Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Pixelated non-volatile programmable photonic integrated circuits with 20-level intermediate states

Multi-level programmable photonic integrated circuits(PICs)and optical metasurfaces have gained widespread attention in many fields,such as neuromorphic photonics,opticalcommunications,and quantum information.In this paper,we propose pixelated programmable Si_(3)N_(4)PICs with record-high 20-level intermediate states at 785 nm wavelength.Such flexibility in phase or amplitude modulation is achieved by a programmable Sb_(2)S_(3)matrix,the footprint of whose elements can be as small as 1.2μm,limited only by the optical diffraction limit of anin-house developed pulsed laser writing system.We believe our work lays the foundation for laser-writing ultra-high-level(20 levels and even more)programmable photonic systems and metasurfaces based on phase change materials,which could catalyze diverse applications such as programmable neuromorphic photonics,biosensing,optical computing,photonic quantum computing,and reconfigurable metasurfaces.

Enhanced anomalous Hall effect in kagome magnet YbMn_(6)Sn_(6)with intermediate-valence ytterbium

We report on the magnetization and anomalous Hall effect(AHE)in the high-quality single crystals of the kagome magnet YbMn_(6)Sn_(6),where the spins of the Mn atoms in the kagome lattice order ferromagnetically and the intermediate-valence Yb atoms are nonmagnetic.The intrinsic mechanism plays a crucial role in the AHE,leading to an enhanced anomalous Hall conductivity(AHC)compared with the other rare-earth RMn_(6)Sn_(6)compounds.Our band structure calculation reveals a strong hybridization between the 4f electrons of Yb and conduction electrons.

Steam reforming of acetic acid over Ni/biochar of low metal-loading:Involvement of biochar in tailoring reaction intermediates renders superior catalytic performance

Biochar is a reactive carrier as it may be partially gasified with steam in steam reforming,which could influence the formation of reaction intermediates and modify catalytic behaviors.Herein,the Ni/biochar as well as two comparative catalysts,Ni/Al_(2)O_(3) and Ni/SiO_(2),with low nickel loading(2%(mass))was conducted to probe involvement of the varied carriers in the steam reforming.The results indicated that the Ni/biochar performed excellent catalytic activity than Ni/SiO_(2) and Ni/Al_(2)O_(3),as the biochar carrier facilitated quick conversion of the -OH from dissociation of steam to gasify the oxygen-rich carbonaceous intermediates like C=O and C-O-C,resulting in low coverage while high exposure of nickel species for maintaining the superior catalytic performance.In converse,strong adsorption of aliphatic intermediates over Ni/Al_(2)O_(3) and Ni/SiO_(2) induced serious coking with polymeric coke as the main type(21.5%and 32.1%,respectively),which was significantly higher than that over Ni/biochar(3.9%).The coke over Ni/biochar was mainly aromatic or catalytic type with nanotube morphology and high crystallinity.The high resistivity of Ni/biochar towards coking was due to the balance between formation of coke and gasification of coke and partially biochar with steam,which created developed mesopores in spent Ni/biochar while the coke blocked pores in Ni/Al_(2)O_(3) and Ni/SiO_(2) catalysts.

Strategic regulation of nitrogen-containing intermediates for enhanced nitrate reduction over Co_(3)O_(4)/SiC catalyst having multiple active centers

Regulating the intermediates involved in the electrocatalytic nitrate reduction reaction(NO_(3)RR)is crucial for the enhancement of reaction efficiency.However,it remains a great challenge to regulate the reaction intermediates through active site manipulation on the surface of the catalyst.Here,a family of n%-Co_(3)O_(4)/SiC(n=5,8,12,20)catalysts with a delicate percentage of Co^(2+)and Co^(3+)were prepared for NO_(3)RR.We found that Co^(3+)primarily acts as the active site for NO_(3)^(−)reduction to NO_(2)^(−),while Co^(2+)is responsible for the conversion of NO_(2)^(−)to NH_(3).Moreover,the conversion of these intermediates over the active sites is autonomous and separately controllable.Both processes synergistically accomplish the reduction of nitrate ions to synthesize ammonia.Combining the experimental studies and density functional theory(DFT)calculations,it is discovered the pathway(^(*)NHO→^(*)NHOH→^(*)NH_(2)OH→^(*)NH_(2)→^(*)NH_(3))is more favorable due to the lowerΔG value(0.25 eV)for the rate-limiting step(^(*)NO→^(*)NHO).The NH_(3)yield rate of 8%-Co_(3)O_(4)/SiC reached 1.08 mmol/(cm^(2)h)with a Faradaic efficiency of 96.4%at−0.89 V versus the reversible hydrogen electrode(RHE),surpassing those of most reported non-noble NO_(3)RR catalysts.This strategy not only provides an efficient catalyst for NO_(3)RR but also serves as an illustrative model for the regulation of multi-step reaction intermediates through the design of distinct active sites,thereby presenting a new approach to enhance the efficiency of intricate reactions.

Regulating^(*)COOH intermediate via amino alkylation engineering for exceptionally effective photocatalytic CO_(2) reduction

Photocatalytic reduction of CO_(2) into fuel represents a promising approach for achieving carbon neutrality,while realizing high selectivity in this process is challenging due to uncontrollable reaction intermediate and retarded desorption of target products.Engineering the interface microenvironment of catalysts has been proposed as a strategy to exert a significant influence on reaction outcomes,yet it remains a significant challenge.In this study,amino alkylation was successfully integrated into the melem unit of polymeric carbon nitrides(PCN),which could efficiently drive the photocatalytic CO_(2) reduction.Experimental characterization and theoretical calculations revealed that the introduction of amino alkylation lowers the energy barrier for CO_(2) reduction into^(*)COOH intermediate,transforming the adsorption of^(*)COOH intermediate from the endothermic to an exothermic process.Notably,the as-prepared materials demonstrated outstanding performance in photocatalytic CO_(2) reduction,yielding CO_(2)at a rate of 152.8μmol h^(-1) with a high selectivity of 95.4%and a quantum efficiency of 6.6%.

The study of intelligent algorithm in particle identification of heavy-ion collisions at low and intermediate energies

Traditional particle identification methods face timeconsuming,experience-dependent,and poor repeatability challenges in heavy-ion collisions at low and intermediate energies.Researchers urgently need solutions to the dilemma of traditional particle identification methods.This study explores the possibility of applying intelligent learning algorithms to the particle identification of heavy-ion collisions at low and intermediate energies.Multiple intelligent algorithms,including XgBoost and TabNet,were selected to test datasets from the neutron ion multi-detector for reaction-oriented dynamics(NIMROD-ISiS)and Geant4 simulation.Tree-based machine learning algorithms and deep learning algorithms e.g.TabNet show excellent performance and generalization ability.Adding additional data features besides energy deposition can improve the algorithm’s performance when the data distribution is nonuniform.Intelligent learning algorithms can be applied to solve the particle identification problem in heavy-ion collisions at low and intermediate energies.

Freshening of the Intermediate Waters in the Northern South China Sea over the Past Six Decades

The properties of salinity in the South China Sea(SCS),a significant marginal sea connecting the Pacific and Indian Oceans,are greatly influenced by the transport of fresh water flux between the two oceans.However,the long-term changes in the intermediate water in the SCS have not been thoroughly studied due to limited data,particularly in relation to its thermodynamic variations.This study utilized reanalysis data products to identify a 60-year trend of freshening in the intermediate waters of the northern South China Sea(NSCS),accompanied by an expansion of low-salinity water.The study also constructed salinity budget terms,including advection and entrainment processes,and conducted an analysis of the salinity budget to understand the impacts of external and internal dynamic processes on the freshening trend of the intermediate water in the NSCS.The analysis revealed that the freshening in the northwest Pacific Ocean and the intensification of intrusion through the Luzon Strait at intermediate levels are the primary drivers of the salinity changes in the NSCS.Additionally,a weakened trend in the intensity of vertical entrainment also contributes to the freshening in the NSCS.This study offers new insights into the understanding of regional deep sea changes in response to variations in both thermodynamics and oceanic dynamic processes.

Analyzing the Essay Writing Patterns of Iranian Intermediate-Level Korean Language Learners: A Study Based on the TOPIK Exam

This study examines the writing abilities of Iranian intermediate Korean learners,specifically their performance in the compositional writing section of the Test of Proficiency in Korean(TOPIK).By utilizing the many FACETS-Rasch Model,we meticulously analyzed nine writing samples from the 52nd TOPIK.These samples were evaluated using a modified rubric ranging from 0 to 3 based on predefined criteria for written composition.The results underscored that the sections on“appropriateness of spacing and spelling,”“relevance of vocabulary,”and“content diversity”presented the most significant challenges for the learners.On the other hand,“the quantity of writing”emerged as the least challenging aspect.These findings reveal substantial disparities in various aspects of writing proficiency among learners.The study not only pinpoints issue areas in writing skills,but also underscores the necessity of customized teaching strategies within the TOPIK framework to address these weaknesses.Consequently,it offers valuable insights that could bolster the effectiveness of teaching writing to Korean language learners.The findings of this study are not only significant for the field of language education,but also contribute to a deeper understanding of the challenges faced by intermediate learners and provide a roadmap for improving language instruction.

Changes in the Supply of Public Intermediate Goods,Fixed Wage,and the Relative Price in the Harris-Todaro Model

Since the Harris-Todaro model was proposed in 1970,it has played a crucial role in analyzing various environmental and trade issues in developing countries.This paper analyzes the effects of the amount of public intermediate goods provided by the government,the increase in the fixed wage rate in the urban sector,and the changes in the relative international prices of agricultural and manufacturing goods on labor employment,unemployment,and the economic welfare in the context of a small open economy.It also proposes relevant policies to reduce the unemployment rate while improving national welfare.

An Intermediate Reference Datum Static Correction Technique and Its Applications

Static corrections using the conventional method are basically conducted in two steps, the weathering correction followed by the correction from the top of the sub-weathering to the unified datum. However, the conventional method fails to well deal with statics problems in case the top of the sub-weathering is sharply undulated and the lateral velocity of the sub-weathering varies significantly. This brings us to the introduction of a smooth intermediate reference datum （IRD） located under the top of the sub-weathering, which helps to further increase the accuracy of statics based on the weathering corrections, and ensures the imaging quality. Good results based on the IRD technique have been achieved in the complex areas in western China. This paper discusses the IRD functions, its application requirements, and selection of related parameters. Some typical sections for comparison are also given in this paper.

Selective reduction of carbon dioxide to carbon monoxide over Au/CeO_2 catalyst and identification of reaction intermediate

CO2 selective reduction to CO with H2 over a CeO2-supported nano-Au catalyst at atmospheric pres- sure was investigated. A high CO2 conversion, approaching the thermodynamic equilibrium value, and nearly 100% CO selectivity were obtained. The surface formate intermediates generated during the reverse water-gas shift reaction at 400 ℃ were identified using in situ diffuse-reflectance infra- red Fourier-transform spectroscopy. The formate consumption to give CO and H20, determined using mass spectrometry, indicated that the reaction proceeded via an associative formate mecha- nism; this contributes to the high Au/CeO2 catalytic activity at low temperatures.

Transformations and Tautomeric Equilibrium among Different Intermediates in Proline-Catalyzed Reactions of Aldehydes or Ketones

The enamines, iminium ions, and oxazolidinones are thought to be the key intermediates in the proline-catalyzed reactions of aldehydes or ketones, but there is an extensive contro- versy about their roles. Here, the corresponding transition states connecting any two of the three kinds of species are located at the wB97XD/6-311＋＋G＊＊ level of theory. The calcula- tions demonstrate that the oxazolidinones are the predominant species in both the gas phase and solvents; there exists tautomeric equilibrium among these species and the equilibriums are controlled by the employed solvents and temperature in the reaction. These results demonstrate that the concentration and role of the mentioned species are controlled by the employed solvent and temperature. A new reaction pathway is presented herein for the trans- formation between iminium ions and oxazolidinones through iminium ion-water complex and oxazolidinone-water complex. The calculations demonstrate that the rate-limiting step in proline-catalyzed Mannich reaction between acetaldehyde/keteones and N-Boc imines is the formation of the C-C bond rather than the intermediates tautomerization. These calculations rationalize the available experimental observations and can be valuable in optimizing the experimental conditions of asymmetric organic-catalyzed reactions of aldehydes or ketones.

Improved ENSO Forecasts by Assimilating Sea Surface Temperature Observations into an Intermediate Coupled Model

A simple method for initializing intermediate coupled models （ICMs） using only sea surface temperature （SST） anomaly data is comprehensively tested in two sets of hindcasts with a new ICM. In the initialization scheme, both the magnitude of the nudging parameter and the duration of the assimilation are considered, and initial conditions for both atmosphere and ocean are generated by running the coupled model with SST anomalies nudged to the observations. A comparison with the observations indicates that the scheme can generate realistic thermal fields and surface dynamic fields in the equatorial Pacific through hindcast experiments. An ideal experiment is performed to get the optimal nudging parameters which include the nudging intensity and nudging time length. Twelve-month-long hindcast experiments are performed with the model over the period 1984-2003 and the period 1997-2003. Compared with the original prediction results, the model prediction skills are significantly improved by the nudging method especially beyond a 6-month lead time during the two different periods. Potential problems and further improvements are discussed regarding the new coupled assimilation system.

Chlorobenzene degradation by electro-heterogeneous catalysis in aqueous solution:intermediates and reaction mechanism

This study was performed to investigate the variables that influence chlorobenzene (CB) degradation in aqueous solution by electro-heterogeneous catalysis.The effects of current density,pH,and electrolyte concentration on CB degradation were determined.The degradation effciency of CB was almost 100% with an initial CB concentration of 50 mg/L,current density 15 mA/cm2,initial pH 10,electrolyte concentration 0.1 mol/L,and temperature 25°C after 90 min of reaction.Under the same conditions,the degradation eff...

Mechanism study on UV-induced photodegradation of nonylphenol ethoxylates by intermediate products analysis

Photodegradation of nonylphenol ethoxylates （NPloEO） was investigated in laboratory scale under UV irradiation. The intermediate photodegradation products were analyzed by LC-ESI-MS. Three kinds of intermediate products including aldehydic compounds, carboxylic compounds and cyclohexanyl compounds were identified. Five main degradation routes involving the oxidation of the alkyl chain and ethoxylate unit, shortening of the alkyl chain and ethoxylate unit, hydrogenation of the benzene ring were proposed.

Testing a Four-Dimensional Variational Data Assimilation Method Using an Improved Intermediate Coupled Model for ENSO Analysis and Prediction

A four-dimensional variational （4D-Var） data assimilation method is implemented in an improved intermediate coupled model （ICM） of the tropical Pacific. A twin experiment is designed to evaluate the impact of the 4D-Var data assimilation algorithm on ENSO analysis and prediction based on the ICM. The model error is assumed to arise only from the parameter uncertainty. The ＂observation＂ of the SST anomaly, which is sampled from a ＂truth＂ model simulation that takes default parameter values and has Gaussian noise added, is directly assimilated into the assimilation model with its parameters set erroneously. Results show that 4D-Var effectively reduces the error of ENSO analysis and therefore improves the prediction skill of ENSO events compared with the non-assimilation case. These results provide a promising way for the ICM to achieve better real-time ENSO prediction.

Intermediate-depth earthquakes beneath the Pamir-Hindu Kush Region:Evidence for collision between two opposite subduction zones

We employed a double-difference algorithm （hypoDD） to relocate earthquakes within the region bounded by 66°E-78°E and 32°N-42°N in the period of 1964-2003 reported by the International Seismological Center （ISC）. The improved hypocentral locations delineate a double-layered Wadati-Benioff zone in the eastern Hindu Kush intermediate seismic belt. Based on this feature and other evidences, we propose that the intermediate-depth earthquakes beneath the Pamir-Hindu Kush region may occur in two collided subduction zones with opposite dip directions.

Origins and pathways of the subsurface and intermediate water masses of the Indonesian Throughflow derived from historical and Argo data

On the basis of Argo data and historic temperature/salinity data from the World Ocean Database 2001 （ WOD01 ）, origins and spreading pathways of the subsurface and intermediate water masses in the Indonesian Throughflow （ITF） region were discussed by analyzing distributions of salinity on representative isopyenal layers. Results were shown that, subsurface water mostly comes from the North Pacific Ocean while the intermediate water originates from both the North and South Pacific Ocean, even possibly from the Indian Ocean. Spreading through the Sulawesi Sea, the Makassar Strait, and file Flores Sea, the North Pacific subsurface water and the North Pacific Intermediate water dominate the western part of the Indonesian Archipelago. Furthermore as the depth increases, the features of the North Pacific sourced water masses become more obvious. In the eastern part of the waters, high sa- linity South Pacific subsurface water is blocked by a strong salinity front between Halmahera and New Guinea. Intermediate water in the eastern interior region owns salinity higher than the North Pacific intermediate water and the antarctic intermediate water （ AAIW）, possibly coming from the vertical mixing between subsurface water and the AAIW from the Pacific Ocean, and possibly coming from the northward extending of the AAIW from the Indian Ocean as well.

Steam reforming of acetic acid over Ni-Ba/Al2O3 catalysts:Impacts of barium addition on coking behaviors and formation of reaction intermediates

The influence of barium addition to a Ni/Al2O3 catalyst on the reaction intermediates formed,the activity,resistance of the catalyst to coking,and properties of the coke formed after acetic acid steam reforming were investigated in this study.The results showed the drastic effects of barium addition on the physicochemical properties and performances of the catalyst.The solid-phase reaction between alumina and BaO formed BaAl2O4,which re-constructed the alumina structure,resulting in a decrease in the specific surface area and an increase in the resistance of metallic Ni to sintering.The addition of barium was also beneficial for enhancing the catalytic activity,resulting from the changed catalytic reaction network.The in-situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) study of the acetic acid steam reforming indicated that barium could effectively suppress the accumulation of the reaction intermediates of carbonyl,formate,and C=C functional groups on the catalyst surface,attributed to its relatively high ability to cause the gasification of these species.In addition,coking was considerably more significant over the Ba-Ni/Al2O3 catalyst.Moreover,the Ba-Ni/Al2O3 catalyst was more stable than the Ni/Al2O3catalyst,owing to the distinct forms of coke formed (carbon nanotube form over the Ba-Ni/Al2O3 catalyst,and the amorphous form over the Ni/Al2O3 catalyst).