Transcatheter Arterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND/AIMS:  In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS:  Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. RESULTS:  The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. CONCLUSION:  In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.

Mitigation of Gilbert Damping in the CoFe/CuOx Orbital Torque System.

Charge-spin interconversion processes underpin the generation of spin-orbit torques in magnetic/nonmagnetic bilayers. However, efficient sources of spin currents such as 5d metals are also efficient spin sinks, resulting in a large increase of magnetic damping. Here we show that a partially oxidized 3d metal can generate a strong orbital torque without a significant increase in damping. Measurements of the torque efficiency ξ and Gilbert damping α in CoFe/CuOx and CoFe/Pt indicate that ξ is comparable in the two systems. The increase in damping relative to a single CoFe layer is Δα < 0.002 in CoFe/CuOx and Δα ≈ 0.005-0.02 in CoFe/Pt, depending on CoFe thickness. We ascribe the nonreciprocal relationship between Δα and ξ in CoFe/CuOx to the small orbital-spin current ratio generated by magnetic resonance in CoFe and the lack of an efficient spin sink in CuOx. Our findings provide new perspectives on the efficient excitation of magnetization dynamics via the orbital torque.

Transcatheter Arterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.

Learned Full Waveform Inversion Incorporating Task Information for Ultrasound Computed Tomography.

Ultrasound computed tomography (USCT) is an emerging imaging modality that holds great promise for breast imaging. Full-waveform inversion (FWI)-based image reconstruction methods incorporate accurate wave physics to produce high spatial resolution quantitative images of speed of sound or other acoustic properties of the breast tissues from USCT measurement data. However, the high computational cost of FWI reconstruction represents a significant burden for its widespread application in a clinical setting. The research reported here investigates the use of a convolutional neural network (CNN) to learn a mapping from USCT waveform data to speed of sound estimates. The CNN was trained using a supervised approach with a task-informed loss function aiming at preserving features of the image that are relevant to the detection of lesions. A large set of anatomically and physiologically realistic numerical breast phantoms (NBPs) and corresponding simulated USCT measurements was employed during training. Once trained, the CNN can perform real-time FWI image reconstruction from USCT waveform data. The performance of the proposed method was assessed and compared against FWI using a hold-out sample of 41 NBPs and corresponding USCT data. Accuracy was measured using relative mean square error (RMSE), structural self-similarity index measure (SSIM), and lesion detection performance (DICE score). This numerical experiment demonstrates that a supervised learning model can achieve accuracy comparable to FWI in terms of RMSE and SSIM, and better performance in terms of task performance, while significantly reducing computational time.

Chitosan-based high-performance flexible supercapacitor via "in-situ co-doping/self-regulation-activation" strategy.

The construction of N, P co-doped hierarchically porous carbons (NPHPC) by a facile and green approach is crucial for high-performance energy storage but still an enormous challenge. Herein, an environment-friendly "in-situ co-doping, self-regulation-activation" strategy is presented to one-pot synthesize NPHPC using a phytic acid-induced polyethyleneimine/chitosan gel (PEI-PA-CS) as single precursor. NPHPC displayed a specific surface area of up to 1494 m2 g-1, high specific capacitance of 449 F g-1 at 1 A g-1, outstanding rate capability and cycling durability in a wide temperature range (-20 to 60 °C). NPHPC and PEI-PA-CS electrolyte assembled symmetric quasi-solid-state flexible supercapacitor presents superb energy outputs of 27.06 Wh kg-1 at power density of 225 W kg-1. For capacitive deionization (CDI), NPHPC also exhibit an excellent salt adsorption capacity of 16.54 mg g-1 in 500 mg L-1 NaCl solution at a voltage of 1.4 V, and regeneration performance. This study provides a valuable reference for the rational design and synthesis of novel biomass-derived energy-storage materials by integrating phytic acid induced heteroatom doping and pore engineering.

B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1.

Introduction: BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as on several other substrates. BAP1 is also a highly important tumor suppressor, expressed and functional across many cell types and tissues. In recent work, we demonstrated a cell intrinsic role of BAP1 in the B cell lineage development in murine bone marrow, however the role of BAP1 in the regulation of B cell mediated humoral immune response has not been previously explored. Methods and results: In the current study, we demonstrate that a B-cell intrinsic loss of BAP1 in activated B cells in the Bap1 fl/fl Cγ1-cre murine model results in a severe defect in antibody production, with altered dynamics of germinal centre B cell, memory B cell, and plasma cell numbers. At the cellular and molecular level, BAP1 was dispensable for B cell immunoglobulin class switching but resulted in an impaired proliferation of activated B cells, with genome-wide dysregulation in histone H2AK119ub levels and gene expression. Conclusion and discussion: In summary, our study establishes the B-cell intrinsic role of BAP1 in antibody mediated immune response and indicates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of B cell activation and humoral immunity.

The Potential Regulation of Working Anode for Long-Term Zero-Volt Storage at 37 °C in Li-Ion Batteries.

The advanced lithium-ion batteries that can tolerate zero-volt storage (ZVS) are in high demand for implantable medical devices and spacecraft. However, ZVS can raise the anode potential, leading to Cu current collector dissolution and solid-electrolyte interphase (SEI) degradation, especially at 37 °C. In this contribution, by quantitatively regulating the dosage of Li6CoO4 cathode additives, controllable potential of the working anode under abusive-discharge conditions is demonstrated. The addition of Li6CoO4 keeps zero-crossing potential (ZCP) and the potential of ZVS below 2.0 V (vs Li/Li+) for LiCoO2|mesocarbon microbead cells at 37 °C. The capacity retention ratio (CRR) increases from 69.1% and 35.9% to 98.6% and 90.8% after 10 and 20 days of ZVS, respectively. The Cu dissolution and SEI degradation are effectively suppressed, while the over-lithiated cathode exhibits high reversible capacity after ZVS. The limiting conditions of long-term ZVS are further explored and a corresponding guide map is designed. When quantitatively regulating ZCP and the potential in ZVS, Cu dissolution, SEI degradation, and irreversible conversion of the cathode constitute the limiting conditions. This contribution designs the most reasonable potential range for ZVS protection at 37 °C, and realizes the best CRR record through precise potential regulation for the first time.

Chromatin-binding deubiquitinase MYSM1 acts in haematopoietic progenitors to control dendritic cell development and to program dendritic cell responses to microbial stimulation.

Dendritic cells (DCs) are the most significant antigen presenting cells of the immune system, critical for the activation of naïve T cells. The pathways controlling DC development, maturation, and effector function therefore require precise regulation to allow for an effective induction of adaptive immune response. MYSM1 is a chromatin binding deubiquitinase (DUB) and an activator of gene expression via its catalytic activity for monoubiquitinated histone H2A (H2A-K119ub), which is a highly abundant repressive epigenetic mark. MYSM1 is an important regulator of haematopoiesis in mouse and human, and a systemic constitutive loss of Mysm1 in mice results in a depletion of many haematopoietic progenitors, including DC precursors, with the downstream loss of most DC lineage cells. However, the roles of MYSM1 at the later checkpoints in DC development, maturation, activation, and effector function at present remain unknown. In the current work, using a range of novel mouse models (Mysm1flCreERT2, Mysm1flCD11c-cre, Mysm1DN), we further the understanding of MYSM1 functions in the DC lineage: assessing the requirement for MYSM1 in DC development independently of other complex developmental phenotypes, exploring its role at the later checkpoints in DC maintenance and activation in response to microbial stimulation, and testing the requirement for the DUB catalytic activity of MYSM1 in these processes. Surprisingly, we demonstrate that MYSM1 expression and catalytic activity in DCs are dispensable for the maintenance of DC numbers in vivo or for DC activation in response to microbial stimulation. In contrast, MYSM1 acts via its DUB catalytic activity specifically in haematopoietic progenitors to allow normal DC lineage development, and its loss results not only in a severe DC depletion but also in the production of functionally altered DCs, with a dysregulation of many housekeeping transcriptional programs and significantly altered responses to microbial stimulation.

Phalaenopsiszhanhouana (Orchidaceae, Vandeae), a new species from Yunnan, China.

A new species of Orchidaceae, Phalaenopsiszhanhouana, from Xichou County, Yunnan, China, is described and illustrated. The novelty is close to P.taenialis, P.wilsonii, and P.stobartiana, but differs from them by having a distinct, fleshy anterior callus with a deeply lobed apex at the base of the labellum and lateral lobes of labellum reflexed and facing outward.

Identification of arnicolide C as a novel chemosensitizer to suppress mTOR/E2F1/FANCD2 axis in non-small cell lung cancer.

BACKGROUND AND PURPOSE: The mammalian target of rapamycin (mTOR) pathway plays critical roles in intrinsic chemoresistance by regulating Fanconi anaemia complementation group D2 (FANCD2) expression. However, the mechanisms by which mTOR regulates FANCD2 expression and related inhibitors are not clearly elucidated. Extracts of Centipeda minima (C. minima) showed promising chemosensitizing effects by inhibiting FANCD2 activity. Here, we have aimed to identify the bioactive chemosensitizer in C. minima extracts and elucidate its underlying mechanism. EXPERIMENTAL APPROACH: The chemosensitizing effects of arnicolide C (ArC), a bioactive compound in C. minima, on non-small cell lung cancer (NSCLC) were investigated using immunoblotting, immunofluorescence, flow cytometry, the comet assay, small interfering RNA (siRNA) transfection and animal models. The online SynergyFinder software was used to determine the synergistic effects of ArC and chemotherapeutic drugs on NSCLC cells. KEY RESULTS: ArC had synergistic cytotoxic effects with DNA cross-linking drugs such as cisplatin and mitomycin C in NSCLC cells. ArC treatment markedly decreased FANCD2 expression in NSCLC cells, thus attenuating cisplatin-induced FANCD2 nuclear foci formation, leading to DNA damage and apoptosis. ArC inhibited the mTOR pathway and attenuated mTOR-mediated expression of E2F1, a critical transcription factor of FANCD2. Co-administration of ArC and cisplatin exerted synergistic anticancer effects in the A549 xenograft mouse model by suppressing mTOR/FANCD2 signalling in tumour tissues. CONCLUSION AND IMPLICATIONS: ArC suppressed DNA cross-linking drug-induced DNA damage response by inhibiting the mTOR/E2F1/FANCD2 signalling axis, serving as a chemosensitizing agent. This provides insight into the anticancer mechanisms of ArC and offers a potential combinatorial anticancer therapeutic strategy.

Erratum: Orbital Hanle Magnetoresistance in a 3d Transition Metal [Phys. Rev. Lett. 131, 156703 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.131.156703.

Orbital Hanle Magnetoresistance in a 3d Transition Metal.

The Hanle magnetoresistance is a telltale signature of spin precession in nonmagnetic conductors, in which strong spin-orbit coupling generates edge spin accumulation via the spin Hall effect. Here, we report the existence of a large Hanle magnetoresistance in single layers of Mn with weak spin-orbit coupling, which we attribute to the orbital Hall effect. The simultaneous observation of a sizable Hanle magnetoresistance and vanishing small spin Hall magnetoresistance in BiYIG/Mn bilayers corroborates the orbital origin of both effects. We estimate an orbital Hall angle of 0.016, an orbital relaxation time of 2 ps and diffusion length of the order of 2 nm in disordered Mn. Our findings indicate that current-induced orbital moments are responsible for magnetoresistance effects comparable to or even larger than those determined by spin moments, and provide a tool to investigate nonequilibrium orbital transport phenomena.

Focalizing regions of biomarker relevance facilitates biomarker prediction on histopathological images.

Image-based AI has thrived as a potentially revolutionary tool for predicting molecular biomarker statuses, which aids in categorizing patients for appropriate medical treatments. However, many methods using hematoxylin and eosin-stained (H&E) whole-slide images (WSIs) have been found to be inefficient because of the presence of numerous uninformative or irrelevant image patches. In this study, we introduced the region of biomarker relevance (ROB) concept to identify the morphological areas most closely associated with biomarkers for accurate status prediction. We actualized this concept within a framework called saliency ROB search (SRS) to enable efficient and effective predictions. By evaluating various lung adenocarcinoma (LUAD) biomarkers, we showcased the superior performance of SRS compared to current state-of-the-art AI approaches. These findings suggest that AI tools, built on the ROB concept, can achieve enhanced molecular biomarker prediction accuracy from pathological images.

Learned Full Waveform Inversion Incorporating Task Information for Ultrasound Computed Tomography.

Ultrasound computed tomography (USCT) is an emerging imaging modality that holds great promise for breast imaging. Full-waveform inversion (FWI)-based image reconstruction methods incorporate accurate wave physics to produce high spatial resolution quantitative images of speed of sound or other acoustic properties of the breast tissues from USCT measurement data. However, the high computational cost of FWI reconstruction represents a significant burden for its widespread application in a clinical setting. The research reported here investigates the use of a convolutional neural network (CNN) to learn a mapping from USCT waveform data to speed of sound estimates. The CNN was trained using a supervised approach with a task-informed loss function aiming at preserving features of the image that are relevant to the detection of lesions. A large set of anatomically and physiologically realistic numerical breast phantoms (NBPs) and corresponding simulated USCT measurements was employed during training. Once trained, the CNN can perform real-time FWI image reconstruction from USCT waveform data. The performance of the proposed method was assessed and compared against FWI using a hold-out sample of 41 NBPs and corresponding USCT data. Accuracy was measured using relative mean square error (RMSE), structural self-similarity index measure (SSIM), and lesion detection performance (DICE score). This numerical experiment demonstrates that a supervised learning model can achieve accuracy comparable to FWI in terms of RMSE and SSIM, and better performance in terms of task performance, while significantly reducing computational time.

Erratum: Long-Distance Coherent Propagation of High-Velocity Antiferromagnetic Spin Waves [Phys. Rev. Lett. 130, 096701 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.096701.

A wide megafauna gap undermines China's expanding coastal ecosystem conservation.

To fulfill sustainable development goals, many countries are expanding efforts to conserve ecologically and societally critical coastal ecosystems. Although megafauna profoundly affect the functioning of ecosystems, they are neglected as a key component in the conservation scheme for coastal ecosystems in many geographic contexts. We reveal a rich diversity of extant megafauna associated with all major types of coastal ecosystems in China, including 218 species of mammals, birds, reptiles, cephalopods, and fish across terrestrial and marine environments. However, 44% of these species are globally threatened, and 78% have not yet been assessed in China for extinction risk. More worrisome, 73% of these megafauna have not been designated as nationally protected species, and <10% of their most important habitats are protected. Filling this wide "megafauna gap" in China and globally would be a leading step as humanity strives to thrive with coastal ecosystems.

Scientific discovery in the age of artificial intelligence.

Artificial intelligence (AI) is being increasingly integrated into scientific discovery to augment and accelerate research, helping scientists to generate hypotheses, design experiments, collect and interpret large datasets, and gain insights that might not have been possible using traditional scientific methods alone. Here we examine breakthroughs over the past decade that include self-supervised learning, which allows models to be trained on vast amounts of unlabelled data, and geometric deep learning, which leverages knowledge about the structure of scientific data to enhance model accuracy and efficiency. Generative AI methods can create designs, such as small-molecule drugs and proteins, by analysing diverse data modalities, including images and sequences. We discuss how these methods can help scientists throughout the scientific process and the central issues that remain despite such advances. Both developers and users of AI toolsneed a better understanding of when such approaches need improvement, and challenges posed by poor data quality and stewardship remain. These issues cut across scientific disciplines and require developing foundational algorithmic approaches that can contribute to scientific understanding or acquire it autonomously, making them critical areas of focus for AI innovation.

Plant-inspired multifunctional fluorescent cellulose nanocrystals intelligent nanocomposite hydrogel.

Intelligent hydrogel has great application potentials in flexible sensing and artificial intelligence devices due to its intrinsic characteristics. However, developing an intelligent hydrogel with favorable properties including high strength, superior toughness, excellent conductivity and ionic sensing via a facile route is still a challenge. Herein, inspired by biologically chelating interactions of phytic acid (PA) in plants, a plant-inspired versatile intelligent nanocomposite hydrogel was readily fabricated by incorporating PA into the interface of fluorescent cellulose nanocrystals (F-CNC). Under PA "molecular bridge", the hydrogel simultaneously realized superflexibility (1000 %), high strength, superb self-healing ability, remarkable fluorescence and chloride ion sensibility as well as good ionic conductivity (2.4 S/m). The hydrogel could be assembled as a flexible sensor for real-time monitoring of human motion with excellent sensitivity and stability since high sensitivity toward both strain and pressure. F-CNC acted as a functional trigger could confer the hydrogel good fluorescence and high sensitivity toward chloride ion. This design confirms the synergy of F-CNC in boosting strength, ionic sensing, and ionic conductivity, addressing a long-standing dilemma among strength, stretchability, and sensitivity for intelligent hydrogel. The one-step incorporating tactic under mild ambient conditions may open an innovative avenue for the construction of intelligent hydrogel with novel properties.

The Sapria himalayana genome provides new insights into the lifestyle of endoparasitic plants.

BACKGROUND: Sapria himalayana (Rafflesiaceae) is an endoparasitic plant characterized by a greatly reduced vegetative body and giant flowers; however, the mechanisms underlying its special lifestyle and greatly altered plant form remain unknown. To illustrate the evolution and adaptation of S. himalayasna, we report its de novo assembled genome and key insights into the molecular basis of its floral development, flowering time, fatty acid biosynthesis, and defense responses. RESULTS: The genome of S. himalayana is ~ 1.92 Gb with 13,670 protein-coding genes, indicating remarkable gene loss (~ 54%), especially genes involved in photosynthesis, plant body, nutrients, and defense response. Genes specifying floral organ identity and controlling organ size were identified in S. himalayana and Rafflesia cantleyi, and showed analogous spatiotemporal expression patterns in both plant species. Although the plastid genome had been lost, plastids likely biosynthesize essential fatty acids and amino acids (aromatic amino acids and lysine). A set of credible and functional horizontal gene transfer (HGT) events (involving genes and mRNAs) were identified in the nuclear and mitochondrial genomes of S. himalayana, most of which were under purifying selection. Convergent HGTs in Cuscuta, Orobanchaceae, and S. himalayana were mainly expressed at the parasite-host interface. Together, these results suggest that HGTs act as a bridge between the parasite and host, assisting the parasite in acquiring nutrients from the host. CONCLUSIONS: Our results provide new insights into the flower development process and endoparasitic lifestyle of Rafflesiaceae plants. The amount of gene loss in S. himalayana is consistent with the degree of reduction in its body plan. HGT events are common among endoparasites and play an important role in their lifestyle adaptation.