CD201+ fascia progenitors choreograph injury repair.

Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation1. Here we identify a multipotent fibroblast progenitor marked by CD201 expression in the fascia, the deepest connective tissue layer of the skin. Using skin injury models in mice, single-cell transcriptomics and genetic lineage tracing, ablation and gene deletion models, we demonstrate that CD201+ progenitors control the pace of wound healing by generating multiple specialized cell types, from proinflammatory fibroblasts to myofibroblasts, in a spatiotemporally tuned sequence. We identified retinoic acid and hypoxia signalling as the entry checkpoints into proinflammatory and myofibroblast states. Modulating CD201+ progenitor differentiation impaired the spatiotemporal appearances of fibroblasts and chronically delayed wound healing. The discovery of proinflammatory and myofibroblast progenitors and their differentiation pathways provide a new roadmap to understand and clinically treat impaired wound healing.

Precise arrangement of metal atoms at the interface by a thermal printing strategy.

The kinetics and pathway of most catalyzed reactions depend on the existence of interface, which makes the precise construction of highly active single-atom sites at the reaction interface a desirable goal. Herein, we propose a thermal printing strategy that not only arranges metal atoms at the silica and carbon layer interface but also stabilizes them by strong coordination. Just like the typesetting of Chinese characters on paper, this method relies on the controlled migration of movable nanoparticles between two contact substrates and the simultaneous emission of atoms from the nanoparticle surface at high temperatures. Observed by in situ transmission electron microscopy, a single Fe3O4 nanoparticle migrates from the core of a SiO2 sphere to the surface like a droplet at high temperatures, moves along the interface of SiO2 and the coated carbon layer, and releases metal atoms until it disappears completely. These detached atoms are then in situ trapped by nitrogen and sulfur defects in the carbon layer to generate Fe single-atom sites, exhibiting excellent activity for oxygen reduction reaction. Also, sites' densities can be regulated by controlling the size of Fe3O4 nanoparticle between the two surfaces. More importantly, this strategy is applicable to synthesize Mn, Co, Pt, Pd, Au single-atom sites, which provide a general route to arrange single-atom sites at the interface of different supports for various applications.

Hedgehog signaling is required for larval muscle development and larval metamorphosis of the mussel Mytilus coruscus.

Understanding the developmental processes and signaling pathways involved in larval myogenesis and metamorphosis is crucial for comprehending the life history and adaptive strategies of marine organisms. In this study, we investigated the temporal and spatial patterns of myogenesis in the mussel Mytilus coruscus (Mc), focusing on the emergence and transformation of major muscle groups during different larval stages. We also explored the role of the Hedgehog (Hh) signaling pathway in regulating myogenesis and larval metamorphosis. The results revealed distinct developmental stages characterized by the emergence of specific muscular components, such as velum retractor muscles and anterior adductor muscles, in D-veliger and umbo larvae, which are responsible for the planktonic stage. In the pediveliger stage, posterior ventral, posterior adductor, and foot muscles appeared. After larval metamorphosis, the velum structure and its corresponding retractor muscles degenerate, indicating the transition from planktonic to benthic life. We observed a conserved pattern of larval musculature development and revealed a high degree of conservation across bivalve species, with comparable emergence times during myogenesis. Furthermore, exposure to the Hh signaling inhibitor cyclopamine impaired larval muscle development, reduced larval swimming activity, and inhibited larval metamorphosis in M. coruscus. Cyclopamine-mediated inhibition of Hh signaling led to reduced expression of four key genes within the Hh signaling pathway (McHh, McPtc, McSmo, and McGli) and the striated myosin heavy chain gene (McMHC). It is hypothesised that the abnormal larval muscle development in cyclopamine-treated groups may be an indirect effect due to disrupted McMHC expression. We provide evidence for the first time that cyclopamine treatment inhibited larval metamorphosis in bivalves, highlighting the potential involvement of Hh signaling in mediating larval muscle development and metamorphosis in M. coruscus. The present study provides insights into the dynamic nature of myogenesis and the regulatory role of the Hh signaling pathway during larval development and metamorphosis in M. coruscus. The results obtained in this study contribute to a better understanding of the evolutionary significance of Hh signaling in bivalves and shed light on the mechanisms underlying larval muscle development and metamorphosis in marine invertebrates.

Atomically dispersed iron hydroxide anchored on Pt for preferential oxidation of CO in H2.

Proton-exchange-membrane fuel cells (PEMFCs) are attractive next-generation power sources for use in vehicles and other applications1, with development efforts focusing on improving the catalyst system of the fuel cell. One problem is catalyst poisoning by impurity gases such as carbon monoxide (CO), which typically comprises about one per cent of hydrogen fuel2-4. A possible solution is on-board hydrogen purification, which involves preferential oxidation of CO in hydrogen (PROX)3-7. However, this approach is challenging8-15 because the catalyst needs to be active and selective towards CO oxidation over a broad range of low temperatures so that CO is efficiently removed (to below 50 parts per million) during continuous PEMFC operation (at about 353 kelvin) and, in the case of automotive fuel cells, during frequent cold-start periods. Here we show that atomically dispersed iron hydroxide, selectively deposited on silica-supported platinum (Pt) nanoparticles, enables complete and 100 per cent selective CO removal through the PROX reaction over the broad temperature range of 198 to 380 kelvin. We find that the mass-specific activity of this system is about 30 times higher than that of more conventional catalysts consisting of Pt on iron oxide supports. In situ X-ray absorption fine-structure measurements reveal that most of the iron hydroxide exists as Fe1(OH)x clusters anchored on the Pt nanoparticles, with density functional theory calculations indicating that Fe1(OH)x-Pt single interfacial sites can readily react with CO and facilitate oxygen activation. These findings suggest that in addition to strategies that target oxide-supported precious-metal nanoparticles or isolated metal atoms, the deposition of isolated transition-metal complexes offers new ways of designing highly active metal catalysts.

Dual-Ligand Red Perovskite Ink for Electrohydrodynamic Printing Color Conversion Arrays over 2540 dpi in Near-Eye Micro-LED Display.

The lack of stability of red perovskite nanocrystals (PeNCs) remains the main problem that restricts their patterning application. In this work, the dual-ligand passivation strategy was introduced to stabilize PeNCs and inhibit their halogen ion migration during high-voltage electrohydrodynamic (EHD) inkjet printing. The as-printed red arrays exhibit the highest emisson intensity and least blue shift compared with samples with other passivation strategies under a high electric field during EHD inkjet printing. Combining with blue and green PeNC inks, single-color and tricolor color conversion layer arrays were successfully printed, with minimum pixel size of 5 µm and the highest spatial resolution of 2540 dpi. The color coordinate of CsPbBrI2 NCs arrays are located close to the red point, with a color gumat of 97.28% of Rec. 2020 standard. All of these show great potential in the application of color conversion layers in a near-eye micro-LED display.

Mini-review: Organ Dependency on Fascia connective tissue.

Fascia is a specialized connective tissue system that permiate, encapsulate, and interconnect between tissues and organs throughout the body. The fascia system regulates pain sensation, organ inflammation, trauma, and a fibrotic diseases. This mini-review summarizes recent findings from animal models, which reveal the inter-dependency between tissues/organs and the fascia system. special mechanisms of fascia response to skin inflammatory and fibrotic microenvironment via the dynamics within the fascia in trauma models, the functional heterogeneity of its fascia-born fibroblasts, and cellular communication, to highlight the significance of their stage-specific differentiation to disease progression. Understanding the molecular mechanisms and cellular processes within the fascia microenvironment, may serve as basis for future clinical translation.

Highly Crystalline Iridium-Nickel Nanocages with Subnanopores for Acidic Bifunctional Water Splitting Electrolysis.

Developing efficient bifunctional materials is highly desirable for overall proton membrane water splitting. However, the design of iridium materials with high overall acidic water splitting activity and durability, as well as an in-depth understanding of the catalytic mechanism, is challenging. Herein, we successfully developed subnanoporous Ir3Ni ultrathin nanocages with high crystallinity as bifunctional materials for acidic water splitting. The subnanoporous shell enables Ir3Ni NCs optimized exposure of active sites. Importantly, the nickel incorporation contributes to the favorable thermodynamics of the electrocatalysis of the OER after surface reconstruction and optimized hydrogen adsorption free energy in HER electrocatalysis, which induce enhanced intrinsic activity of the acidic oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Together, the Ir3Ni nanocages achieve 3.72 A/mgIr(η=350 mV) and 4.47 A/mgIr(η=40 mV) OER and HER mass activity, which are 18.8 times and 3.3 times higher than that of commercial IrO2 and Pt, respectively. In addition, their highly crystalline identity ensures a robust nanostructure, enabling good catalytic durability during the oxygen evolution reaction after surface oxidation. This work provides a new revenue toward the structural design and insightful understanding of metal alloy catalytic mechanisms for the bifunctional acidic water splitting electrocatalysis.

Breaking Low-Strain and Deep-Potassiation Trade-Off in Alloy Anodes via Bonding Modulation for High-Performance K-Ion Batteries.

Alloy anode materials have garnered unprecedented attention for potassium storage due to their high theoretical capacity. However, the substantial structural strain associated with deep potassiation results in serious electrode fragmentation and inadequate K-alloying reactions. Effectively reconciling the trade-off between low-strain and deep-potassiation in alloy anodes poses a considerable challenge due to the larger size of K-ions compared to Li/Na-ions. In this study, we propose a chemical bonding modulation strategy through single-atom modification to address the volume expansion of alloy anodes during potassiation. Using black phosphorus (BP) as a representative and generalizing to other alloy anodes, we established a robust P-S covalent bonding network via sulfur doping. This network exhibits sustained stability across discharge-charge cycles, elevating the modulus of K-P compounds by 74%, effectively withstanding the high strain induced by the potassiation process. Additionally, the bonding modulation reduces the formation energies of potassium phosphides, facilitating a deeper potassiation of the BP anode. As a result, the modified BP anode exhibits a high reversible capacity and extended operational lifespan, coupled with a high areal capacity. This work introduces a new perspective on overcoming the trade-off between low-strain and deep-potassiation in alloy anodes for the development of high-energy and stable potassium-ion batteries.

Charge Density-Regulated Microchannel-Based Electrochemiluminescence Sensor for Hydrogen Sulfide Detection with a Highly Efficient Accumulation Strategy.

The electrochemiluminescence (ECL) intensity can be regulated by ionic current passing through the microchannel, which broadened the regulation of the ECL sensors. But in the early reported sensors, the electrostatic repulsion and steric hindrance caused few targets to approach the interface of the microchannel driven by concentration difference, which reduced the detection efficiency and prolonged the detection period. In this study, different accumulation strategies, such as a positive electric field and different polarity electric fields, were designed to accumulate targets in the microchannel. The interaction of azide groups and hydrogen sulfide served as a research model. Hydrogen sulfide can react with the negatively charged azide groups in the microchannel surface to produce positively charged amino groups, decreasing the negative charge density of the microchannel and thus altering the ionic current and ECL intensity. The accumulation of hydrogen sulfide at the microchannel tip can increase the collision probability with azide groups to improve the detection efficiency, and the integration of accumulation and reaction can shorten the detection period to 28 min. The hydrogen sulfide concentration on the microchannel tip accumulated by applying different polarity electric fields was 22.3-fold higher than that accumulated by applying a positive electric field. The selected research model broadened the application range of a microchannel-based ECL sensor and confirmed the universality of the microchannel-based ECL sensor.

Photoelectrochemical Sensor for H2S Based on a Lead-Free Perovskite/Metal-Organic Framework Composite.

Halide perovskites have emerged as a highly promising class of photoelectric materials. However, the application of lead-based perovskites has been hindered by their toxicity and relatively weak stability. In this work, a composite material comprising a lead-free perovskite cesium copper iodide (CsCu2I3) nanocrystal and a metal-organic framework (MOF-801) has been synthesized through an in situ growth approach. The resulting composite material, denoted as CsCu2I3/MOF-801, demonstrates outstanding stability and exceptional optoelectronic characteristics. MOF-801 may serve a dual role by acting as a protective barrier between CsCu2I3 nanocrystals and the external environment, as well as promoting the efficient transfer of photogenerated charge carriers, thereby mitigating their recombination. Consequently, CsCu2I3/MOF-801 demonstrates its utility by providing both stability and a notably high initial photocurrent. Leveraging the inherent reactivity between H2S and the composite material, which results in the formation of Cu2S and structural alteration, an exceptionally sensitive photoelectrochemical sensor for H2S detection has been designed. This sensor exhibits a linear detection range spanning from 0.005 to 100 µM with a remarkable detection limit of 1.67 nM, rendering it highly suitable for precise quantification of H2S in rat brains. This eco-friendly sensor significantly broadens the application horizon of perovskite materials and lays a robust foundation for their future commercialization.

Evaluation of a Cascaded Deep Learning-based Algorithm for Prostate Lesion Detection at Biparametric MRI.

Background Multiparametric MRI (mpMRI) improves prostate cancer (PCa) detection compared with systematic biopsy, but its interpretation is prone to interreader variation, which results in performance inconsistency. Artificial intelligence (AI) models can assist in mpMRI interpretation, but large training data sets and extensive model testing are required. Purpose To evaluate a biparametric MRI AI algorithm for intraprostatic lesion detection and segmentation and to compare its performance with radiologist readings and biopsy results. Materials and Methods This secondary analysis of a prospective registry included consecutive patients with suspected or known PCa who underwent mpMRI, US-guided systematic biopsy, or combined systematic and MRI/US fusion-guided biopsy between April 2019 and September 2022. All lesions were prospectively evaluated using Prostate Imaging Reporting and Data System version 2.1. The lesion- and participant-level performance of a previously developed cascaded deep learning algorithm was compared with histopathologic outcomes and radiologist readings using sensitivity, positive predictive value (PPV), and Dice similarity coefficient (DSC). Results A total of 658 male participants (median age, 67 years [IQR, 61-71 years]) with 1029 MRI-visible lesions were included. At histopathologic analysis, 45% (294 of 658) of participants had lesions of International Society of Urological Pathology (ISUP) grade group (GG) 2 or higher. The algorithm identified 96% (282 of 294; 95% CI: 94%, 98%) of all participants with clinically significant PCa, whereas the radiologist identified 98% (287 of 294; 95% CI: 96%, 99%; P = .23). The algorithm identified 84% (103 of 122), 96% (152 of 159), 96% (47 of 49), 95% (38 of 40), and 98% (45 of 46) of participants with ISUP GG 1, 2, 3, 4, and 5 lesions, respectively. In the lesion-level analysis using radiologist ground truth, the detection sensitivity was 55% (569 of 1029; 95% CI: 52%, 58%), and the PPV was 57% (535 of 934; 95% CI: 54%, 61%). The mean number of false-positive lesions per participant was 0.61 (range, 0-3). The lesion segmentation DSC was 0.29. Conclusion The AI algorithm detected cancer-suspicious lesions on biparametric MRI scans with a performance comparable to that of an experienced radiologist. Moreover, the algorithm reliably predicted clinically significant lesions at histopathologic examination. ClinicalTrials.gov Identifier: NCT03354416 © RSNA, 2024 Supplemental material is available for this article.

Self-Assembly of Super-Uniform Covalent Organic Framework Colloidal Particles into Multi-Dimensional Ordered Superstructures.

Precise self-assembly of colloidal particles is crucial for understanding their aggregation properties and preparing macroscopic functional devices. It is currently very challenging to synthesize and self-assemble super-uniform covalent organic framework (COF) colloidal particles into well-organized multidimensional superstructures. Here, simple and versatile strategies are proposed for synthesis of super-uniform COF colloidal particles and self-assembly of them into 1D supraparticles, 2D ordered mono/multilayers, and 3D COF films. For this purpose, several self-assembly techniques are developed, including emulsion solvent evaporation, air-liquid interfacial self-assembly, and drop-casting. These strategies enable the superstructural self-assembly of particles of varying sizes and species without any additional surfactants or chemical modifications. The assembled superstructures maintain the porosity and high specific surface area of their building blocks. The feasibility of the strategies is examined with different types of COFs. This research provides a new approach for the controllable synthesis of super-uniform COF colloidal particles capable of self-assembling into multidimensional superstructures with long-range order. These discoveries hold great promise for the design of emerging multifunctional COF superstructures.

Amorphous Ni-Fe-Mo Oxides Coupled with Crystalline Metallic Domains for Enhanced Electrocatalytic Oxygen Evolution by Promoted Lattice-Oxygen Participation.

The crystalline/amorphous heterophase nanostructures are promising functional materials for biomedicals, catalysis, energy conversion, and storage. Despite great progress is achieved, facile synthesis of crystalline metal/amorphous multinary metal oxides nanohybrids remains challenging, and their electrocatalytic oxygen evolution reaction (OER) performance along with the catalytic mechanism are not systematically investigated. Herein, two kinds of ultrafine crystalline metal domains coupled with amorphous Ni-Fe-Mo oxides heterophase nanohybrids, including Ni/Ni0.5-a Fe0.5 Mo1.5 Ox and Ni-FeNi3 /Ni0.5-b Fe0.5-y Mo1.5 Ox , are fabricated through controllable reduction of amorphous Ni0.5 Fe0.5 Mo1.5 Ox precursors by simply tuning the amount of used reductant. Due to the suited component in metal domains, the special structure with dense crystalline/amorphous interfaces, and strong electronic coupling of their components, the resultant Ni-FeNi3 /Ni0.5-b Fe0.5-y Mo1.5 Ox nanohybrids show greatly enhanced OER activity with a low overpotential (278 mV) to reach 10 mA cm-2 current density and ultrahigh turnover frequency (38160 h-1 ), outperforming Ni/Ni0.5-a Fe0.5 Mo1.5 Ox , Ni0.5 Fe0.5 Mo1.5 Ox precursors, commercial IrO2 , and most of recently reported OER catalysts. Also, such Ni-FeNi3 /Ni0.5-b Fe0.5-y Mo1.5 Ox nanohybrids manifest good catalytic stability. As revealed by a series of spectroscopy and electrochemical analyses, their OER mechanism follows the lattice-oxygen-mediated (LOM) pathway. This work may shed light on the design of advanced heterophase nanohybrids, and promote their applications in water splitting, metal-air batteries, or other clean energy fields.

Cu-N Synergism Regulation to Enhance Anionic Redox Reversibility and Activity of Li- and Mn-Rich Layered Oxides Cathode.

Anionic redox chemistry enables extraordinary capacity for Li- and Mn-rich layered oxides (LMROs) cathodes. Unfortunately, irreversible surface oxygen evolution evokes the pernicious phase transition, structural deterioration, and severe electrode-electrolyte interface side reaction with element dissolution, resulting in fast capacity and voltage fading of LMROs during cycling and hindering its commercialization. Herein, a redox couple strategy is proposed by utilizing copper phthalocyanine (CuPc) to address the irreversibility of anionic redox. The Cu-N synergistic effect of CuPc could not only inhibit surface oxygen evolution by reducing the peroxide ion O2 2- back to lattice oxygen O2-, but also enhance the reaction activity and reversibility of anionic redox in bulk to achieve a higher capacity and cycling stability. Moreover, the CuPc strategy suppresses the interface side reaction and induces the forming of a uniform and robust LiF-rich cathode electrolyte, interphase (CEI) to significantly eliminate transition metal dissolution. As a result, the CuPc-enhanced LMRO cathode shows superb cycling performance with a capacity retention of 95.0% after 500 long-term cycles. This study sheds light on the great effect of N-based redox couple to regulate anionic redox behavior and promote the development of high energy density and high stability LMROs cathode.

Spatially resolved current density distribution in GaN-based flip-chip green mini-LEDs by microscopic hyperspectral imaging and modified two-level modeling.

A modified two-level model is proposed to study the spatially resolved current density distribution of GaN-based green miniaturized light-emitting diodes (mini-LEDs), combining with microscopic hyperspectral imaging. We found that the spatially resolved current density distribution reveals both the radiative and non-radiative recombination mappings, which can also be provided separately by this model. In addition, higher current density is not necessarily correlated with higher photon emission, especially for the regions around the electrode edges, where the high current density suggests current crowding and defect-related non-radiative recombination. The current density distribution of mini-LEDs is further verified by the laser-beam-induced current (LBIC) and the spatially resolved mappings of peak wavelength and FWHM. The modified two-level model also offers radiative/non-radiative mappings and is proved to be beneficial to determine the micro-zone current density distribution and to reveal the intrinsic radiative/non-radiative recombination mechanism of mini-LEDs.

An integrated model incorporating deep learning, hand-crafted radiomics and clinical and US features to diagnose central lymph node metastasis in patients with papillary thyroid cancer.

OBJECTIVE: To evaluate the value of an integrated model incorporating deep learning (DL), hand-crafted radiomics and clinical and US imaging features for diagnosing central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC). METHODS: This retrospective study reviewed 613 patients with clinicopathologically confirmed PTC from two institutions. The DL model and hand-crafted radiomics model were developed using primary lesion images and then integrated with clinical and US features selected by multivariate analysis to generate an integrated model. The performance was compared with junior and senior radiologists on the independent test set. SHapley Additive exPlanations (SHAP) plot and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the visualized explanation of the model. RESULTS: The integrated model yielded the best performance with an AUC of 0.841. surpassing that of the hand-crafted radiomics model (0.706, p < 0.001) and the DL model (0.819, p = 0.26). Compared to junior and senior radiologists, the integrated model reduced the missed CLNM rate from 57.89% and 44.74-27.63%, and decreased the rate of unnecessary central lymph node dissection (CLND) from 29.87% and 27.27-18.18%, respectively. SHAP analysis revealed that the DL features played a primary role in the diagnosis of CLNM, while clinical and US features (such as extrathyroidal extension, tumour size, age, gender, and multifocality) provided additional support. Grad-CAM indicated that the model exhibited a stronger focus on thyroid capsule in patients with CLNM. CONCLUSION: Integrated model can effectively decrease the incidence of missed CLNM and unnecessary CLND. The application of the integrated model can help improve the acceptance of AI-assisted US diagnosis among radiologists.

A bimodal nomogram as an adjunct tool to reduce unnecessary breast biopsy following discordant ultrasonic and mammographic BI-RADS assessment.

OBJECTIVE: To develop a bimodal nomogram to reduce unnecessary biopsies in breast lesions with discordant ultrasound (US) and mammography (MG) Breast Imaging Reporting and Data System (BI-RADS) assessments. METHODS: This retrospective study enrolled 706 women following opportunistic screening or diagnosis with discordant US and MG BI-RADS assessments (where one assessed a lesion as BI-RADS 4 or 5, while the other assessed the same lesion as BI-RADS 0, 2, or 3) from two medical centres between June 2019 and June 2021. Univariable and multivariable logistic regression analyses were used to develop the nomogram. DeLong's and McNemar's tests were used to assess the model's performance. RESULTS: Age, MG features (margin, shape, and density in masses, suspicious calcifications, and architectural distortion), and US features (margin and shape in masses as well as calcifications) were independent risk factors for breast cancer. The nomogram obtained an area under the curve of 0.87 (95% confidence interval (CI), 0.83-0.91), 0.91 (95% CI, 0.87 - 0.96), and 0.92 (95% CI, 0.86-0.98) in the training, internal validation, and external testing samples, respectively, and demonstrated consistency in calibration curves. Coupling the nomogram with US reduced unnecessary biopsies from 74 to 44% and the missed malignancies rate from 13 to 2%. Similarly, coupling with MG reduced missed malignancies from 20 to 6%, and 63% of patients avoided unnecessary biopsies. Interobserver agreement between US and MG increased from - 0.708 (poor agreement) to 0.700 (substantial agreement) with the nomogram. CONCLUSION: When US and MG BI-RADS assessments are discordant, incorporating the nomogram may improve the diagnostic accuracy, avoid unnecessary breast biopsies, and minimise missed diagnoses. CLINICAL RELEVANCE STATEMENT: The nomogram developed in this study could be used as a computer program to assist radiologists with detecting breast cancer and ensuring more precise management and improved treatment decisions for breast lesions with discordant assessments in clinical practice. KEY POINTS: • Coupling the nomogram with US and mammography improves the detection of breast cancers without the risk of unnecessary biopsy or missed malignancies. • The nomogram increases mammography and US interobserver agreement and enhances the consistency of decision-making. • The nomogram has the potential to be a computer program to assist radiologists in identifying breast cancer and making optimal decisions.

Synthesis of Spiro Polycyclic N-Heterocycles and Indolecarbazoles via Merging Oxidative Coupling and Cascade Palladium-Catalyzed Intramolecular Oxidative Cyclization.

We report a step-economic strategy for the direct synthesis of spiro polycyclic N-heterocycles and indolecarbazole-fused naphthoquinones by merging oxidative coupling and cascade palladium-catalyzed intramolecular oxidative cyclization. In the protocol, bi-indolylnaphthoquinones were first synthesized by oxidative coupling of indoles and naphthoquinones. Subsequent cascade palladium-catalyzed intramolecular oxidative cyclization of bi-indolylnaphthoquinones gave spiro polycyclic N-heterocycles and indolecarbazoles. The intramolecular oxidative cyclization approach could also be realized by the presence or absence of iron catalysts under standard conditions. This protocol is featured with moderate to excellent yields, a wide substrate scope, and divergent structures of products.

PI-RADS Version 2.0 Versus Version 2.1: Comparison of Prostate Cancer Gleason Grade Upgrade and Downgrade Rates From MRI-Targeted Biopsy to Radical Prostatectomy.

BACKGROUND. Precise risk stratification through MRI/ultrasound (US) fusion-guided targeted biopsy (TBx) can guide optimal prostate cancer (PCa) management. OBJECTIVE. The purpose of this study was to compare PI-RADS version 2.0 (v2.0) and PI-RADS version 2.1 (v2.1) in terms of the rates of International Society of Urological Pathology (ISUP) grade group (GG) upgrade and downgrade from TBx to radical prostatectomy (RP). METHODS. This study entailed a retrospective post hoc analysis of patients who underwent 3-T prostate MRI at a single institution from May 2015 to March 2023 as part of three prospective clinical trials. Trial participants who underwent MRI followed by MRI/US fusion-guided TBx and RP within a 1-year interval were identified. A single genitourinary radiologist performed clinical interpretations of the MRI examinations using PI-RADS v2.0 from May 2015 to March 2019 and PI-RADS v2.1 from April 2019 to March 2023. Upgrade and downgrade rates from TBx to RP were compared using chi-square tests. Clinically significant cancer was defined as ISUP GG2 or greater. RESULTS. The final analysis included 308 patients (median age, 65 years; median PSA density, 0.16 ng/mL2). The v2.0 group (n = 177) and v2.1 group (n = 131) showed no significant difference in terms of upgrade rate (29% vs 22%, respectively; p = .15), downgrade rate (19% vs 21%, p = .76), clinically significant upgrade rate (14% vs 10%, p = .27), or clinically significant downgrade rate (1% vs 1%, p > .99). The upgrade rate and downgrade rate were also not significantly different between the v2.0 and v2.1 groups when stratifying by index lesion PI-RADS category or index lesion zone, as well as when assessed only in patients without a prior PCa diagnosis (all p > .01). Among patients with GG2 or GG3 at RP (n = 121 for v2.0; n = 103 for v2.1), the concordance rate between TBx and RP was not significantly different between the v2.0 and v2.1 groups (53% vs 57%, p = .51). CONCLUSION. Upgrade and downgrade rates from TBx to RP were not significantly different between patients whose MRI examinations were clinically interpreted using v2.0 or v2.1. CLINICAL IMPACT. Implementation of the most recent PI-RADS update did not improve the incongruence in PCa grade assessment between TBx and surgery.