 2 (YTHDF2) in mouse hippocampal neuronal cells treated with the combined hazards. Ythdf2 short interfering RNA, RNA immunoprecipitation, and RNA stability assays further demonstrated that YTHDF2 mediated the degradation of Larp7 mRNA under combined exposure. Collectively, adolescent co-exposure to Cd and HFD causes hippocampal senescence and cognitive decline in mice by inhibiting LARP7-mediated SIRT6 expression in an m6A-dependent manner.

Exploring drug repositioning possibilities of kinase inhibitors via molecular simulation.

Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC50 values of 3.3, 3.2 and 5.8 µM. Further cell assays showed IC50 values of 0.2, 1.2 and 0.6 µM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible.

Health-related quality of life in pregnant women with type 1 diabetes and associations with maternal and neonatal complications.

PURPOSE: Preexisting type 1 diabetes is a stressful situation for women in pregnancy. We aimed to evaluate health-related quality of life (HRQoL) during pregnancy in women with type 1 diabetes and examine the association between HRQoL and pregnancy outcomes. METHODS: This multicenter prospective cohort study involved 115 pregnant women with type 1 diabetes from 11 participating centers in China. HRQoL was investigated in three trimesters using European Quality-of-life 5-Dimension 5-Level questionnaire (EQ-5D-5 L). Chinese time trade-off value method was used to calculate the EQ-5D-5 L score. Multivariable logistic regression model was used to evaluate the effect of HRQoL on maternal and neonatal outcomes. Receiver operating characteristic curves and distribution-based methods were employed to estimate minimally important differences of clinically important decline in HRQoL. RESULTS: 50.43% of the studied women with type 1 diabetes reported impaired HRQoL in pregnancy. Estimated maternal HRQoL significantly decreased from early to mid-pregnancy (mean EQ-5D-5 L score 0.97 in the first trimester and 0.91 in the second trimester) and improved slightly in late pregnancy (mean EQ-5D-5 L score 0.95). Multivariable regression model showed that women who experienced impaired HRQoL in pregnancy had higher risk of hypertensive disorder, preterm birth, and composite pregnancy outcome. The estimated minimally important difference for composite pregnancy outcome was -0.045 to -0.043. CONCLUSIONS: Experiencing impaired HRQoL during pregnancy was associated with a higher risk of hypertensive disorder and preterm birth in women with type 1 diabetes. The estimated minimally important difference of EQ-5D-5 L might serve as a clinically important tool in prenatal care. TRIAL REGISTRATION: No.ChiCTR1900025955.

Research Progress on Ti3C2Tx-Based Composite Materials in Antibacterial Field.

The integration of two-dimensional Ti3C2Tx nanosheets and other materials offers broader application options in the antibacterial field. Ti3C2Tx-based composites demonstrate synergistic physical, chemical, and photodynamic antibacterial activity. In this review, we aim to explore the potential of Ti3C2Tx-based composites in the fabrication of an antibiotic-free antibacterial agent with a focus on their systematic classification, manufacturing technology, and application potential. We investigate various components of Ti3C2Tx-based composites, such as metals, metal oxides, metal sulfides, organic frameworks, photosensitizers, etc. We also summarize the fabrication techniques used for preparing Ti3C2Tx-based composites, including solution mixing, chemical synthesis, layer-by-layer self-assembly, electrostatic assembly, and three-dimensional (3D) printing. The most recent developments in antibacterial application are also thoroughly discussed, with special attention to the medical, water treatment, food preservation, flexible textile, and industrial sectors. Ultimately, the future directions and opportunities are delineated, underscoring the focus of further research, such as elucidating microscopic mechanisms, achieving a balance between biocompatibility and antibacterial efficiency, and investigating effective, eco-friendly synthesis techniques combined with intelligent technology. A survey of the literature provides a comprehensive overview of the state-of-the-art developments in Ti3C2Tx-based composites and their potential applications in various fields. This comprehensive review covers the variety, preparation methods, and applications of Ti3C2Tx-based composites, drawing upon a total of 171 English-language references. Notably, 155 of these references are from the past five years, indicating significant recent progress and interest in this research area.

Checkpoint Kinase 1 Stimulates Endogenous Cardiomyocyte Renewal and Cardiac Repair by Binding to Pyruvate Kinase Isoform M2 C-Domain and Activating Cardiac Metabolic Reprogramming in a Porcine Model of Myocardial Ischemia/Reperfusion Injury.

BACKGROUND: The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. METHODS AND RESULTS: Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming. CONCLUSIONS: This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.

Disentangling oncogenic amplicons in esophageal adenocarcinoma.

Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids to disentangle complex amplicons and their associated mechanisms. Short-read sequencing identifies ERBB2, MYC, MDM2, and HMGA2 as the most frequent oncogenes amplified in extrachromosomal DNAs. We resolve complex extrachromosomal DNA and breakage-fusion-bridge cycles amplicons by integrating of de-novo assemblies and DNA methylation in nine long-read sequenced cases. Complex amplicons shared between precancerous biopsy and late-stage tumor, an enrichment of putative enhancer elements and mobile element insertions are potential drivers of complex amplicons' origin. We find that patient-derived organoids recapitulate extrachromosomal DNA observed in the primary tumors and single-cell DNA sequencing capture extrachromosomal DNA-driven clonal dynamics across passages. Prospectively, long-read and single-cell DNA sequencing technologies can lead to better prediction of clonal evolution in esophageal adenocarcinoma.

Efficacy of maxillary molar intrusion and quantification of related external apical root resorption - A comparison of two approaches.

OBJECTIVE: This retrospective single-centre study aimed to compare the efficacy of maxillary second molar intrusion with two different approaches, miniscrew-assisted molar intrusion and traditional segmental archwire intrusion, and to compare orthodontically induced external apical root resorption (OIERR) during intrusion between two groups via cone beam computed tomography (CBCT). MATERIALS AND METHODS: A total of 40 adult patients (33.6 ± 10.3 years old) with supraerupted maxillary second molars due to the loss of antagonistic teeth were recruited, with 20 patients in each group. A segmental archwire with adjacent teeth as an anchorage was used in the control group, and 60-100 g of intrusive force was applied by using miniscrews in the experimental group to intrude the overerupted molars. Full-volume CBCT was performed before and after intrusion, and the amount of intrusion and extent of OIERR of the overerupted molars were compared between the two groups. RESULTS: Supraerupted maxillary second molars could be successfully intruded in an average of 5 months. There was more intrusive movement of the buccal and palatal cusps in the mininscrew group than that in the segmental archwire group (P < .05). The intrusive amount of palatal cusp was 3.67 ± 1.13 mm in the miniscrew group and 2.38 ± 0.74 mm in the segmental archwire group. More palatal OIERR was observed in the miniscrew group (30.3 ± 11.6 mm3) than in the segmental archwire group (21.0 ± 8.66 mm3) (P = .0063). There was no significant difference in OIERR between the two groups for mesial and distal buccal roots (P > .05). CONCLUSION: Miniscrews help effectively with supraerupted maxillary second molar intrusion, especially for palatal cusps. There was more OIERR in the palatal root when using miniscrews compared to the segmental archwire approach.

Progress of Mitochondrial Function Regulation in Cardiac Regeneration.

Heart failure and myocardial infarction, global health concerns, stem from limited cardiac regeneration post-injury. Myocardial infarction, typically caused by coronary artery blockage, leads to cardiac muscle cell damage, progressing to heart failure. Addressing the adult heart's minimal self-repair capability is crucial, highlighting cardiac regeneration research's importance. Studies reveal a metabolic shift from anaerobic glycolysis to oxidative phosphorylation in neonates as a key factor in impaired cardiac regeneration, with mitochondria being central. The heart's high energy demands rely on a robust mitochondrial network, essential for cellular energy, cardiac health, and regenerative capacity. Mitochondria's influence extends to redox balance regulation, signaling molecule interactions, and apoptosis. Changes in mitochondrial morphology and quantity also impact cardiac cell regeneration. This article reviews mitochondria's multifaceted role in cardiac regeneration, particularly in myocardial infarction and heart failure models. Understanding mitochondrial function in cardiac regeneration aims to enhance myocardial infarction and heart failure treatment methods and insights.