Essential role for GABARAP autophagy proteins in interferon-inducible GTPase-mediated host defense.

Mammalian autophagy-related 8 (Atg8) homologs consist of LC3 proteins and GABARAPs, all of which are known to be involved in canonical autophagy. In contrast, the roles of Atg8 homologs in noncanonical autophagic processes are not fully understood. Here we show a unique role of GABARAPs, in particular gamma-aminobutyric acid (GABA)-A-receptor-associated protein-like 2 (Gabarapl2; also known as Gate-16), in interferon-γ (IFN-γ)-mediated antimicrobial responses. Cells that lacked GABARAPs but not LC3 proteins and mice that lacked Gate-16 alone were defective in the IFN-γ-induced clearance of vacuolar pathogens such as Toxoplasma. Gate-16 but not LC3b specifically associated with the small GTPase ADP-ribosylation factor 1 (Arf1) to mediate uniform distribution of interferon-inducible GTPases. The lack of GABARAPs reduced Arf1 activation, which led to formation of interferon-inducible GTPase-containing aggregates and hampered recruitment of interferon-inducible GTPases to vacuolar pathogens. Thus, GABARAPs are uniquely required for antimicrobial host defense through cytosolic distribution of interferon-inducible GTPases.

Observation of fractional edge excitations in nanographene spin chains.

Fractionalization is a phenomenon in which strong interactions in a quantum system drive the emergence of excitations with quantum numbers that are absent in the building blocks. Outstanding examples are excitations with charge e/3 in the fractional quantum Hall effect1,2, solitons in one-dimensional conducting polymers3,4 and Majorana states in topological superconductors5. Fractionalization is also predicted to manifest itself in low-dimensional quantum magnets, such as one-dimensional antiferromagnetic S = 1 chains. The fundamental features of this system are gapped excitations in the bulk6 and, remarkably, S = 1/2 edge states at the chain termini7-9, leading to a four-fold degenerate ground state that reflects the underlying symmetry-protected topological order10,11. Here, we use on-surface synthesis12 to fabricate one-dimensional spin chains that contain the S = 1 polycyclic aromatic hydrocarbon triangulene as the building block. Using scanning tunnelling microscopy and spectroscopy at 4.5 K, we probe length-dependent magnetic excitations at the atomic scale in both open-ended and cyclic spin chains, and directly observe gapped spin excitations and fractional edge states therein. Exact diagonalization calculations provide conclusive evidence that the spin chains are described by the S = 1 bilinear-biquadratic Hamiltonian in the Haldane symmetry-protected topological phase. Our results open a bottom-up approach to study strongly correlated phases in purely organic materials, with the potential for the realization of measurement-based quantum computation13.

A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate.

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response1. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.

YF17D-based vaccines - standing on the shoulders of a giant.

Live-attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single-dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS-CoV-2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D-based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D-based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness.

Deficiency of FRMD5 results in neurodevelopmental dysfunction and autistic-like behavior in mice.

The pathophysiology of autism spectrum disorders (ASDs) is causally linked to postsynaptic scaffolding proteins, as evidenced by numerous large-scale genomic studies [1, 2] and in vitro and in vivo neurobiological studies of mutations in animal models [3, 4]. However, due to the distinct phenotypic and genetic heterogeneity observed in ASD patients, individual mutation genes account for only a small proportion (<2%) of cases [1, 5]. Recently, a human genetic study revealed a correlation between de novo variants in FERM domain-containing-5 (FRMD5) and neurodevelopmental abnormalities [6]. In this study, we demonstrate that deficiency of the scaffolding protein FRMD5 leads to neurodevelopmental dysfunction and ASD-like behavior in mice. FRMD5 deficiency results in morphological abnormalities in neurons and synaptic dysfunction in mice. Frmd5-deficient mice display learning and memory dysfunction, impaired social function, and increased repetitive stereotyped behavior. Mechanistically, tandem mass tag (TMT)-labeled quantitative proteomics revealed that FRMD5 deletion affects the distribution of synaptic proteins involved in the pathological process of ASD. Collectively, our findings delineate the critical role of FRMD5 in neurodevelopment and ASD pathophysiology, suggesting potential therapeutic implications for the treatment of ASD.

Programmable Ferroelectricity in Hf0.5Zr0.5O2 Enabled by Oxygen Defect Engineering.

Ferroelectricity, especially the Si-compatible type recently observed in hafnia-based materials, is technologically useful for modern memory and logic applications, but it is challenging to differentiate intrinsic ferroelectric polarization from the polar phase and oxygen vacancy. Here, we report electrically controllable ferroelectricity in a Hf0.5Zr0.5O2-based heterostructure with Sr-doped LaMnO3, a mixed ionic-electronic conductor, as an electrode. Electrically reversible extraction and insertion of an oxygen vacancy into Hf0.5Zr0.5O2 are macroscopically characterized and atomically imaged in situ. Utilizing this reversible process, we achieved multilevel polarization states modulated by the electric field. Our study demonstrates the usefulness of the mixed conductor to repair, create, manipulate, and utilize advanced ferroelectric functionality. Furthermore, the programmed ferroelectric heterostructures with Si-compatible doped hafnia are desirable for the development of future ferroelectric electronics.

Cove-Edged Chiral Graphene Nanoribbons with Chirality-Dependent Bandgap and Carrier Mobility.

Graphene nanoribbons (GNRs) have garnered significant interest due to their highly customizable physicochemical properties and potential utility in nanoelectronics. Besides controlling widths and edge structures, the inclusion of chirality in GNRs brings another dimension for fine-tuning their optoelectronic properties, but related studies remain elusive owing to the absence of feasible synthetic strategies. Here, we demonstrate a novel class of cove-edged chiral GNRs (CcGNRs) with a tunable chiral vector (n,m). Notably, the bandgap and effective mass of (n,2)-CcGNR show a distinct positive correlation with the increasing value of n, as indicated by theory. Within this GNR family, two representative members, namely, (4,2)-CcGNR and (6,2)-CcGNR, are successfully synthesized. Both CcGNRs exhibit prominently curved geometries arising from the incorporated [4]helicene motifs along their peripheries, as also evidenced by the single-crystal structures of the two respective model compounds (1 and 2). The chemical identities and optoelectronic properties of (4,2)- and (6,2)-CcGNRs are comprehensively investigated via a combination of IR, Raman, solid-state NMR, UV-vis, and THz spectroscopies as well as theoretical calculations. In line with theoretical expectation, the obtained (6,2)-CcGNR possesses a low optical bandgap of 1.37 eV along with charge carrier mobility of ∼8 cm2 V-1 s-1, whereas (4,2)-CcGNR exhibits a narrower bandgap of 1.26 eV with increased mobility of ∼14 cm2 V-1 s-1. This work opens up a new avenue to precisely engineer the bandgap and carrier mobility of GNRs by manipulating their chiral vector.

Exceptionally clean single-electron transistors from solutions of molecular graphene nanoribbons.

Only single-electron transistors with a certain level of cleanliness, where all states can be properly accessed, can be used for quantum experiments. To reveal their exceptional properties, carbon nanomaterials need to be stripped down to a single element: graphene has been exfoliated into a single sheet, and carbon nanotubes can reveal their vibrational, spin and quantum coherence properties only after being suspended across trenches1-3. Molecular graphene nanoribbons4-6 now provide carbon nanostructures with single-atom precision but suffer from poor solubility, similar to carbon nanotubes. Here we demonstrate the massive enhancement of the solubility of graphene nanoribbons by edge functionalization, to yield ultra-clean transport devices with sharp single-electron features. Strong electron-vibron coupling leads to a prominent Franck-Condon blockade, and the atomic definition of the edges allows identifying the associated transverse bending mode. These results demonstrate how molecular graphene can yield exceptionally clean electronic devices directly from solution. The sharpness of the electronic features opens a path to the exploitation of spin and vibrational properties in atomically precise graphene nanostructures.

Exceptionally high charge mobility in phthalocyanine-based poly(benzimidazobenzophenanthroline)-ladder-type two-dimensional conjugated polymers.

Two-dimensional conjugated polymers (2DCPs), composed of multiple strands of linear conjugated polymers with extended in-plane π-conjugation, are emerging crystalline semiconducting polymers for organic (opto)electronics. They are represented by two-dimensional π-conjugated covalent organic frameworks, which typically suffer from poor π-conjugation and thus low charge carrier mobilities. Here we overcome this limitation by demonstrating two semiconducting phthalocyanine-based poly(benzimidazobenzophenanthroline)-ladder-type 2DCPs (2DCP-MPc, with M = Cu or Ni), which are constructed from octaaminophthalocyaninato metal(II) and naphthalenetetracarboxylic dianhydride by polycondensation under solvothermal conditions. The 2DCP-MPcs exhibit optical bandgaps of ~1.3 eV with highly delocalized π-electrons. Density functional theory calculations unveil strongly dispersive energy bands with small electron-hole reduced effective masses of ~0.15m0 for the layer-stacked 2DCP-MPcs. Terahertz spectroscopy reveals the band transport of Drude-type free carriers in 2DCP-MPcs with exceptionally high sum mobility of electrons and holes of ~970 cm2 V-1 s-1 at room temperature, surpassing that of the reported linear conjugated polymers and 2DCPs. This work highlights the critical role of effective conjugation in enhancing the charge transport properties of 2DCPs and the great potential of high-mobility 2DCPs for future (opto)electronics.

High-throughput sequencing reveals differences in microbial community structure and diversity in the conjunctival tissue of healthy and type 2 diabetic mice.

BACKGROUND: To investigate the differences in bacterial and fungal community structure and diversity in conjunctival tissue of healthy and diabetic mice. METHODS: RNA-seq assays and high-throughput sequencing of bacterial 16 S rDNA and fungal internal transcribed spacer (ITS) gene sequences were used to identify differentially expressed host genes and fungal composition profiles in conjunctival tissues of diabetic BKS-db/db mice and BKS (control) mice. Functional enrichment analysis of differentially expressed genes and the correlation between the relative abundance of bacterial and fungal taxa in the intestinal mucosa were also performed. RESULTS: Totally, 449 differential up-regulated genes and 1,006 down-regulated genes were identified in the conjunctival tissues of diabetic mice. The differentially expressed genes were mainly enriched in metabolism-related functions and pathways. A decrease in conjunctival bacterial species diversity and abundance in diabetic mice compared to control mice. In contrast, fungal species richness and diversity were not affected by diabetes. The microbial colonies were mainly associated with cellular process pathways regulating carbohydrate and lipid metabolism, as well as cell growth and death. Additionally, some interactions between bacteria and fungi at different taxonomic levels were also observed. CONCLUSION: The present study revealed significant differences in the abundance and composition of bacterial and fungal communities in the conjunctival tissue of diabetic mice compared to control mice. The study also highlighted interactions between bacteria and fungi at different taxonomic levels. These findings may have implications for the diagnosis and treatment of diabetes.

Tailoring Magnetism of Graphene Nanoflakes via Tip-Controlled Dehydrogenation.

Atomically precise graphene nanoflakes called nanographenes have emerged as a promising platform to realize carbon magnetism. Their ground state spin configuration can be anticipated by Ovchinnikov-Lieb rules based on the mismatch of π electrons from two sublattices. While rational geometrical design achieves specific spin configurations, further direct control over the π electrons offers a desirable extension for efficient spin manipulations and potential quantum device operations. To this end, we apply a site-specific dehydrogenation using a scanning tunneling microscope tip to nanographenes deposited on a Au(111) substrate, which shows the capability of precisely tailoring the underlying π-electron system and therefore efficiently manipulating their magnetism. Through first-principles calculations and tight-binding mean-field-Hubbard modeling, we demonstrate that the dehydrogenation-induced Au-C bond formation along with the resulting hybridization between frontier π orbitals and Au substrate states effectively eliminate the unpaired π electron. Our results establish an efficient technique for controlling the magnetism of nanographenes.

DFT Study on the Mechanisms and Selectivities in Rh (III)-Catalyzed [5 + 1] Annulation of 2-Alkenylanilides and 2-Alkylphenols with Allenyl Acetates.

The mechanisms and regio-, chemo-, and stereoselectivity were theoretically investigated in the Rh(III)-catalyzed [5 + 1] annulation of 2-alkenylanilides and 2-alkylphenols with allenyl acetates. Two different reactants, 2-alkenylanilides and 2-alkylphenols, were selected as model systems in the density functional theory calculations. The obtained theoretical results show that both these reactants exhibit similar steps, namely, (1) N-H/O-H deprotonation and C-H activation, (2) allenyl acetate migratory insertion, (3) ß-oxygen elimination, (4) intramolecular nucleophilic addition of the nitrogen/oxygen-rhodium bond resulting in [5 + 1]-annulation, and (5) protonation with the formation of the desired product and regeneration of the Rh(III) catalyst. The theoretical evidence suggests that the selectivity is determined at the step of allenyl acetate's migratory insertion. Moreover, the regioselectivity is driven by electronic effects, while the interaction energies (C-H···π and C-H···O interactions) play a more imperative role in controlling the stereoselectivity. The obtained theoretical results not only well rationalize the experimental observations but also provide important mechanistic insights for related types of [5 + 1]-annulation reactions.

Photoredox-Catalyzed Tandem Cyclization of Enaminones with N-Sulfonylaminopyridinium Salts toward the Synthesis of 3-Sulfonaminated Chromones.

A photoredox-catalyzed intermolecular tandem sulfonamination/cyclization of enaminones was realized by using N-aminopyridinium salts as the sulfonaminated reagents without transition-metal catalysts or bases. The reaction exhibits a broad scope and good functional group tolerance, good yields, and regioselectivity. Preliminary mechanistic studies support the radical property of the reaction and the involvement of N-centered radical intermediates.

Association of elevated circulating monocyte-platelet aggregates with hypercoagulability in patients with nephrotic syndrome.

BACKGROUND: Hypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome. METHODS: Thirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry. RESULTS: Patients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p < 0.001). The percentages of MPAs with CM, IM, and NCM were higher than those of healthy controls (p = 0.012, p < 0.001 and p < 0.001, respectively). Circulating MPAs showed correlations with hypoalbuminemia (r=-0.85; p < 0.001), hypercholesterolemia (r = 0.54; p < 0.001), fibrinogen (r = 0.70; p < 0.001) and D-dimer (r = 0.37; p = 0.003), but not with hypertriglyceridemia in nephrotic syndrome. The AUC for the prediction of hypercoagulability in nephrotic syndrome using MPAs was 0.79 (95% CI 0.68-0.90, p < 0.001). The sensitivity of MPAs in predicting hypercoagulability was 0.71, and the specificity was 0.78. CONCLUSION: Increased MPAs were correlated with hypercoagulability in nephrotic syndrome. MPAs may serve as a potential biomarker for thrombophilic or hypercoagulable state and provide novel insight into the mechanisms of anticoagulation in nephrotic syndrome.

Correlation between PD-1 and sPD-L1 expression levels in peripheral blood of DLBCL patients and their clinicopathological characteristics.

Molecular pathology and clinical characteristics play a crucial role in guiding treatment selection and predicting the prognosis of diffuse large B-cell lymphoma (DLBCL). The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), have emerged as pivotal regulators of immune checkpoints in cancer. The objectives of this study are to investigate the correlation between the expression levels of PD-1 and soluble PD-L1 (sPD-L1) in the peripheral blood of DLBCL patients, analyze their clinicopathological characteristics, and identify the optimal beneficiary group for PD-1/PD-L1 blockade. Peripheral blood samples were collected from 36 DLBCL patients before their initial treatment at Shandong Cancer Hospital between December 2018 and July 2019. The expression levels of PD-1 and sPD-L1 were measured using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The clinicopathological characteristics, including age, sex, Ann Arbor stage, International Prognostic Index (IPI) score, response to treatment, etc., were recorded for each patient. The surface expression of PD-1 on peripheral blood T cells was significantly higher in DLBCL patients compared to healthy controls. There was a significant association between elevated PD-1 expression levels and the advanced Ann Arbor stage (P=0.0153) as well as the B group (P=0.0184). Higher sPD-L1 levels were associated with the GCB subtype according to Hans's classification (P=0.0435). The expression levels of PD-1 and sPD-L1 in the peripheral blood of DLBCL patients are significantly correlated with advanced disease stage, B group, and GCB subtype according to Hans's classification. This suggests that the PD-1/PD-L1 axis play a critical role in specific subgroups of DLBCL. Targeting this axis could serve as a potential therapeutic strategy to enhance the clinical outcomes of DLBCL patients. Further studies are necessary to explore the prognostic implications of PD-1 and sPD-L1 expression levels in DLBCL patients.

Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19.

BACKGROUND: Development of safe and effective SARS-CoV-2 therapeutics is a high priority. Amubarvimab and romlusevimab are noncompeting anti-SARS-CoV-2 monoclonal antibodies with an extended half-life. OBJECTIVE: To assess the safety and efficacy of amubarvimab plus romlusevimab. DESIGN: Randomized, placebo-controlled, phase 2 and 3 platform trial. (ClinicalTrials.gov: NCT04518410). SETTING: Nonhospitalized patients with COVID-19 in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines. PATIENTS: Adults within 10 days onset of symptomatic SARS-CoV-2 infection who are at high risk for clinical progression. INTERVENTION: Combination of monoclonal antibodies amubarvimab plus romlusevimab or placebo. MEASUREMENTS: Nasopharyngeal and anterior nasal swabs for SARS-CoV-2, COVID-19 symptoms, safety, and progression to hospitalization or death. RESULTS: Eight-hundred and seven participants who initiated the study intervention were included in the phase 3 analysis. Median age was 49 years (quartiles, 39 to 58); 51% were female, 18% were Black, and 50% were Hispanic or Latino. Median time from symptom onset at study entry was 6 days (quartiles, 4 to 7). Hospitalizations and/or death occurred in 9 (2.3%) participants in the amubarvimab plus romlusevimab group compared with 44 (10.7%) in the placebo group, with an estimated 79% reduction in events (P < 0.001). This reduction was similar between participants with 5 or less and more than 5 days of symptoms at study entry. Grade 3 or higher treatment-emergent adverse events through day 28 were seen less frequently among participants randomly assigned to amubarvimab plus romlusevimab (7.3%) than placebo (16.1%) (P < 0.001), with no severe infusion reactions or drug-related serious adverse events. LIMITATION: The study population was mostly unvaccinated against COVID-19 and enrolled before the spread of Omicron variants and subvariants. CONCLUSION: Amubarvimab plus romlusevimab was safe and significantly reduced the risk for hospitalization and/or death among nonhospitalized adults with mild to moderate SARS-CoV-2 infection at high risk for progression to severe disease. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Diagnostic and prognostic nomograms for laryngeal carcinoma patients with lung metastasis: a SEER-based study.

PURPOSE: To establish two nomograms to quantify the risk of lung metastasis (LM) in laryngeal carcinoma (LC) and predict the overall survival of LC patients with LM. METHODS: Totally 9515 LC patients diagnosed histologically from 2000 to 2019 were collected from the Surveillance, Epidemiology, and End Results database. The independent diagnostic factors for LM in LC patients and prognostic factors for LC patients with LM were identified by logistic and Cox regression analysis, respectively. Nomograms were established based on regression coefficients and evaluated by receiver operating characteristic curve, calibration curves, and decision curve analysis. RESULTS: Patients with supraglottis, higher pathological grade, higher N stage, and distant metastasis (bone, brain, or liver) were more likely to have LM (P < 0.05). Chemotherapy, surgery and radiotherapy were independent factors of the overall survival of LC patients with LM (P < 0.05). The area under curve of diagnostic nomogram were 0.834 and 0.816 in the training and validation cohort respectively. For the prognostic nomogram, the area under curves of 1-, 2-, and 3-years were 0.735, 0.734, and 0.709 in the training cohort and 0.705, 0.803, and 0.809 in the validation cohort. The calibration curves and decision curve analysis indicated good performance of the nomograms. CONCLUSION: Distant metastasis (bone, brain, or liver) and N stage should be considered for prediction of LM in LC patients. Chemotherapy is the most significant influencing prognostic factor improving the survival of LC patients with LM. Two nomograms may benefit for providing better precautionary measures and treatment decision.

Using unsupervised learning to classify inlet water for more stable design of water reuse in industrial parks.

The water reuse facilities of industrial parks face the challenge of managing a growing variety of wastewater sources as their inlet water. Typically, this clustering outcome is designed by engineers with extensive expertise. This paper presents an innovative application of unsupervised learning methods to classify inlet water in Chinese water reuse stations, aiming to reduce reliance on engineer experience. The concept of 'water quality distance' was incorporated into three unsupervised learning clustering algorithms (K-means, DBSCAN, and AGNES), which were validated through six case studies. Of the six cases, three were employed to illustrate the feasibility of the unsupervised learning clustering algorithm. The results indicated that the clustering algorithm exhibited greater stability and excellence compared to both artificial clustering and ChatGPT-based clustering. The remaining three cases were utilized to showcase the reliability of the three clustering algorithms. The findings revealed that the AGNES algorithm demonstrated superior potential application ability. The average purity in six cases of K-means, DBSCAN, and AGNES were 0.947, 0.852, and 0.955, respectively.

Adults Ischium Age Estimation Based on Deep Learning and 3D CT Reconstruction.

OBJECTIVES: To develop a deep learning model for automated age estimation based on 3D CT reconstructed images of Han population in western China, and evaluate its feasibility and reliability. METHODS: The retrospective pelvic CT imaging data of 1 200 samples (600 males and 600 females) aged 20.0 to 80.0 years in western China were collected and reconstructed into 3D virtual bone models. The images of the ischial tuberosity feature region were extracted to create sex-specific and left/right site-specific sample libraries. Using the ResNet34 model, 500 samples of different sexes were randomly selected as training and verification set, the remaining samples were used as testing set. Initialization and transfer learning were used to train images that distinguish sex and left/right site. Mean absolute error (MAE) and root mean square error (RMSE) were used as primary indicators to evaluate the model. RESULTS: Prediction results varied between sexes, with bilateral models outperformed left/right unilateral ones, and transfer learning models showed superior performance over initial models. In the prediction results of bilateral transfer learning models, the male MAE was 7.74 years and RMSE was 9.73 years, the female MAE was 6.27 years and RMSE was 7.82 years, and the mixed sexes MAE was 6.64 years and RMSE was 8.43 years. CONCLUSIONS: The skeletal age estimation model, utilizing ischial tuberosity images of Han population in western China and employing the ResNet34 combined with transfer learning, can effectively estimate adult ischium age.

Proximity-Enhanced Functional Imaging Analysis of Engineered Tumors.

Functional imaging (FI) techniques have revolutionized tumor imaging by providing information on specific tumor functions, such as glycometabolism. However, tumor cells lack unique molecular characteristics at the molecular level and metabolic pathways, resulting in limited metabolic differences compared to normal cells and increased background signals from FI. To address this limitation, we developed a novel imaging technique termed proximity-enhanced functional imaging (PEFI) for accurate visualization of tumors. By using "two adjacent chemically labeled glycoproteins" as output signals, we significantly enhance the metabolic differences between tumor and normal cells by PEFI, thereby reducing the background signals for analysis and improving the accuracy of tumor functional imaging. Our results demonstrate that PEFI can accurately identify tumors at the cellular, tissue, and animal level, and has potential value in clinical identification and analysis of tumor cells and tissues, as well as in the guidance of clinical tumor resection surgery.