Interlayer engineering of Fe3GeTe2: From 3D superlattice to 2D monolayer.

The discoveries of ferromagnetism down to the atomically thin limit in van der Waals (vdW) crystals by mechanical exfoliation have enriched the family of magnetic thin films [C. Gong et al., Nature 546, 265-269 (2017) and B. Huang et al., Nature 546, 270-273 (2017)]. However, compared to the study of traditional magnetic thin films by physical deposition methods, the toolbox of the vdW crystals based on mechanical exfoliation and transfer suffers from low yield and ambient corrosion problem and now is facing new challenges to study magnetism. For example, the formation of magnetic superlattice is difficult in vdW crystals, which limits the study of the interlayer interaction in vdW crystals [M. Gibertini, M. Koperski, A. F. Morpurgo, K. S. Novoselov, Nat. Nanotechnol. 14, 408-419 (2019)]. Here, we report a strategy of interlayer engineering of the magnetic vdW crystal Fe3GeTe2 (FGT) by intercalating quaternary ammonium cations into the vdW spacing. Both three-dimensional (3D) vdW superlattice and two-dimensional (2D) vdW monolayer can be formed by using this method based on the amount of intercalant. On the one hand, the FGT superlattice shows a strong 3D critical behavior with a decreased coercivity and increased domain wall size, attributed to the co-engineering of the anisotropy, exchange interaction, and electron doping by intercalation. On the other hand, the 2D vdW few layers obtained by over-intercalation are capped with organic molecules from the bulk crystal, which not only enhances the ferromagnetic transition temperature (TC), but also substantially protects the thin samples from degradation, thus allowing the preparation of large-scale FGT ink in ambient environment.

Understanding the Coupling Mechanism of Intercalation and Conversion Hybrid Storage in Lithium-Graphite Anode.

Anodes with high capacity and long lifespan play an important role in the advanced batteries. However, none of the existing anodes can meet these two requirements simultaneously. Lithium (Li)-graphite composite anode presents great potential in balancing these two requirements. Herein, the working mechanism of Li-graphite composite anode is comprehensively investigated. The capacity decay features of the composite anode are different from those of Li ion intercalation in Li ion batteries and Li metal deposition in Li metal batteries. An intercalation and conversion hybrid storage mechanism are proposed by analyzing the capacity decay ratios in the composite anode with different initial specific capacities. The capacity decay models can be divided into four stages including Capacity Retention Stage, Relatively Independent Operation Stage, Intercalation & Conversion Coupling Stage, Pure Li Intercalation Stage. When the specific capacity is between 340 and 450 mAh g-1, its capacity decay ratio is between that of pure intercalation and conversion model. These results intensify the comprehensive understandings on the working principles in Li-graphite composite anode and present novel insights in the design of high-capacity and long-lifespan anode materials for the next-generation batteries.

Exploring Porous Flow Behavior of the Decomposed Gas from CH4 Hydrate in Clayey Sediments by Molecular Dynamics Simulation.

A fundamental understanding of the fluid flow mechanism during CH4 hydrate dissociation in nanoscale clayey sediments from the molecular perspective can provide invaluable information for macroscale natural gas hydrate (NGH) exploration. In this work, the fluid flow behaviors of the decomposed gas from CH4 hydrate within clayey nanopores under different temperature conditions are revealed by molecular dynamics (MD) simulation. The simulation results indicate that the key influencing factors of gas-water flow in nanoscale clayey sediments include the diffusion and the random migration of gas molecules. The influencing mechanisms of fluid flow in nanopores are closely related with the temperature conditions. Under a low temperature condition, the gas diffusion process is impeded by the secondary hydrate formation, leading to the decline in gas transport velocity within nanopores. However, it is still noteworthy that the gas-water fluid flow channels are not completely blocked by the occurrence of secondary hydrate. Under a high temperature condition, the significant phenomenon of water migration during gas flow is observed, which can be ascribed to the gas-liquid entrainment effect in nanopores of the clayey sediment. These results may provide valuable implications and fundamental evidence for improving gas production efficiency in future field tests of NGH exploitation in marine sediments.

Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib.

Chemotherapy remains the main approach conserving vision during the treatment of retinoblastoma, the most prevalent eye cancer in children. Unfortunately, the development of chemoresistance stands as the primary reason for treatment failure. Within this study, we showed that prolonged exposure to vincristine led to heightened expression of JAK1 and JAK2 in retinoblastoma cells, while the other members of the JAK family exhibited no such changes. Employing a genetic intervention, we demonstrated the efficacy of depleting either JAK1 or JAK2 in countering vincristine-resistant retinoblastoma cells. In addition, the dual depletion of both JAK1 and JAK2 produced a more potent inhibitory outcome compared to the depletion of either gene alone. We further demonstrated that ruxolitinib, a small molecular inhibitor of JAK1/2, effectively reduced viability and colony formation in vincristine-resistant retinoblastoma cells. It also acts synergistically with vincristine in retinoblastoma cells regardless of inherent cellular and genetic heterogeneity. The effectiveness of ruxolitinib as standalone treatment against chemoresistant retinoblastoma, as well as its combination with vincristine, was validated in multiple retinoblastoma mouse models. Importantly, mice exhibited favorable tolerance to ruxolitinib administration. We confirmed that the underlying mechanism of ruxolitinib's action in chemoresistant retinoblastoma cells is the inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. Our study reveals that the underlying mechanism driving ruxolitinib's impact on chemoresistant retinoblastoma cells is the inhibition of JAK/STAT signaling. This study reveals the contribution of JAK1/2 to the development of chemoresistance in retinoblastoma and underscores the effectiveness of targeting JAK1/2 as a strategy to sensitize retinoblastoma to chemotherapy.

Clinical characterization and long-term postoperative outcomes of retinoblastoma patients receiving enucleation and primary orbital implantation in early infancy: an observational study.

OBJECTIVES: To retrospectively investigate clinical characterization and the long-term postoperative outcomes of retinoblastoma (RB) patients receiving enucleation with primary orbital implantation in early infancy (0-6 months old). METHODS: The clinical and follow-up data of 42 RB patients receiving enucleation with primary orbital implantation in early infancy at Beijing Tongren Hospital from December 2009 to January 2020 were analysed. The average follow-up time was 83 months. The patient group included 24 males and 18 females, 30 unilateral and 12 bilateral cases. A total of 44 eyes with 10 in stage D and 34 in stage E underwent 40 unilateral and 2 bilateral surgeries. 17 RB eyes received hydrogel and 27 RB eyes received hydroxyapatite implants. This study was performed by following the guideline of STROBE. RESULTS: Enucleation combined with primary orbital implantation promoted survival and was safe with few and minor complications such as increased secretion, upper eyelid ptosis, and sunken eye sockets which were not affected by stages, lateralities, or implant materials. 55-80% RB patients exhibited satisfactory appearance and obvious or moderate motility of orbital implants according to the evaluation by doctors and family members. Family members were likely more optimistic about the appearance and more pessimistic about motility of the orbital implantation than doctors did.The quality of life was high as indicated by PedsQL3.0 or PedsQL4.0 scores ( ≧ 90 for > 75% patients). It was not affected by the stages, laterality, and implant materials, nor affected by the appearance and motility of the implants. CONCLUSIONS: The outcomes of the combination of enucleation and primary orbital implantation for pertinent RB patients in early infancy are generally satisfactory with few and minor complications, high safety, appearance, and overall quality of life. Enucleation combined with primary orbital implantation in early infancy benefits pertinent RB patients in appearance, survival, and quality of life.

[Zhongfeng Xingnao Decoction alleviates intracerebral haemorrhage-induced brain injury via inhibiting neuronal ferroptosis].

Zhongfeng Xingnao Decoction(ZFXN) has been utilized for treating intracerebral hemorrhage(ICH) in China, while the pharmacological mechanism of ZFXN remains unclear. Exploring the pharmacological roles of ZFXN is critical for guiding the treatment of cerebrovascular diseases. In this study, a rat model of ICH was constructed by injection of Ⅶ collagenase in the right caudate nucleus. SD rats were randomly assigned into five groups, and the neurological function of rats was evaluated based on the Bederson score. Magnetic resonance imaging(MRI) was used to assess the volume of ICH. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were employed to observe the pathological and ultrastructural changes in the brain tissue. The levels of reactive oxygen species(ROS) were measured by flow cytometry. The immunofluorescence assay was employed to detect the expression of glutathione peroxidase 4(GPX4) in neurons surrounding the hematoma. Finally, Western blot was employed to determine the expression of ferroptosis-related proteins upstream frameshift 1(UPF1), ferroportin(FPN), acyl-CoA ligase 4(ACSL4), cyclooxyge-nase-2(COX-2), GPX4, NADPH oxidase 1(NOX1), and solute carrier family 7 member 11(SLC7A11) after ICH. Compared with the model(ICH) group, ZFXN treatment for 5 days attenuated neurological dysfunction, reduced the hematoma volume, and alleviated the pathological changes induced by ICH. Meanwhile, ZFXN lowered the levels of Fe~(2+) and oxidative stress and up-regulated the expression of proteins inhibiting ferroptosis. ZFXN improved the prognosis of ICH in rats by inhibiting neuronal ferroptosis, which provided a valuable guide for the clinical application of ZFXN. ZFXN may inhibit ferroptosis by promoting the expression of SLC7A11 and FPN.

Structure-guided antibody cocktail for prevention and treatment of COVID-19.

Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed host immunity. Here, we report the generation and characterization of a series of chimeric antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Some of these antibodies exhibit exceptionally potent neutralization activities in vitro and in vivo, and the most potent of our antibodies target three distinct non-overlapping epitopes within the RBD. Cryo-electron microscopy analyses of two highly potent antibodies in complex with the SARS-CoV-2 spike protein suggested they may be particularly useful when combined in a cocktail therapy. The efficacy of this antibody cocktail was confirmed in SARS-CoV-2-infected mouse and hamster models as prophylactic and post-infection treatments. With the emergence of more contagious variants of SARS-CoV-2, cocktail antibody therapies hold great promise to control disease and prevent drug resistance.

Generative adversarial network-based deep learning approach in classification of retinal conditions with optical coherence tomography images.

PURPOSE: To determine whether a deep learning approach using generative adversarial networks (GANs) is beneficial for the classification of retinal conditions with Optical coherence tomography (OCT) images. METHODS: Our study utilized 84,452 retinal OCT images obtained from a publicly available dataset (Kermany Dataset). Employing GAN, synthetic OCT images are produced to balance classes of retinal disorders. A deep learning classification model is constructed using pretrained deep neural networks (DNNs), and outcomes are evaluated using 2082 images collected from patients who visited the Department of Ophthalmology and the Department of Endocrinology and Metabolism at the Tri-service General Hospital in Taipei from January 2017 to December 2021. RESULTS: The highest classification accuracies accomplished by deep learning machines trained on the unbalanced dataset for its training set, validation set, fivefold cross validation (CV), Kermany test set, and TSGH test set were 97.73%, 96.51%, 97.14%, 99.59%, and 81.03%, respectively. The highest classification accuracies accomplished by deep learning machines trained on the synthesis-balanced dataset for its training set, validation set, fivefold CV, Kermany test set, and TSGH test set were 98.60%, 98.41%, 98.52%, 99.38%, and 84.92%, respectively. In comparing the highest accuracies, deep learning machines trained on the synthesis-balanced dataset outperformed deep learning machines trained on the unbalanced dataset for the training set, validation set, fivefold CV, and TSGH test set. CONCLUSIONS: Overall, deep learning machines on a synthesis-balanced dataset demonstrated to be advantageous over deep learning machines trained on an unbalanced dataset for the classification of retinal conditions.

Total flavonoid extract from Dracocephalum moldavica L. improves pulmonary fibrosis by reducing inflammation and inhibiting the hedgehog signaling pathway.

Dracocephalum Moldavica L. is a traditional herb for improving pharynx and relieving cough. However, the effect on pulmonary fibrosis is not clear. In this study, we explored the impact and molecular mechanism of total flavonoid extract from Dracocephalum moldavica L. (TFDM) on bleomycin-induced pulmonary fibrosis mouse model. Lung function testing, lung inflammation and fibrosis, and the related factors were detected by the lung function analysis system, HE and Masson staining, ELISA, respectively. The expression of proteins was studied through Western Blot, immunohistochemistry, and immunofluorescence while the expression of genes was analyzed by RT-PCR. The results showed that TFDM significantly improved lung function in mice, reduced the content of inflammatory factors, thereby reducing the inflammation. It was found that expression of collagen type I, fibronectin, and α-smooth muscle actin was significantly decreased by TFDM. The results further showed that TFDM interferes with hedgehog signaling pathway by decreasing the expression of Shh, Ptch1, and SMO proteins and thereby inhibiting the generation of downstream target gene Gli1 and thus improving pulmonary fibrosis. Conclusively, these findings suggest that TFDM improve pulmonary fibrosis by reducing inflammation and inhibition of the hedgehog signaling pathway.

Calycosin protects against oxidative stress-induced cardiomyocyte apoptosis by activating aldehyde dehydrogenase 2.

Myocardial infarction (MI) is the leading cause of death worldwide, and oxidative stress is part of the process that causes MI. Calycosin, a naturally occurring substance with cardioprotective properties, is one of the major active constituents in Radix Astragali. In this study, effect of Calycosin was investigated in vivo and in vitro to determine whether it could alleviate oxidative stress and oxidative stress-induced cardiac apoptosis in neonatal cardiomyocytes (NCMs) via activation of aldehyde dehydrogenase 2 (ALDH2). Calycosin protected against oxidative stress and oxidative stress-induced apoptosis in NCMs. Molecular docking revealed that the ALDH2-Calycosin complex had a binding energy of -9.885 kcal/mol. In addition, molecular docking simulations demonstrated that the ALDH2-Calycosin complex was stable. Using BLI assays, we confirmed that Calycosin could interact with ALDH2 (KD  = 1.9 × 10-4 M). Furthermore, an ALDH2 kinase activity test revealed that Calycosin increased ALDH2 activity, exhibiting an EC50 of 91.79 µM. Pre-incubation with ALDH2 inhibitor (CVT-10216 or disulfiram) reduced the cardio-protective properties Calycosin. In mice with MI, Calycosin therapy substantially reduced myocardial apoptosis, oxidative stress, and activated ALDH2. Collectively, our findings clearly suggest that Calycosin reduces oxidative stress and oxidative stress-induced apoptosis via the regulation of ALDH2 signaling, which supports potential therapeutic use in MI.

ASARA, a prediction model based on Child-Pugh class in hepatocellular carcinoma patients undergoing transarterial chemoembolization.

BACKGROUND: Due to the high heterogeneity among hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE), the prognosis of patients varies significantly. The decision-making on the initiation and/or repetition of TACE under different liver functions is a matter of concern in clinical practice. Thus, we aimed to develop a prediction model for TACE candidates using risk stratification based on varied liver function. METHODS: A total of 222 unresectable HCC patients who underwent TACE as their only treatment were included in this study. Cox proportional hazards regression was performed to select the independent risk factors and establish a predictive model for the overall survival (OS). The model was validated in patients with different Child-Pugh class and compared to previous TACE scoring systems. RESULTS: The five independent risk factors, including alpha-fetoprotein (AFP) level, maximal tumor size, the increase of albumin-bilirubin (ALBI) grade score, tumor response, and the increase of aspartate aminotransferase (AST), were used to build a prognostic model (ASARA). In the training and validation cohorts, the OS of patients with ASARA score ≤ 2 was significantly higher than that of patients with ASARA score > 2 (P < 0.001, P = 0.006, respectively). The ASARA model and its modified version "AS(ARA)" can effectively distinguish the OS (P < 0.001, P = 0.004) between patients with Child-Pugh class A and B, and the C-index was 0.687 and 0.706, respectively. For repeated TACE, the ASARA model was superior to Assessment for Retreatment with TACE (ART) and ALBI grade, maximal tumor size, AFP, and tumor response (ASAR) among Child-Pugh class A patients. For the first TACE, the performance of AS(ARA) was better than that of modified hepatoma arterial-embolization prognostic (mHAP), mHAP3, and ASA(R) models among Child-Pugh class B patients. CONCLUSIONS: The ASARA scoring system is valuable in the decision-making of TACE repetition for HCC patients, especially Child-Pugh class A patients. The modified AS(ARA) can be used to screen the ideal candidate for TACE initiation in Child-Pugh class B patients with poor liver function.

Comparison of Endoscopic Dacryocystorhinostomy Outcomes With or Without Bicanalicular Silicone Tube Intubation in Acquired Lacrimal Sac Mucocele.

PURPOSE: This paper was established to validate the necessity of bicanalicular silicone tube intubation (BSTI) in patients with acquired lacrimal sac mucocele (ALSM) receiving endoscopic dacryocystorhinostomy (DCR). METHODS: In total, 92 patients (92 eyes) diagnosed with ALSM undergone endoscopic DCR from November 2016 to December 2021 were recruited for our research. Patients were allocated into 2 equal treatment groups: group A (patients undergoing BSTI) and group B (patients not receiving this procedure). The tubes were removed 2 months postoperation in group A. Surgical outcomes and related complications were evaluated 12 months postoperation. RESULTS: Ultimately, this study included 83 patients with ALSM, consisting of 43 patients in group A and 40 patients in group B. All patients exhibited notable mass shrinkage with the opening of the lacrimal sac during the surgery and the swelling in the lacrimal sac area was completely relieved within 5 days postoperation. At the 12-month follow-up, no distinct difference was observed in the anatomic success rate between the 2 groups (group A: 93.0%; group B: 90.0%) ( t = 0.010, P > 0.05). However, patients in group A presented higher functional success rates (90.7%) in contrast to those patients in group B (72.5%) ( t = 4.635, P < 0.05). In both groups, the failure of the lacrimal passage reconstruction was attributed to granulation tissue formation or scar formation at the ostium. No sac mucocele recurrence occurred during the follow-up. CONCLUSION: Endoscopic DCR treatment for ALSM achieves satisfactory postoperative effects without recurrence, and BSTI may improve the functional success rate.

Dexmedetomidine alleviates acute lung injury by promoting Tregs differentiation via activation of AMPK/SIRT1 pathway.

OBJECTIVES: To explore the anti-inflammatory effect and the potential mechanism of dexmedetomidine in ARDS/ALI. MATERIALS AND METHODS: C57BL/6 mice and EL-4 cells were used in this research. The ALI model was established by CLP. The level of inflammatory cytokines in the lung and blood, the severity of lung injury, the expression of Foxp3, and the proportion of Tregs were detected before and after dexmedetomidine treatment. The expression of the AMPK/SIRT1 after dexmedetomidine treatment was detected in vivo and in vitro. After blocking the AMPK/SIRT1 pathway or depleting Tregs in vivo, the level of the inflammatory response, tissue injury, and Tregs differentiation were detected again to clarify the effect of dexmedetomidine. RESULTS: Dexmedetomidine significantly reduced systemic inflammation and lung injury in CLP mice. Dexmedetomidine enhanced the Foxp3 expression in the lungs and the frequency of Tregs in the spleen. Dexmedetomidine up-regulated the protein expression of p-AMPK and SIRT1 in lungs and EL-4 cells and facilitated the differentiation of naïve CD4+ T cells into Tregs in vitro. Meanwhile, DEX also increased the expression of Helios in Treg cells. CONCLUSIONS: DEX could improve ARDS/ALI by facilitating the differentiation of Tregs from naïve CD4+ T cells via activating the AMPK/SIRT1 pathway.

Mosaic CuI -CuII -InIII 2D Perovskites: Pressure-Dependence of the Intervalence Charge Transfer and a Mechanochemical Alloying Method.

The perovskite (BA)4 [CuII (CuI InIII )0.5 ]Cl8 (1BA ; BA+ =butylammonium) allows us to study the high-pressure structural, optical, and transport properties of a mixed-valence 2D perovskite. Compressing 1BA reduces the onset energy of CuI/II intervalence charge transfer from 1.2 eV at ambient pressure to 0.2 eV at 21 GPa. The electronic conductivity of 1BA increases by 4 orders of magnitude upon compression to 20 GPa, when the activation energy for conduction decreases to 0.16 eV. In contrast, CuII perovskites achieve similar conductivity at ≈50 GPa. The solution-state synthesis of these perovskites is complicated, with more undesirable side products likely from the precursor mixtures containing three different metal ions. To circumvent this problem, we demonstrate an efficient mechanochemical synthesis to expand this family of halide perovskites with complex composition by simply pulverizing together powders of 2D CuII single perovskites and CuI InIII double perovskites.

Multistate Aggregation-Induced Chiroptical Properties of Enantiopure Disulfide-Mediated Bispyrene Macrocycles.

A chiral bispyrene macrocycle designed for exclusive intermolecular excimer fluorescence upon aggregation was synthesized by a double hydrothiolation of a bis-enol ether macrocycle followed by intramolecular oxidation of free thiols. Unusually high stereoselectivity was achieved for the thiol-ene additions under templated conditions and Et3 B/O2 radical initiation. After enantiomer separation (chiral stationary phase HPLC), aqueous conditions provoked aggregation. Detailed structural evolution was afforded by ECD/CPL monitoring. Three regimes can be observed and characterized by strong modifications in chiroptical patterns under, at, or above a 70 % H2 O : THF threshold. In luminescence, high glum dissymmetry factors values were obtained, up to 0.022, as well as a double sign inversion of CPL signals during the aggregation, a behavior rationalized by time-dependent density functional theory (TDDFT) calculations. Langmuir layers of enantiopure disulfide macrocycles were formed at the air-water interface and transferred onto solid substrates to afford Langmuir-Blodgett films, which were then studied by AFM and UV/ECD/fluorescence/CPL.

Using machine learning to determine the correlation between physiological and environmental parameters and the induction of acute mountain sickness.

BACKGROUND: Recent studies on acute mountain sickness (AMS) have used fixed-location and fixed-time measurements of environmental and physiological variable to determine the influence of AMS-associated factors in the human body. This study aims to measure, in real time, environmental conditions and physiological variables of participants in high-altitude regions to develop an AMS risk evaluation model to forecast prospective development of AMS so its onset can be prevented. RESULTS: Thirty-two participants were recruited, namely 25 men and 7 women, and they hiked from Cuifeng Mountain Forest Park parking lot (altitude: 2300 m) to Wuling (altitude: 3275 m). Regression and classification machine learning analyses were performed on physiological and environmental data, and Lake Louise Acute Mountain Sickness Scores (LLS) to establish an algorithm for AMS risk analysis. The individual R2 coefficients of determination between the LLS and the measured altitude, ambient temperature, atmospheric pressure, relative humidity, climbing speed, heart rate, blood oxygen saturation (SpO2), heart rate variability (HRV), were 0.1, 0.23, 0, 0.24, 0, 0.24, 0.27, and 0.35 respectively; incorporating all aforementioned variables, the R2 coefficient is 0.62. The bagged trees classifier achieved favorable classification results, yielding a model sensitivity, specificity, accuracy, and area under receiver operating characteristic curve of 0.999, 0.994, 0.998, and 1, respectively. CONCLUSION: The experiment results indicate the use of machine learning multivariate analysis have higher AMS prediction accuracies than analyses utilizing single varieties. The developed AMS evaluation model can serve as a reference for the future development of wearable devices capable of providing timely warnings of AMS risks to hikers.

Optical Activity from Anisotropic-Nanocluster-Assembled Supercrystals in Achiral Crystallographic Point Groups.

Accomplishing optical activity in achiral materials has long been a challenge. Achiral nanomaterials that crystallize in achiral point groups are generally optically inactive. Herein we report the surprising observation of optical activity in several achiral point groups for supercrystals assembled from anisotropic metal nanoclusters with atomic precision. By analyzing multiple achiral nanoclusters with different molecular structures and symmetry space groups, we have identified that the molecular anisotropy of nanocluster entities and their asymmetric arrangement in point groups of supercrystals are the two key factors for the realization of optical activity in such supercrystals. We have further exploited the polarization effect of the nanocluster supercrystals as a polarization switch that can alter the polarized state of the linearly polarized light. Our findings have broadened the fundamental principles for producing nanomaterial-based optical activity and devices with polarization effects.

Quasi-One-Dimensional Metallicity in Compressed CsSnI3.

Low-dimensional metal halides exhibit strong structural and electronic anisotropies, making them candidates for accessing unusual electronic properties. Here, we demonstrate pressure-induced quasi-one-dimensional (quasi-1D) metallicity in δ-CsSnI3. With the application of pressure up to 40 GPa, the initially insulating δ-CsSnI3 transforms to a metallic state. Synchrotron X-ray diffraction and Raman spectroscopy indicate that the starting 1D chain structure of edge-sharing Sn-I octahedra in δ-CsSnI3 is maintained in the high-pressure metallic phase while the SnI6 octahedral chains are distorted. Our experiments combined with first-principles density functional theory calculations reveal that pressure induces Sn-Sn hybridization and enhances Sn-I coupling within the chain, leading to band gap closure and formation of conductive SnI6 distorted octahedral chains. In contrast, the interchain I...I interactions remain minimal, resulting in a highly anisotropic electronic structure and quasi-1D metallicity. Our study offers a high-pressure approach for achieving diverse electronic platforms in the broad family of low-dimensional metal halides.

A Multicenter Randomized Controlled Study of Contrast-enhanced US versus US-guided Biopsy of Focal Liver Lesions.

Background Retrospective or single-center prospective studies with relatively small samples have shown that contrast-enhanced US (CEUS) can improve the diagnostic accuracy of percutaneous biopsy, but larger prospective studies are lacking. Purpose To assess the diagnostic performance of CEUS-guided biopsy (CEUS-GB) of focal liver lesions (FLLs) compared with US-guided biopsy (US-GB) in a prospective multicenter study. Materials and Methods In this randomized controlled study conducted in nine hospitals in China between March 2016 and August 2019, adult participants with FLLs detected with US, CT, or MRI and planned for percutaneous biopsy were randomly assigned to undergo either US-GB or CEUS-GB. Lesions diagnosed as malignant at histopathologic analysis were considered true-positive findings. Benign or indeterminate lesions required further confirmation with either repeat biopsy or clinical follow-up at 6 months or later. The primary endpoint was the diagnostic accuracy rate, and comparison between groups was made using the χ2 test. Results In this study, 2056 participants (1297 men, 759 women; mean age, 58 years ± 11 [SD]) were analyzed: 1030 underwent biopsy with US guidance and 1026 underwent biopsy with CEUS guidance. The overall diagnostic accuracy rate of CEUS-GB was 96% (983 of 1026) versus 93% (953 of 1030) for US-GB (P = .002), CEUS-GB enabled correct identification in 96% of participants (983 of 1026) compared with 92% (953 of 1030) with US-GB (P = .002). The negative predictive value (NPV) for both biopsy methods was moderate but significantly higher for CEUS-GB than for US-GB (74% vs 57%, P = .001). The difference was remarkable for lesions smaller than 2.0 cm, with CEUS-GB showing higher diagnostic accuracy (96% vs 88%, P = .004) and sensitivity (95% vs 87%, P = .007) than US-GB. Among lesions smaller than 2.0 cm, the accuracy of CEUS-GB and US-GB for detection of hepatocellular carcinoma was 93% and 80%, respectively (P = .008), while it was comparable for liver metastases (98% vs 95%, P = .63). Conclusion Contrast-enhanced US-guided biopsy of focal liver lesions is an effective and safe procedure with a higher diagnostic accuracy than US-guided biopsy, especially for lesions smaller than 2.0 cm and for hepatocellular carcinoma diagnosis. Clinical trial registration no. NCT02413437 © RSNA, 2022 Online supplemental material is available for this article.

OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis.

BACKGROUND: Obg-like ATPase 1 (OLA1) is a highly conserved GTPase, which was over expressed in a variety of malignant tumors, but its role in colorectal cancer (CRC) was poorly studied. PATIENTS AND METHODS: Three public CRC gene databases were applied for OLA1 mRNA expression detection. The clinical data of 111 CRC patients were retrospectively collected from the Second Affiliated Hospital of Zhejiang University (SAHZU) for OLA1 protein expression and Kaplan-Meier Survival analysis. OLA1 stably knocked out CRC cell lines were conducted by CRISPR-Cas9 for experiments in vitro and in vivo. RESULTS: OLA1 was highly expressed in 84% CRC compared to matched surrounding tissues. Patients with OLA1 high expression had a significantly lower 5-year survival rate (47%) than those with OLA1 low expression (75%). OLA1 high expression was an independent factor of poor prognosis in CRC patients. OLA1-KO CRC cell lines showed lower ability of growth and tumorigenesis in vitro and in vivo. By mRNA sequence analysis, we found 113 differential express genes in OLA1-KO cell lines, of which 63 were hypoxic related. HIF1α was a key molecule in hypoxic regulation. Further molecular mechanisms showed HIF1α /CA9 mRNA and/or protein levels were heavily downregulated in OLA1-KO cell lines, which could explain the impaired tumorigenesis. According to previous studies, HIF1α was a downstream gene of GSK3ß, we verified GSK3ß was over-activated in OLA1-KO cell lines. CONCLUSION: OLA1 was a new gene that was associated with carcinogenesis and poor outcomes in CRC by activation of HIF1α/CA9 axis, which may be interpreted by GSK3ß.