Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

Probing the Surface Layer Modulation on Archaeal Mechanics and Adhesion at the Single-Cell Level.

Addressing the challenge of understanding how cellular interfaces dictate the mechanical resilience and adhesion of archaeal cells, this study demonstrates the role of the surface layer (S-layer) in methanogenic archaea. Using a combination of atomic force microscopy and single-cell force spectroscopy, we quantified the impact of S-layer disruption on cell morphology, mechanical properties, and adhesion capabilities. We demonstrate that the S-layer is crucial for maintaining cell morphology, where its removal induces significant cellular enlargement and deformation. Mechanical stability of the cell surface is substantially compromised upon S-layer disruption, as evidenced by decreased Young's modulus values. Adhesion experiments revealed that the S-layer primarily facilitates hydrophobic interactions, which are significantly reduced after its removal, affecting both cell-cell and cell-bubble interactions. Our findings illuminate the S-layer's fundamental role in methanogen architecture and provide a chemical understanding of archaeal cell surfaces, with implications for enhancing methane production in biotechnological applications.

Simultaneous Reconstruction of Multiple Time-Varying Thermal Properties Based on Translucent Materials.

In the realm of high-tech materials and energy applications, accurately measuring the transient heat flow at media boundaries and the internal thermal conductivity of materials in harsh heat exchange environments poses a significant challenge when using conventional direct measurement methods. Consequently, the study of photothermal parameter reconstruction in translucent media, which relies on indirect measurement techniques, has crucial practical value. Current research on reconstructing photothermal properties within participating media typically focuses on single-objective or time-invariant properties. There is a pressing need to develop effective methods for the simultaneous reconstruction of time-varying thermal flow fields and internal thermal conductivity at the boundaries of participating media. This paper introduces a computational model based on the numerical simulation theory of internal heat transfer systems in participating media, stochastic particle swarm optimization algorithms, and Kalman filter technology. The model aims to enable the simultaneous reconstruction of various thermal parameters within the target medium. Our results demonstrate that under varying levels of measurement noise, the inversion results for different target parameters exhibit slight oscillations around the true values, leading to a reduction in reconstruction accuracy. However, overall, the model demonstrates robustness and accuracy in ideal conditions, validating its effectiveness.

Nitrogen Forms Regulate the Response of Microcystis aeruginosa to Nanoplastics at Environmentally Relevant Nitrogen Concentrations.

As essential primary producers, cyanobacteria play a major role in global carbon and nitrogen cycles. Though the influence of nanoplastics on the carbon metabolism of cyanobacteria is well-studied, little is known about how nanoplastics affect their nitrogen metabolism, especially under environmentally relevant nitrogen concentrations. Here, we show that nitrogen forms regulated growth inhibition, nitrogen consumption, and the synthesis and release of microcystin (MC) in Microcystis aeruginosa exposed to 10 µg/mL amino-modified polystyrene nanoplastics (PS-NH2) with a particle size of 50 nm under environmentally relevant nitrogen concentrations of nitrate, ammonium, and urea. We demonstrate that PS-NH2 inhibit M. aeruginosa differently in nitrate, urea, and ammonium, with inhibition rates of 51.87, 39.70, and 36.69%, respectively. It is caused through the differences in impairing cell membrane integrity, disrupting redox homeostasis, and varying nitrogen transport pathways under different nitrogen forms. M. aeruginosa respond to exposure of PS-NH2 by utilizing additional nitrogen to boost the production of amino acids, thereby enhancing the synthesis of MC, extracellular polymeric substances, and membrane phospholipids. Our results found that the threat of nanoplastics on primary producers can be regulated by the nitrogen forms in freshwater ecosystems, contributing to a better understanding of nanoplastic risks under environmentally relevant conditions.

Hygrothermal Effect on GF/VE and GF/UP Composites: Durability Performance and Laboratory Assessment.

In order to investigate the durability of two kinds of fiber-reinforced composite materials, and obtain the degradation mechanism and failure model in a hygrothermal environment, E-glass- fiber-reinforced composite materials, glass fiber-reinforced epoxy vinyl ester and glass fiber-reinforced unsaturated polyester (named GF/VE and GF/UP, respectively) were chosen to suffer rigorous hygrothermal aging. Their mechanical performance was monitored during the aging process to evaluate their durability. The cause of deterioration of the composite was comprehensively analyzed. Based on the analysis results of attenuated total-reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA), the change mechanism of chain structure of the resin molecule was proposed. SEM (scanning electron microscopy), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) were used to analyze the microstructure and degradation mechanism of the fiber and the interface between fiber and matrix. The degradation mechanism of the composite system, including the resin, the fiber and the interface, was obtained, and it was found that the deterioration of the matrix resin caused by the hygrothermal environment was the main factor leading to the decline in composites performance.

Characterization of AST-001 non-clinical pharmacokinetics: A novel selective AKR1C3-activated prodrug in mice, rats, and cynomolgus monkeys.

AST-001 is a chemically synthesized inactive nitrogen mustard prodrug that is selectively cleaved to a cytotoxic aziridine (AST-2660) via aldo-keto reductase family 1 member C3 (AKR1C3). The purpose of this study was to investigate the pharmacokinetics and tissue distribution of the prodrug, AST-001, and its active metabolite, AST-2660, in mice, rats, and monkeys. After single and once daily intravenous bolus doses of 1.5, 4.5, and 13.5 mg/kg AST-001 to Sprague-Dawley rats and once daily 1 h intravenous infusions of 0.5, 1.5, and 4.5 mg/kg AST-001 to cynomolgus monkeys, AST-001 exhibited dose-dependent pharmacokinetics and reached peak plasma levels at the end of the infusion. No significant accumulation and gender differences were observed after 7 days of repeated dosing. In rats, the half-life of AST-001 was dose independent and ranged from 4.89 to 5.75 h. In cynomolgus monkeys, the half-life of AST-001 was from 1.66 to 5.56 h and increased with dose. In tissue distribution studies conducted in Sprague-Dawley rats and in liver cancer PDX models in female athymic nude mice implanted with LI6643 or LI6280 HepG2-GFP tumor fragments, AST-001 was extensively distributed to selected tissues. Following a single intravenous dose, AST-001 was not excreted primarily as the prodrug, AST-001 or the metabolite AST-2660 in the urine, feces, and bile. A comprehensive analysis of the preclinical data and inter-species allometric scaling were used to estimate the pharmacokinetic parameters of AST-001 in humans and led to the recommendation of a starting dose of 5 mg/m2 in the first-in-human dose escalation study.

SENP1 attenuates hypoxia­reoxygenation injury in liver sinusoid endothelial cells by relying on the HIF­1α signaling pathway.

Liver sinusoidal endothelial cells (LSECs) have an important role in hepatic ischemia­reperfusion injury (I/R), but the specific molecular mechanism of action is unknown. LSEC proliferation is regulated and fenestration is maintained via the Sentrin/SUMO­specific protease 1 (SENP1)/hypoxia­inducible factor­1α (HIF­1α) signaling axis under hypoxic conditions. In the present study, a hypoxia­reoxygenation (H­R) injury model was established using mouse LSECs to explore the relationship between SENP1 and H­R injury in vitro, and the specific underlying mechanism was identified, revealing new targets for the clinical attenuation of hepatic I/R injury. Following the culture of LSECs under H­R conditions, it was demonstrated that the expression of SENP1 was upregulated by reverse transcription­quantitative polymerase chain reaction and western blotting (WB). In addition, scanning electron microscopy indicated that fenestrae damage was increased, a Cell Counting Kit­8 assay demonstrated that the proliferation of cells was impaired and flow cytometry showed that apoptosis was increased. After silencing SENP1 expression with short interfering RNA, the proliferation activity of LSECs decreased, the fenestrae damage increased, the apoptosis rate increased and the expression levels of SENP1, HIF­1α, heme oxygenase and Bcl­2 were downregulated (as demonstrated by WB), while the expression levels of apoptosis­related proteins, cleaved­caspase­3 and Bax, were upregulated. Enzyme­linked immunosorbent assay detection showed that the level of vascular endothelial growth factor in the supernatant decreased and the level of IL­6 and TNF­α increased. Following the administration of an HIF­1α signaling pathway agonist, the situation was reversed. These results therefore suggested that SENP1 attenuated the reduction in proliferation, apoptosis and fenestration of LSECs observed following H­R injury through the HIF­1α signaling pathway. In conclusion, SENP1 may attenuate H­R injury in LSECs in a HIF­1α signaling pathway­dependent manner.

Assessing the spatial occupation and ecological impact of human activities in Chengguan district, Lhasa city, Tibetan Plateau.

In this study, the ecological impact of human activities and the space occupied by construction and arable land on the Tibetan Plateau were examined, focusing on changes in the net primary productivity (NPP) as a key indicator of ecological health. With the utilization of land use data and multiyear average NPP data from 2002 to 2020, we analyzed the effects of the conversion of zonal vegetation into construction and arable land on carbon sequestration and oxygen release in Chengguan District, Lhasa city. Our findings indicated a marked spatial difference in the NPP among different land types. Regarding the original zonal vegetation, the NPP ranged from 0.2 to 0.3 kg/m2. Construction land showed a decrease in the NPP, with values ranging from 0.16 to 0.26 kg/m2, suggesting a decrease in ecological productivity. Conversely, arable land exhibited an increase in the NPP, with average values exceeding 0.3 kg/m2. This increase suggested enhanced productivity, particularly in regions where the original zonal vegetation provided lower NPP values. However, this enhanced productivity may not necessarily indicate a positive ecological change. In fact, such increases could potentially disrupt the natural balance of ecosystems, leading to unforeseen ecological consequences. The original zonal vegetation, with NPP values ranging from 0.12 to 0.43 kg/m2, exhibited higher ecological stability and adaptability than the other land types. This wider NPP range emphasizes the inherent resilience of native vegetation, which could sustain diverse ecological functions under varying environmental conditions. These findings demonstrate the urgent need for sustainable land use management on the Tibetan Plateau. This study highlights the importance of considering the ecological impact of land use changes in regional development strategies, ensuring the preservation and enhancement in the unique and fragile plateau ecosystem.

A hybrid photocatalytic system enables direct glucose utilization for methanogenesis.

Integration of methanogenic archaea with photocatalysts presents a sustainable solution for solar-driven methanogenesis. However, maximizing CH4 conversion efficiency remains challenging due to the intrinsic energy conservation and strictly restricted substrates of methanogenic archaea. Here, we report a solar-driven biotic-abiotic hybrid (biohybrid) system by incorporating cadmium sulfide (CdS) nanoparticles with a rationally designed methanogenic archaeon Methanosarcina acetivorans C2A, in which the glucose synergist protein and glucose kinase, an energy-efficient route for glucose transport and phosphorylation from Zymomonas mobilis, were implemented to facilitate nonnative substrate glucose for methanogenesis. We demonstrate that the photo-excited electrons facilitate membrane-bound electron transport chain, thereby augmenting the Na+ and H+ ion gradients across membrane to enhance adenosine triphosphate (ATP) synthesis. Additionally, this biohybrid system promotes the metabolism of pyruvate to acetyl coenzyme A (AcCoA) and inhibits the flow of AcCoA to the tricarboxylic acid (TCA) cycle, resulting in a 1.26-fold augmentation in CH4 production from glucose-derived carbon. Our results provide a unique strategy for enhancing methanogenesis through rational biohybrid design and reprogramming, which gives a promising avenue for sustainably manufacturing value-added chemicals.

Hierarchical attention-guided multiscale aggregation network for infrared small target detection.

All man-made flying objects in the sky, ships in the ocean can be regarded as small infrared targets, and the method of tracking them has been received widespread attention in recent years. In search of a further efficient method for infrared small target recognition, we propose a hierarchical attention-guided multiscale aggregation network (HAMANet) in this thesis. The proposed HAMANet mainly consists of a compound guide multilayer perceptron (CG-MLP) block embedded in the backbone net, a spatial-interactive attention module (SiAM), a pixel-interactive attention module (PiAM) and a contextual fusion module (CFM). The CG-MLP marked the width-axis, height-axis, and channel-axis, which can result in a better segmentation effect while reducing computational complexity. SiAM improves global semantic information exchange by increasing the connections between different channels, while PiAM changes the extraction of local key information features by enhancing information exchange at the pixel level. CFM fuses low-level positional information and high-level channel information of the target through coding to improve network stability and target feature utilization. Compared with other state-of-the-art methods on public infrared small target datasets, the results show that our proposed HAMANet has high detection accuracy and a low false-alarm rate.

Combined role of ground cover management in altering orchard surface‒subsurface erosion and associated carbon-nitrogen-phosphorus loss.

The combined role of ground cover management in controlling soil erosion and nutrient loss from new orchards is still less understood. In this study, four ground cover management practices, orchard with grass cover (OG), orchard with interplant cover (OI), orchard with straw cover (OS), and orchard with bare ground (OB), were designed to identify their impacts on soil erosion and associated carbon-nitrogen-phosphorus loss in new orchards by rainfall simulation tests with rainfall intensities of 60, 90, and 120 mm h-1 and 90 min rainfall duration. The results showed that OS had the lowest surface flow coefficient (6.6%) and highest subsurface flow coefficient (32.5%). The highest soil loss rate occurred in the OB plot (65.4 g m-2 min-1), and the lowest soil loss rate occurred in the OS plot (0.5 g m-2 min-1). OS plot showed better effectiveness in improving soil erosion. However, the increased infiltration capacity was facilitated in terms of causing non-point source pollution. The C-N-P ratios of surface flow in different cover measures (OB, OI, OG, and OS) were 1.4:1.2:0.9:1, 1.8:1.7:1.2:1, and 2.3:1.9:1.2:1, respectively. The ratios of sediment in different cover measures were 7.3:9:2.3:1, 2:1.5:1.2:1, and 1.2:1:0.8:0.7, respectively. Cover management plots play an active role in reducing nutrient loss in surface flow and sediment, but the increased infiltration in covered management plots is associated with the risk of groundwater contamination in subsurface flow. The C-N-P ratios of subsurface flow in OB and covered managed plots (OI, OG, and OS) were 1:3.3:1.6:2.7, 1:1.5:2.2:2.4 and 1:1.2:1.5:1.3, respectively. Therefore, when managing the phenomenon of soil erosion through ground cover measures, attention should also be focused on the function of cover measures in regulating non-point source pollution underground, such as subsurface flow. This research recommends a combination of cover management measures to further mitigate erosion and the risk of groundwater contamination.

Assessment of no-observed-effect-levels for DNA adducts formation by genotoxic carcinogens in fetal turkey livers.

For genotoxic carcinogens, covalent binding to DNA is a critical initiating event in tumorigenesis. The present research investigated dose-effect relationships of three genotoxic carcinogens representing different structural classes, 2-acetylaminofluorene (2-AAF), benzo[a]pyrene (B[a]P) and quinoline (QUI), to assess the existence of no-observed-effect-levels (NOELs) for the formation of DNA adducts. Carcinogens were administered into the air sac of fertilized turkey eggs over wide dose ranges in three daily injections on days 22 to 24 of incubation. DNA adducts were measured in the fetal turkey livers by the 32P-nucleotide postlabeling (NPL) assay. B[a]P and QUI produced DNA adducts in a dosage-related manner and exhibited NOELs at 0.65 and 0.35 mg/kg bw/day, respectively. In contrast, 2-AAF formed DNA adducts at all tested dosages down to 0.005 mg/kg bw/day. Benchmark dose (BMD) analysis identified the potencies of 2-AAF and QUI to be similar, while B[a]P was the least potent compound. Overall, findings in fetal turkey livers demonstrated that exposure levels to genotoxic compounds that do not result in DNA adducts can exist but are not evident with all carcinogens of this type. The use of mechanistic dose-effect studies for genotoxic endpoints can provide critical information for prioritization of concerns for risk assessment.

Exploration for Asian longhorned beetle parasitoids in Korea using an improved sentinel log trap.

The Asian longhorned beetle (ALB), Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae), is a destructive invasive woodboring insect pest, and efforts are being made to find parasitoids for ALB biological control. Through a four-year survey in Korea using a sentinel log trap associated with host chemical cues potentially important for host finding by parasitoids, two parasitoid species were discovered attacking ALB. One species is Spathius ibarakius Belokobylskij & Maetô, which is known to also parasitize citrus longhorned beetle, Anoplophora chinensis (Forster). The other parasitoid species, whose offspring were dead before imago, could not be morphologically identified at the adult stage. We attempted molecular and morphological identification of the larvae/pupae of the unidentified parasitoid; however, only superfamily-level identification was possible. The parasitism rate recovered in the logs was 0.3% by the unidentified parasitoid in Gapyeong-gun in 2019, while it reached 29.2% by S. ibarakius in Busan city in 2022. Future efforts for exploring ALB natural enemies in the pest's native range may focus on parasitoids with high parasitism rates.

Title: Exploration des parasitoïdes du longicorne asiatique en Corée à l'aide d'un piège à bûche sentinelle amélioré. Abstract: Le longicorne asiatique (LA), Anoplophora glabripennis (Motschulsky) (Coleoptera : Cerambycidae), est un insecte ravageur envahissant et destructeur du bois, et des efforts sont déployés pour trouver des parasitoïdes pour la lutte biologique contre lui. Au cours d'une étude de quatre ans en Corée utilisant un piège à bûche sentinelle associé à des signaux chimiques de l'hôte potentiellement importants pour la détection de l'hôte par les parasitoïdes, deux espèces de parasitoïdes ont été découvertes attaquant le longicorne. Une espèce est Spathius ibarakius Belokobylskij & Maetô, qui est connue pour parasiter également le longicorne des agrumes, Anoplophora chinensis (Forster). Les autres espèces de parasitoïdes, dont les descendants sont morts avant l'imago, n'ont pu être identifiées morphologiquement au stade adulte. Nous avons tenté une identification moléculaire et morphologique des larves/pupes du parasitoïde non identifié, mais seule une identification au niveau de la superfamille a été possible. Le taux de parasitisme observé dans les bûches était de 0,3 % par le parasitoïde non identifié à Gapyeong-gun en 2019, tandis qu'il atteignait 29,2 % par S. ibarakius dans la ville de Busan en 2022. Les efforts futurs pour explorer les ennemis naturels du capricorne dans l'aire de répartition naturelle du ravageur pourraient se concentrer sur les parasitoïdes à taux de parasitisme élevés.

Laser-Textured Hybrid Brass Pattern Array Surface for High-Efficiency Fog Collection.

Fog collection holds promise for addressing water shortage. However, the conventional fabrication of fog collection devices, normally chemical methods, suffers many challenges, such as complicated preparation and environmental issues. Herein, we proposed a green fabrication strategy to construct superhydrophobic/hydrophilic surfaces on the brass substrate via the combination of laser fabrication and heat treatment. The wettability of brass is directly dictated by the laser process parameters. The different superhydrophobic/hydrophilic hybrid pattern surface with a rectangular/triangular array was designed for an optimal fog collection performance. The maximum water collection efficiency of the prepared surface is measured up to 427.36 mg h-1 cm-2, which is 97% higher than that of the control sample. Furthermore, the surface can be folded into different forms to realize a flexible collector. We envision that our work provides a green fabrication strategy to construct a superwetting surface for highly efficient fog collection.

Parasitoid-induced changes in metabolic rate and feeding activity of the emerald ash borer (Coleoptera: Buprestidae): implications for biological control.

Parasitoid-host interactions form the foundation of biological control strategies against many agriculture and forest insect pests. The emerald ash borer (EAB), Agrilus planipennis (Coleoptera: Buprestidae), is a serious invasive pest of ash (Fraxinus spp.) trees in North America. Tetrastichus planipennisi (Hymenoptera: Eulophidae) is a gregarious, koinobiont endoparasitoid, attacking late (3rd to 4th) instars of EAB larvae, which feed in the live phloem of ash trunks or branches, making serpentine-like galleries filled with larval frass. In the present study, we tested the hypothesis that T. planipennisi regulates the host metabolism and feeding activity to optimize its offspring development and fitness. We first compared the respiration rate of parasitized and unparasitized host larvae at different times after parasitism, and then measured feeding activity of both parasitized and unparasitized host larvae inside their feeding galleries. Although parasitized host larvae increased metabolic rate and feeding activity in the first few days of parasitism, T. planipennisi parasitism induced an overall reduction of the metabolic rate and decrease in feeding activity of parasitized host larvae over their development period. In addition, there was a negative relationship between feeding activity of parasitized hosts and brood sizes of the parasitoid progeny-i.e., the more parasitoid progeny a host larva received, the less feeding activity the host had. These findings suggest that T. planipennisi has limited ability to optimize its offspring development and fitness through regulations of the host metabolism and feeding activity and its parasitism reduces feeding damage of parasitized EAB larvae to infested ash trees.

Incorporation of Selenium Derived from Nanoparticles into Plant Proteins in Vivo.

Diets comprising selenium-deficient crops have been linked to immune disorders and cardiomyopathy. Selenium nanoparticles (SeNPs) have emerged as a promising nanoplatform for selenium-biofortified agriculture. However, SeNPs fail to reach field-scale applications due to a poor understanding of the fundamental principles of its behavior. Here, we describe the transport, transformation, and bioavailability of SeNPs through a combination of in vivo and in vitro experiments. We show synthesized amorphous SeNPs, when sprayed onto the leaves of Arabidopsis thaliana, are rapidly biotransformed into selenium(IV), nonspecifically incorporated as selenomethionine (SeMet), and specifically incorporated into two selenium-binding proteins (SBPs). The SBPs identified were linked to stress and reactive oxygen species (mainly H2O2 and O2-) reduction, processes that enhance plant growth and primary root elongation. Selenium is transported both upwards and downwards in the plant when SeNPs are sprayed onto the leaves. With the application of Silwet L-77 (a common agrochemical surfactant), selenium distributed throughout the whole plant including the roots, where pristine SeNPs cannot reach. Our results demonstrate that foliar application of SeNPs promotes plant growth without causing nanomaterial accumulation, offering an efficient way to obtain selenium-fortified agriculture.