Cancer is the leading cause of death worldwide, and its treatment and outcomes have been dramatically revolutionised by targeted therapies. As the most frequently mutated oncogene, Kirsten rat ...sarcoma viral oncogene homologue (KRAS) has attracted substantial attention. The understanding of KRAS is constantly being updated by numerous studies on KRAS in the initiation and progression of cancer diseases. However, KRAS has been deemed a challenging therapeutic target, even "undruggable", after drug-targeting efforts over the past four decades. Recently, there have been surprising advances in directly targeted drugs for KRAS, especially in KRAS (G12C) inhibitors, such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have obtained encouraging results in clinical trials. Excitingly, AMG510 was the first drug-targeting KRAS (G12C) to be approved for clinical use this year. This review summarises the most recent understanding of fundamental aspects of KRAS, the relationship between the KRAS mutations and tumour immune evasion, and new progress in targeting KRAS, particularly KRAS (G12C). Moreover, the possible mechanisms of resistance to KRAS (G12C) inhibitors and possible combination therapies are summarised, with a view to providing the best regimen for individualised treatment with KRAS (G12C) inhibitors and achieving truly precise treatment.
Non-line-of-sight (NLOS) imaging aims to reconstruct objects obscured by direct line of sight. Traditional Single-pixel Imaging (SPI) performs correlation operations on signals through the ...illumination pattern and intensity of a single-pixel detector. However, the reconstructed result mainly provides spatial information of objects, which limits its practical applications, including autonomous driving and smart cities for defense. In this work, leveraging active correlations-based imaging techniques, a multi-wavelength single-pixel non-line-of-sight (NLOS) reconstruction framework is proposed. By introducing compressive sensing, a Total Variation minimization (TV) RGB color space algorithm is designed for more object information reconstructions via under-sampling. The proposed approach is capable of reconstructing both the space and color information of hidden objects with fine detail under the intermediate reflector and filter settings. The experimental results demonstrate that the proposed scheme achieves a compression rate of 29% and outperforms conventional single-pixel imaging in terms of object information at low sampling rates, having potential practical applications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The contribution of factors including fuel type, fire-weather conditions, topography and human activity to fire regime attributes (e.g. fire occurrence, size distribution and severity) has been ...intensively discussed. The relative importance of those factors in explaining the burn probability (BP), which is critical in terms of fire risk management, has been insufficiently addressed. Focusing on a subtropical coniferous forest with strong human disturbance in East China, our main objective was to evaluate and compare the relative importance of fuel composition, topography, and human activity for fire occurrence, size and BP. Local BP distribution was derived with stochastic fire simulation approach using detailed historical fire data (1990-2010) and forest-resource survey results, based on which our factor contribution analysis was carried out. Our results indicated that fuel composition had the greatest relative importance in explaining fire occurrence and size, but human activity explained most of the variance in BP. This implies that the influence of human activity is amplified through the process of overlapping repeated ignition and spreading events. This result emphasizes the status of strong human disturbance in local fire processes. It further confirms the need for a holistic perspective on factor contribution to fire likelihood, rather than focusing on individual fire regime attributes, for the purpose of fire risk management.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Storm surge is one of the most devastating marine disasters in China, leading to tremendous economic damage and a large number of casualties. Combined storm surge hazard assessment and zonation is an ...important method for coastal disaster risk reduction and mitigation management. Based on observational data from tide-gauge and hydrological stations in coastal areas, we analyzed storm surge hazard intensity and generated a storm surge hazard map at the county level using the expected values of storm surge and over-warning water levels. The results show that 87, 67, 62, and 40 counties along the coast of China are exposed to the first (highest), second (higher), third (medium), and fourth (low) degree of hazard level, respectively. The areas with the highest risk of storm surge are the coasts of Bohai Bay, Laizhou Bay, and the Yangtze Delta, the coast from the north of Fuzhou to the south of Zhejiang, and the coastal area of Huizhou, Pearl River, and Yangjiang in Guangdong Province. This assessment, which is based on a national storm surge hazards map, can provide decision-making support for the government’s urban planning of coastal cities and site selection in large national projects.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Tumor immunotherapy, particularly the use of immune checkpoint inhibitors, has yielded impressive clinical benefits. Therefore, it is critical to accurately screen individuals for immunotherapy ...sensitivity and forecast its efficacy. With the application of artificial intelligence (AI) in the medical field in recent years, an increasing number of studies have indicated that the efficacy of immunotherapy can be better anticipated with the help of AI technology to reach precision medicine. This article focuses on the current prediction models based on information from histopathological slides, imaging-omics, genomics, and proteomics, and reviews their research progress and applications. Furthermore, we also discuss the existing challenges encountered by AI in the field of immunotherapy, as well as the future directions that need to be improved, to provide a point of reference for the early implementation of AI-assisted diagnosis and treatment systems in the future.
Background
Microvascular invasion (MVI) is a risk factor for tumor recurrence after hepatectomy in hepatocellular carcinoma (HCC) patients.
Objective
This study aimed to investigate the efficacy and ...safety of postoperative adjuvant transarterial infusion chemotherapy (TAI) with the FOLFOX regimen for HCC patients with MVI.
Methods
In this prospective, phase III, randomized, open-label, controlled clinical trial, HCC patients with histologically confirmed MVI were randomly assigned (1:1) after hepatectomy to receive either one to two cycles of adjuvant TAI (AT group) or follow-up without any adjuvant treatment (FU group). The primary endpoint was disease-free survival (DFS), while secondary endpoints were overall survival (OS) and safety.
Results
Between June 2016 and April 2019, 127 patients were randomly assigned to the AT group (
n
= 63) or FU group (
n
= 64). Clinicopathological characteristics of the two groups were well-balanced. The 6-, 12-, and 18-month OS rates for the AT group were 100.0%, 97.7%, and 97.7%, respectively, and 94.5%, 89.6%, and 78.5% for the FU group, respectively. The 6-, 12-, and 18-month DFS rates for the AT and FU groups were 84.7%, 61.8%, and 58.7%, and 62.9%, 48.1%, and 38.6%, respectively. OS and DFS were significantly better in the AT group than in the FU group (
p
= 0.037 and 0.023, respectively). No patients in the AT group experienced grade 3 or more severe adverse events.
Conclusions
Adjuvant TAI after hepatectomy may bring survival benefits to HCC patients with MVI.
Trial registration
Trial number: NCT03192618.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
► The functionally graded WC–Co/Ni component and 410 stainless steel were successfully brazed. ► The γ phase was suppressed in the joint due to isothermal solidification. ► (Cu,Ni)-based solid ...solution was formed between the braze and Ni layer. ► The functionally graded WC–Co/Ni component was beneficial to relaxing stresses.
The present investigation was conducted to research the brazing between a functionally graded WC–Co/Ni component and 410 stainless steel with Cu–Zn filler alloy. In the joint, γ phase was suppressed due to isothermal solidification and (Cu,Ni)-based solid solution was formed between the braze and Ni layer, which contributed to the intimate bonding of the WC–Co/Ni component and stainless steel. The functionally graded WC–Co/Ni component was beneficial to relaxing stresses and improving the strength of the cemented carbide/stainless steel joints.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Carbon nanotubes (CNTs) can improve the fracture toughness of ceramic composites. It is widely believed that defects in the CNTs will alter key properties that ultimately dictate composite ...toughening. However, to date there have been no studies that directly correlate these specific properties to controlled defect levels in CNTs. This type of investigation is presented here, using ceramic nanocomposites with a polymer derived ceramic (PDC) matrix, reinforced with multiwalled CNTs. This work includes basic fracture measurements on full composite films, combined with careful testing of individual CNTs embedded in the same PDC matrix. The defect levels in these CNTs were controlled with high energy carbon ions. By using this approach, it was possible to directly correlate defect levels with the interfacial shear strength (IFSS) of the CNT/PDC interface, the CNT fracture strengths, and the pull-out lengths observed after fracture of the full composites. The radiation induced defects led to substantial increases in the IFSS, and only a marginal decrease is observed in the measured fracture strength. Based on this, the shorter pull-out lengths that occurred with higher defect levels were primarily attributed to stronger bonding at the CNT/PDC interface.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
As an important food-borne human pathogen, Salmonella enterica serovar Typhimurium depends on its type III secretion system (T3SS) as a major virulence factor to cause disease all over the world. The ...T3SS secretes effector proteins to facilitate invasion into host cells. In this study, twenty prenylated flavonoids (1–20) were screened for their anti-T3SS activity, revealing that several analogs exhibited strong inhibitory effects on the secretion of Salmonella pathogenicity island 1 (SPI-1)-associated effector proteins without affecting the growth of bacteria and the secretion of the flagellar protein FliC. Among the flavonoids 1–20, licoflavonol (20) exhibited a strong inhibitory effect on the secretion of the SPI-1 effector proteins via regulating the transcription of the SicA/InvF genes, and the transportation of the effector protein SipC. In summary, licoflavonol, a novel natural inhibitor of Salmonella T3SS, could be a promising candidate for novel type of anti-virulence drugs.
•Licoflavonol (LCF) is an inhibitor of the Salmonella T3SS.•LCF inhibits the secretion of the Salmonella SPI-1-associated effector proteins.•LCF downregulates the transcription of the Salmonella SicA/InvF genes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study considered a probability-determinative method for evaluation of the probable maximum storm surge (PMSS) in the Wenchang area, Northeast Hainan Province, which focused on landfall location, ...selection of typhoon parameter combinations, and surge response exploration. Overall, 40 typhoon parameter combinations were derived based on analyses of historical records, including typhoon central pressure, approach speed, approach direction, radius of maximum wind speed (RMW), and ambient atmospheric pressure. We used the Finite-Volume Coastal Ocean Model driven by prototypical typhoon winds and atmospheric pressure fields to simulate astronomic tides and storm surges in sensitivity runs, for which typhoon cases were established for various landfall locations and typhoon parameter combinations. It was found that typhoons with intensity of 871 hPa and largest RMW of 60 km, moving at a fastest speed of 36 km/h with an approach direction of 285°, and making landfall similar to Typhoons Rammasun or Kalmaegi, could induce a PMSS along the northern region of Wenchang. Conversely, similar typhoons moving westward with an approach direction of 270°, and making landfall to the south of Wenchang, 60 km from the areas of interest, could induce PMSS along the middle and southern regions of Wenchang. The physical laws were verified based on comparison between the Rammasun and Kalmaegi storm surges. Total elevation and inundation simulations along coastal regions were performed through coupling of the PMSS and astronomic tides, where the astronomic tides were selected as the 90th percentile of the daily highest tide over 19 years. All conclusions stated in the paper were based on the characteristics of the coastlines and circumstances of the study region.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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