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Abstract Whilst reward pathologies are major and common in stress-related neuropsychiatric disorders, their neurobiology and treatment are poorly understood. Imaging studies in human reward pathology indicate attenuated BOLD activity in nucleus accumbens (NAc) coincident with reward anticipation but not reinforcement; potentially, this is dopamine (DA) related. In mice, chronic social stress (CSS) leads to reduced reward learning and motivation. Here, DA-sensor fibre photometry is used to investigate whether these behavioural deficits co-occur with altered NAc DA activity during reward anticipation and/or reinforcement. In CSS mice relative to controls: (1) Reduced discriminative learning of the sequence, tone-on + appetitive behaviour = tone-on + sucrose reinforcement, co-occurs with attenuated NAc DA activity throughout tone-on and sucrose reinforcement. (2) Reduced motivation during the sequence, operant behaviour = tone-on + sucrose delivery + sucrose reinforcement, co-occurs with attenuated NAc DA activity at tone-on and typical activity at sucrose reinforcement. (3) Reduced motivation during the sequence, operant behaviour = appetitive behaviour + sociosexual reinforcement, co-occurs with typical NAc DA activity at female reinforcement. Therefore, in CSS mice, low NAc DA activity co-occurs with low reward anticipation and could account for deficits in learning and motivation, with important implications for understanding human reward pathology.

Abstract Background Detection of cancer and identification of tumor origin at an early stage improve the survival and prognosis of patients. Herein, we proposed a plasma cfDNA-based approach called TOTEM to detect and trace the cancer signal origin (CSO) through methylation markers. Methods We performed enzymatic conversion-based targeted methylation sequencing on plasma cfDNA samples collected from a clinical cohort of 500 healthy controls and 733 cancer patients with seven types of cancer (breast, colorectum, esophagus, stomach, liver, lung, and pancreas) and randomly divided these samples into a training cohort and a testing cohort. An independent validation cohort of 143 healthy controls, 79 liver cancer patients and 100 stomach cancer patients were recruited to validate the generalizability of our approach. Results A total of 57 multi-cancer diagnostic markers and 873 CSO markers were selected for model development. The binary diagnostic model achieved an area under the curve (AUC) of 0.907, 0.908 and 0.868 in the training, testing and independent validation cohorts, respectively. With a training specificity of 98%, the specificities in the testing and independent validation cohorts were 100% and 98.6%, respectively. Overall sensitivity across all cancer stages was 65.5%, 67.3% and 55.9% in the training, testing and independent validation cohorts, respectively. Early-stage (I and II) sensitivity was 50.3% and 45.7% in the training and testing cohorts, respectively. For cancer patients correctly identified by the binary classifier, the top 1 and top 2 CSO accuracies were 77.7% and 86.5% in the testing cohort (n = 148) and 76.0% and 84.0% in the independent validation cohort (n = 100). Notably, performance was maintained with only 21 diagnostic and 214 CSO markers, achieving a training AUC of 0.865, a testing AUC of 0.866, and an integrated top 2 accuracy of 83.1% in the testing cohort. Conclusions TOTEM demonstrates promising potential for accurate multi-cancer detection and localization by profiling plasma methylation markers. The real-world clinical performance of our approach needs to be investigated in a much larger prospective cohort.

Abstract Cholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate the striatal network with glutamate and acetylcholine (ACh). In addition, VGLUT3-dependent glutamate increases ACh vesicular stores through vesicular synergy. A missense polymorphism, VGLUT3-p.T8I, was identified in patients with substance use disorders (SUDs) and eating disorders (EDs). A mouse line was generated to understand the neurochemical and behavioral impact of the p.T8I variant. In VGLUT3T8I/T8I male mice, glutamate signaling was unchanged but vesicular synergy and ACh release were blunted. Mutant male mice exhibited a reduced DA release in the dorsomedial striatum but not in the dorsolateral striatum, facilitating habit formation and exacerbating maladaptive use of drug or food. Increasing ACh tone with donepezil reversed the self-starvation phenotype observed in VGLUT3T8I/T8I male mice. Our study suggests that unbalanced dopaminergic transmission in the dorsal striatum could be a common mechanism between SUDs and EDs.

The effects of zinc addition on the general corrosion of 316L austenitic stainless steel and Stellite 6 cobalt-based alloy were studied in simulated pressurized water reactor primary water with 0, 10, and 40 μg·L–1 zinc additions. The corrosion rate and metal release rate of the two materials were determined by using the weight loss method. The surface and cross-sectional morphology, thickness, and element distribution of the oxide film were examined by scanning electron microscopy and transmission electron microscopy-energy dispersive spectroscopy (TEM-EDS). The crystallographic structures of the outer and inner oxides were identified by atomic-resolution TEM imaging with fast Fourier transform. The results reveal that the addition of 10 μg·L–1 Zn did not have a statistically significant effect on the corrosion rate and corrosion product release rate of 316L stainless steel within the initial 1000 h of exposure. Increasing the concentration of Zn to 40 μg·L–1 significantly reduced the corrosion rate, corrosion product release rate, and oxide film thickness of 316L stainless steel. Specifically, the oxide film thickness decreased from 250 to 95 nm. For the Stellite 6 cobalt-based alloy, composed of γ-Co matrix and Cr23C6 carbides, the galvanic corrosion effect between γ-Co matrix and Cr-rich carbides was observed under all zinc addition conditions. The oxide film thickness of Cr23C6 carbide in the Stellite 6 cobalt-based alloy was comparatively thinner than that of the γ-Co matrix, which is mainly ascribed to the preferential oxidation of the γ-Co matrix. Extensive interfacial oxidation was observed between γ-Co matrix and Cr23C6 carbide, which can be attributed to the occurrence of electrochemical galvanic corrosion between these two phases. The carbides have a higher nobility compared to the γ-Co matrix. The corrosion rate, corrosion product release rate, and oxide film thickness of Co-based alloy all decreased with increasing zinc concentrations. The average oxide film thickness of the preferentially oxidized γ-Co substrate decreased from 200 to 60 nm, and the average oxide film thickness of Cr23C6 carbide decreased from 100 to 40 nm. Microstructural analysis of the oxide film demonstrated that Zn2+ promotes the denser outer oxide film formation by forming a zinc-incorporated spinel, which retards the outward diffusion of metal ions and the inward diffusion of oxygen ions, reduces the oxygen partial pressure at the oxide/metal interface, and promotes the formation of a continuous protective Cr2O3 inner oxide film, thus significantly suppressing the corrosion and metal release of 316L austenitic stainless steel and Stellite 6 cobalt-based alloy in high-temperature water.

Abstract Acute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, the main immune cells and damage sensors of the CNS react to this injury and shape neuronal activity ex vivo. To this end, we investigated microglial phenotypes and contribution to network organization and functioning in acute brain slices. We reveal time-dependent microglial phenotype changes influenced by complex extracellular ATP dynamics through P2Y12R and CX3CR1 signalling, which is sustained for hours in ex vivo mouse brain slices. Downregulation of P2Y12R and changes of microglia-neuron interactions occur in line with alterations in the number of excitatory and inhibitory synapses over time. Importantly, functional microglia modulate synapse sprouting, while microglial dysfunction results in markedly impaired ripple activity both ex vivo and in vivo. Collectively, our data suggest that microglia are modulators of complex neuronal networks with important roles to maintain neuronal network integrity and activity. We suggest that slice preparation can be used to model time-dependent changes of microglia-neuron interactions to reveal how microglia shape neuronal circuits in physiological and pathological conditions.

201 Stainless steel and 5052 aluminium alloy were laser lap welded, both with and without a Ni foil interlayer. The Ni addition enhanced the metallurgical reaction between molten stainless steel/aluminium, resulting in the formation of the Al0.9Ni1.1 intermetallic compound. First-principles calculations estimated the equilibrium lattice and properties of IMCs (intermetallic compounds). A structural model of the interface revealed that the bonding strengths of Al/IMC and Fe/IMC interfaces surpassed those of IMC/IMC interfaces, making cracks prone to initiate and expand at the latter. Joints without Ni reached a max tensile shear strength of 74.5 N/mm, while those with Ni increased significantly to 101.8 N/mm, marking a substantial 36.6% enhancement.

Resistance seam welding additive manufacturing (RSAM) is a new solid-state additive manufacturing technique that utilizes pulsed current and pressure to welding powders layer by layer. In this study, Al1060 powder was employed as the raw material to prepare R0 and R10 samples through RSAM technology and subsequent repeated welding processes, respectively. The results showed that, compared to R0, the grain size of the R10 sample decreased from 34.3 μm to 8.7 μm, and the dislocation density increased from 4.355 × 1014 to 9.436 × 1014 m−2. Additionally, due to the additional heat and pressure from repeated welding, the porosity decreased from 0.998% to 0.017%, the ultimate tensile strength and elongation improved from 63.5 ± 0.5 MPa and 4.5 ± 0.1% in R0 to 93.3 ± 0.5 MPa and 34.3 ± 0.1% in R10. The improvement in mechanical properties is primarily due to the combined effects of grain refinement, dislocation strengthening, and pore self-healing. This study introduces a feasible new approach for additive manufacturing of aluminum alloys and other materials that is difficult to be additively manufactured by other methods.

Summary: Acetylcholine (ACh) is thought to play a role in driving the rapid, spontaneous brain-state transitions that occur during wakefulness; however, the spatiotemporal properties of cortical ACh activity during these state changes are still unclear. We perform simultaneous imaging of GRAB-ACh sensors, GCaMP-expressing basal forebrain axons, and behavior to address this question. We observed a high correlation between axon and GRAB-ACh activity around periods of locomotion and pupil dilation. GRAB-ACh fluorescence could be accurately predicted from axonal activity alone, and local ACh activity decreased at farther distances from an axon. Deconvolution of GRAB-ACh traces allowed us to account for sensor kinetics and emphasized rapid clearance of small ACh transients. We trained a model to predict ACh from pupil size and running speed, which generalized well to unseen data. These results contribute to a growing understanding of the precise timing and spatial characteristics of cortical ACh during fast brain-state transitions.

The thermodynamic properties of boron nitride under extreme pressures and temperatures are of great interest and importance for materials science and inertial confinement fusion physics, but they are poorly understood owing to the challenges of performing experiments and realizing ab initio calculations. Here, we report the first shock Hugoniot data on hexagonal boron nitride at pressures of 5–16 Mbar, using hohlraum-driven shock waves at the SGIII-p laser facility in China. Our density functional theory molecular dynamics calculations closely match experimental data, validating the equations of state for modeling the shock response of boron nitride and filling a crucial gap in the knowledge of boron nitride properties in the region of multi-Mbar pressures and eV temperatures. The results presented here provide fundamental insights into boron nitride under the extreme conditions relevant to inertial confinement fusion, hydrogen–boron fusion, and high-energy-density physics.

Background Recently, the effect of Lipoprotein(a) [Lp(a)] on thrombogenesis has aroused great interest, while inflammation has been reported to modify the Lp(a)-associated risks through an unidentified mechanism. Purpose This study aimed to evaluate the association between platelet reactivity with Lp(a) and high-sensitivity C-reactive protein (hs-CRP) levels in percutaneous intervention (PCI) patients treated with clopidogrel. Methods Data were collected from 10,724 consecutive PCI patients throughout the year 2013 in Fuwai Hospital. High on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) were defined as thrombelastography (TEG) maximum amplitude of adenosine diphosphate-induced platelet (MA ADP ) > 47 mm and

IntroductionWalnut green husk (WGH) is a waste byproduct from walnut industry. However, it is not well-known about its bioactive effect on human gut health.MethodsThis study conducted in vitro digestion and fermentation experiments to study the bioactive effect of WGH.ResultsMicrobial fermentation was the primary mechanism to efficiently release phenolics and flavonoids, resulting in more excellent antioxidant capacities (DPPH, ABTS, and FRAP assays), which reached a highest value with 14.82 ± 0.01 mg VcE/g DW, 3.47 ± 0.01 mmol TE/g DW, and 0.96 ± 0.07 mmol FeSO4·7H2O/g DW, respectively. The surface microstructure of WGH became loose and fragmented after microbial fermentation. The analytical results of gut microbiota demonstrated that WGH could significantly increase the relative abundance of Proteobacteria in phylum level and Phascolarctobacterium in genus level while certain pro-inflammatory bacteria (such as Clostridium_sensu_stricto_1, Dorea, Alistipes, and Bilophila) was inhibited. Additionally, 1,373 differential metabolites were identified and enriched in 283 KEGG pathways. Of which some metabolites were significantly upregulated including ferulic acid, chlorogenic acid, umbelliferone, scopolin, muricholic acid, and so forth.DiscussionThese results indicated that WGH could have antioxidant and anti-inflammatory activities in the human gut, which could improve the economical value of WGH in the food industry.

Abstract Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential to alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development of in-vivo applications for optochemistry to render brain cells photoresponsive without relying on genetic engineering has been progressing slowly. The nucleus accumbens (NAc) is a region for the regulation of slow-wave sleep (SWS) through the integration of motivational stimuli. Adenosine emerges as a promising candidate molecule for activating indirect pathway neurons of the NAc expressing adenosine A2A receptors (A2ARs) to induce SWS. Here, we developed a brain-permeable positive allosteric modulator of A2ARs (A2AR PAM) that can be rapidly photoactivated with visible light (λ > 400 nm) and used it optoallosterically to induce SWS in the NAc of freely behaving male mice by increasing the activity of extracellular adenosine derived from astrocytic and neuronal activity.

Abstract Steatotic liver disease (SLD) is a burgeoning health problem predominantly associated with excessive alcohol consumption, which causes alcohol-related liver disease (ALD), and high caloric intake, which results in metabolic dysfunction-associated SLD (MASLD). The pathogenesis of ALD and MASLD, which can progress from steatohepatitis to more severe conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma, is complicated by several factors. Recently, extracellular ATP and adenosine (Ado), as damage-associated molecular patterns, were reported to promote inflammation and liver fibrosis, contributing to SLD pathogenesis. Here, we explored the in vivo dynamics of hepatic extracellular ATP and Ado during the progression of steatohepatitis using a genetically encoded GPCR-activation-based sensor (GRAB) in zebrafish models. We established hepatocyte-specific GRABATP and GRABAdo in zebrafish and investigated the changes in in vivo hepatic extracellular ATP and Ado levels under ALD or MASLD conditions. Disease-specific changes in hepatocyte extracellular ATP and Ado levels were observed, clearly indicating a correlation between hepatocyte extracellular ATP/Ado dynamics and disease progression. Furthermore, clodronate, a vesicular nucleotide transporter inhibitor, alleviated the MASLD phenotype by reducing the hepatic extracellular ATP and Ado content. These findings provide deep insights into extracellular ATP/Ado dynamics in disease progression, suggesting therapeutic potential for ALD and MASLD.

In order to reveal the influence of special surface structures on the wetting and spreading of Ag/Ti system and the precursor film, micro-bumps, micro-pits, micro-grooves and micro-thread surface structures were machined on a grade 2 commercially-pure Ti (TA2) surface by using ultrafast laser. In situ wetting experiments of AgCuTi filler metal on TA2 surfaces with different special structures were conducted. The results showed that the wetting morphology of AgCuTi over original TA2 surface is special double ring (small circle inside and ring outside). The special surface structures can effectively change the wetting characteristics of Ag/Ti system, including the spreading rate and the final spreading area. It also affects the structure and composition of the wetting interface. In Ag/Ti system, different components are affected to different degrees by the surface structures, resulting in uneven distribution of the bulk liquid region and the precursor film region of the wetting interface. The micro-bumps and micro-pits structures can effectively promote the wetting and spreading of AgCuTi on TA2, while micro-thread structures can inhibit its wetting spread. For the micro-grooves, the AgCuTi spreads rapidly and almost completely along the direction of the groove, while in the vertical direction, it is difficult for the AgCuTi to spread through the groove. By studying the wetting spreading process and interface behavior of molten filler metal on complex surfaces, it is expected to provide important guiding significance for using special surface microstructure to control the wetting spreading process and interface reaction of brazing system.

Abstract The wide spread of Perfluoroalkyl substances (e.g., PFOA and PFOS) in soil can alter native soil geochemical properties and microbial communities through various approaches. Nonetheless, it is unclear that how PFOA and PFOS in soil affect the mineralization of soil organic carbon (SOC). A laboratory-scale culture experiment (180 d) was performed to explore the contribution of PFOA and PFOS to SOC dynamics and soil geochemical processes. Results showed that positive priming effect (PE) occurred in the short term (i.e., 30 days after PFOA and PFOS addition) and subsequently shifted to a slightly negative PE (i.e., 90 days) and remained in a significant negative PE thereafter (i.e., > 180 days). The PEs caused by PFOA and PFOS both accelerated the consumption of dissolved organic carbon (DOC), resulting in a significant increase in SOC mineralization (10.45%–127.36%) under the short-term incubation (30 d). As for long-term exposure (> 90 d), the organic carbon mineralization rate was significantly reduced (58.30%–65.24%) due to the excessive DOC consumption in the initial stage. High throughput analysis indicated that both PFOA and PFOS changed soil bacterial and fungal community structures, altered the relevant metabolic pathways and resulted in the enrichment of specific taxa. Graphical Abstract

A self-consistent and precise method to determine the time-dependent radiative albedo, i.e., the ratio of the reemission flux to the incident flux, for an indirect-drive inertial confinement fusion Hohlraum wall material is proposed. A specially designed symmetrical triple-cavity gold Hohlraum is used to create approximately constant and near-equilibrium uniform radiation with a peak temperature of 160 eV. The incident flux at the secondary cavity waist is obtained from flux balance analysis and from the shock velocity of a standard sample. The results agree well owing to the symmetrical radiation in the secondary cavity. A self-consistent and precise time-dependent radiative albedo is deduced from the reliable reemission flux and the incident flux, and the result from the shock velocity is found to have a smaller uncertainty than that from the multi-angle flux balance analysis, and also to agree well with the result of a simulation using the HYADES opacity.

The recently emerged Al–Mn–Mg–Sc–Zr alloys were regarded as high-strength Al alloys suitable for high-temperature applications. However, the influence of laser powder bed fusion (LPBF) fabricated anisotropic microstructure on tensile creep performance has not been explored. In this work, we reported an anisotropic tensile creep behavior, which is superior in the vertical specimens than the horizontal counterparts. The tensile creep anisotropy was attributed to the bi-modal microstructure of columnar grains within melt pool and equiaxed grains at melt pool boundary, the “fish-scale” melt pool morphology and the resulted tortuous crack path in the vertical orientation.

Abstract Background Coronary artery calcification (CAC) is a highly specific marker of atherosclerosis. Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are the therapeutic targets of ezetimibe and statins, respectively, which are important for the progression of atherosclerosis. However, CAC’s genetic susceptibility with above targets is still unknown. We aimed to investigate the association of NPC1L1 and HMGCR gene polymorphisms with CAC in patients with premature triple-vessel disease (PTVD). Methods Four single nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, rs2073547) of NPC1L1, and three SNPs (rs12916, rs2303151, rs4629571) of HMGCR were genotyped in 872 PTVD patients. According to the coronary angiography results, patients were divided into low-degree CAC group and high-degree CAC group. Results A total of 872 PTVD patients (mean age, 47.71 ± 6.12; male, 72.8%) were finally included for analysis. Multivariate logistic regression analysis showed no significant association between the SNPs of NPC1L1 and HMGCR genes and high-degree CAC in the total population (P > 0.05). Subgroup analysis by gender revealed that the variant genotype (TT/CT) of rs4720470 on NPC1L1 gene was associated with increased risk for high-degree CAC in male patients only (OR = 1.505, 95% CI: 1.008–2.249, P = 0.046) in dominant model, but no significant association was found in female population, other SNPs of NPC1L1 and HMGCR genes (all P > 0.05). Conclusions We reported for the first time that the rs4720470 on NPC1L1 gene was associated with high-degree CAC in male patients with PTVD. In the future, whether therapies related to this target could reduce CAC and cardiovascular events deserves further investigation.

Soil salinization is a critical issue impacting agriculture, particularly in arid and semi-arid regions. The objective of this study was to evaluate the effects of different drip irrigation and fertilization treatments on soil water and salt dynamics, maize water use efficiency, and crop yield in the saline–alkali soils of northern Ningxia, China. Over three years, four irrigation treatments were tested: CK (flood irrigation, 810 mm), W1 (low-volume drip irrigation, 360 mm), W2 (medium-volume drip irrigation, 450 mm), and W3 (high-volume drip irrigation, 540 mm). The results demonstrate that treatments W2 and W3 significantly increased soil moisture content at depths of 0–20 cm and 60–100 cm compared to CK, facilitating uniform salt leaching in the 0–40 cm soil layer. However, in the 40–100 cm layer, decreased porosity and upward moisture movement hindered salt migration, resulting in subsurface salt accumulation. Furthermore, drip irrigation combined with fertilization significantly reduced phosphorus fixation and nitrogen leaching, enhancing nutrient availability. This led to a reduction in underground leakage and surface evaporation by up to 39.63%, while water use efficiency improved by 18.97% to 55.13%. By the third year, grain yields under drip irrigation treatments increased significantly compared to CK, with W3 showing the highest gains (up to 21.90%). This study highlights the potential of integrating drip irrigation and fertilization as an effective strategy for managing saline–alkali soils, improving water use, and increasing crop productivity, providing valuable insights for sustainable agricultural practices.

Numerical analysis of the sediment erosion of the balance valve in a buoyancy regulation system was performed. A numerical model for the two-phase flow inside the balance valve was constructed based on the discrete phase model. The sediment erosion rate on the balance valve was discussed, and the effects of five parameters were considered. The effects of the sediment concentration and valve opening were found to be significant, while the effects of the pressure difference, sediment density, and size were found to be moderate. The erosion rate, according to the numerical results, increased linearly with the sediment concentration, so long-term operation of a buoyancy regulation system in high-concentration areas should be avoided. The erosion rate was the highest when the valve opening was 46.3%, so half-open operating conditions are not recommended. The erosion rate was proportional to the square root of the pressure difference. However, adjusting the pressure difference may not be an effective method for regulating the total erosion. The superposition of the secondary flow and the main stream caused particles to spiral along with the fluid, resulting in asymmetric erosion at the working edge. The erosion rate on the working edge decreased with the increase in the sediment size. Conversely, the erosion rate on the valve ball surface increased with the sixth power of the sediment size. Considering that large particles are more likely to cause a blockage, it is recommended to install a seawater pretreatment device at the inlet to prevent large sediments from entering the valve and to improve the working life of the buoyancy regulation system.

Honeysuckle, valued for its wide-ranging uses in medicine, cuisine, and aesthetics, faces a significant challenge in cultivation due to powdery mildew, primarily caused by the Erysiphe lonicerae pathogen. The interaction between honeysuckle and E. lonicerae, especially concerning disease progression, remains insufficiently understood. Our study, conducted in three different locations, found that honeysuckle naturally infected with E. lonicerae showed notable decreases in total flavonoid content, with reductions of 34.7%, 53.5%, and 53.8% observed in each respective site. Controlled experiments supported these findings, indicating that artificial inoculation with E. lonicerae led to a 20.9% reduction in flavonoid levels over 21 days, worsening to a 54.8% decrease by day 42. Additionally, there was a significant drop in the plant’s total antioxidant capacity, reaching an 81.7% reduction 56 days after inoculation. Metabolomic analysis also revealed substantial reductions in essential medicinal components such as chlorogenic acid, luteolin, quercetin, isoquercetin, and rutin. Investigating gene expression revealed a marked decrease in the relative expression of the LjPAL1 gene, starting as early as day 7 post-inoculation and falling to a minimal level (fold change = 0.29) by day 35. This trend was mirrored by a consistent reduction in phenylalanine ammonia-lyase activity in honeysuckle through the entire process, which decreased by 72.3% by day 56. Further analysis showed significant and sustained repression of downstream genes LjFNHO1 and LjFNGT1, closely linked to LjPAL1. We identified the mechanism by which E. lonicerae inhibits this pathway and suggest that E. lonicerae may strategically weaken the honeysuckle’s disease resistance by targeting key biosynthetic pathways, thereby facilitating further pathogen invasion. Based on our findings, we recommend two primary strategies: first, monitoring medicinal constituent levels in honeysuckle from E. lonicerae-affected areas to ensure its therapeutic effectiveness; and second, emphasizing early prevention and control measures against honeysuckle powdery mildew due to the persistent decline in crucial active compounds.

Background: Renal cell carcinoma is the most common form of kidney cancer which is a global threat to human health, needing to explore effective therapeutic targets and treatment methods. Aurora kinase B acts as an important carcinogenic role in various kinds of tumors, while its mechanism in renal cell carcinoma is indistinct. Herein we explore the underlying mechanism of Aurora kinase B in renal cell carcinoma. Methods and results: Label-free quantitative proteomics analysis was employed to analyze the differentially expressed proteins in 786-O cells which were treated with si-Aurora kinase B or si-ctrl. In the current study, 169 differentially expressed proteins were identified. The top 10 upregulated proteins were MX2, IFI44L, ISG20, DDX58, F3, IFI44, ECE1, PRIC285, NIT1, and IFIT2. The top 10 downregulated proteins were FKBP9, FSTL1, DDAH1, TGFB2, HMGN3, COIL, FAM65A, PTPN14, ARFGAP2, and EIF2C2. GO enrichment analysis showed that these differentially expressed proteins participated in biological processes, including defense response to virus, response to virus, and type I interferon signaling pathway. These differentially expressed proteins participated in cellular components, including focal adhesion, cell-substrate adherens junction, cell-substrate junction, and endoplasmic reticulum lumen. These differentially expressed proteins participated in molecule functions, including guanyl nucleotide binding, nucleotidase activity, double-stranded RNA binding, 2′-5′-oligoadenylate synthetase activity, and virus receptor activity. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the significantly changed proteins including OAS3, OAS2, JAK1, TAP1, and RAC1 were involved in Epstein-Barr virus infection. Conclusions: Taken together, our results demonstrate the possible mechanisms that Aurora kinase B may participate in renal cell carcinoma. These findings may provide insights into tumorigenesis and a theoretical basis for developing potential therapies of renal cell carcinoma.

Crop production is strongly impacted by soil nitrogen supply, which is regulated by soil micro-food webs consisting of nematodes, protists, fungi and bacteria. However, responses of soil micro-food webs to fertilization at the aggregate scale and their relationships with soil nitrogen supply and crop yield remain unclear. To address these knowledge gaps, we investigated soils subjected to typical fertilization treatments in a long-term field experiment, which included: no fertilizer control (CK); synthetic fertilizers (NPK); partial synthetic nitrogen replacement with pig slurry (OMNPK) or crop straw (RSDNPK) and incorporating biochar with synthetic fertilizers (BCNPK). The composition of different biological groups was changed significantly by fertilization, with bacteria under RSDNPK being more responsive than other groups. The co-occurrence network of the soil micro-food web had more edges in microaggregates than those in large and small macroaggregates due to the significantly higher nodal degree of bacteria and fungi. On average, 76 % of the topologically important (TI) taxa in the networks were bacteria. In modules where nematodes and protists were present, 8 %-100 % of them were attributed to TI taxa while the ratio for bacteria was 3 %-7 %. Specific assemblages of functionally important (FI) taxa covering all tested biological groups at the aggregate scale were positively associated with soil labile nitrogen, related enzymes and crop yield. Random forest regression further indicates the high importance of these FI taxa to crop yield. However, less than 20 % of them were attributed to TI taxa of the networks. In summary, distinct assemblages of taxa covering multiple trophic levels regulate network topology and soil nitrogen supply + crop yield, which provides insights for targeted manipulation of soil micro-food webs through knowledge-based fertilization to harness the biological potential of cropland soils.

Neurons of the basal forebrain nucleus basalis and posterior substantia innominata (NBM/SIp) comprise the major source of cholinergic input to the basolateral amygdala (BLA). Using a genetically encoded acetylcholine (ACh) sensor in mice, we demonstrate that BLA-projecting cholinergic neurons can ‘learn’ the association between a naive tone and a foot shock (training) and release ACh in the BLA in response to the conditioned tone 24 hr later (recall). In the NBM/SIp cholinergic neurons express the immediate early gene, Fos following both training and memory recall. Cholinergic neurons that express Fos following memory recall display increased intrinsic excitability. Chemogenetic silencing of these learning-activated cholinergic neurons prevents expression of the defensive behavior to the tone. In contrast, we show that NBM/SIp cholinergic neurons are not activated by an innately threatening stimulus (predator odor). Instead, VP/SIa cholinergic neurons are activated and contribute to defensive behaviors in response to predator odor, an innately threatening stimulus. Taken together, we find that distinct populations of cholinergic neurons are recruited to signal distinct aversive stimuli, demonstrating functionally refined organization of specific types of memory within the cholinergic basal forebrain of mice.

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward – even prior to reward delivery and in the absence of discrete stimuli. Photostimulation of basal forebrain cholinergic neurons, or their terminals in the basolateral amygdala (BLA), selectively promoted conditioned responding (licking), but not unconditioned behavior nor innate motor outputs. In vivo electrophysiological recordings during cholinergic photostimulation revealed reward-contingency-dependent suppression of BLA neural activity, but not prefrontal cortex. Finally, ex vivo experiments demonstrated that photostimulation of cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic receptor signaling, while also facilitating firing in BLA GABAergic interneurons. Taken together, we show that the neural and behavioral effects of basal forebrain cholinergic activation are modulated by reward contingency in a target-specific manner.

Summary: Meaningful auditory memories are formed in adults when acoustic information is delivered to the auditory cortex during heightened states of attention, vigilance, or alertness, as mediated by neuromodulatory circuits. Here, we identify that, in awake mice, acoustic stimulation triggers auditory thalamocortical projections to release adenosine, which prevents cortical plasticity (i.e., selective expansion of neural representation of behaviorally relevant acoustic stimuli) and perceptual learning (i.e., experience-dependent improvement in frequency discrimination ability). This sound-evoked adenosine release (SEAR) becomes reduced within seconds when acoustic stimuli are tightly paired with the activation of neuromodulatory (cholinergic or dopaminergic) circuits or periods of attentive wakefulness. If thalamic adenosine production is enhanced, then SEAR elevates further, the neuromodulatory circuits are unable to sufficiently reduce SEAR, and associative cortical plasticity and perceptual learning are blocked. This suggests that transient low-adenosine periods triggered by neuromodulatory circuits permit associative cortical plasticity and auditory perceptual learning in adults to occur.

ObjectiveAntiseizure medications (ASMs) are first line therapy for seizure disorders. Their effects on arrhythmias, especially the risk of arrhythmias associated with lacosamide (LCM), levetiracetam (LEV), and perampanel (PER), have been intensely investigated.MethodsWe searched four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) until August 6, 2023. We used a common effects model and reported data as pooled incidence with 95% CIs. Meta-analyses were conducted to elucidate the risk of arrhythmias with different drugs, and Egger’s regression was performed to detect publication bias analysis.ResultsWe included 11 clinical trials with 1,031 participants. The pooled incidence of arrhythmias in the LEV group was 0.005 (95% CI: 0.001-0.013), while it was 0.014 in the LCM group (95% CI: 0.003-0.030). Publication bias analyses indicated no significant bias in the LEV group (t = 0.02, df = 4, p-value = 0.9852) but a significant bias in the LCM group (t = 5.94, df = 3, p-value = 0.0095). We corrected for this bias in the LCM group using the trim-and-fill method, which yielded a similar pooled incidence of 0.0137 (95% CI: 0.0036-0.0280), indicating good reliability. Due to insufficient studies, we could not conduct a meta-analysis for PER, and we analyzed them in our systematic review.ConclusionThe use of LCM significantly elevated the risk of arrhythmias, while LEV had non-significant arrhythmogenic effects. As for the arrhythmogenic effects of PER, more clinical trials are needed in the future.

In order to address the issues of significant energy and resource waste, low-energy management efficiency, and high building-maintenance costs in hot-summer and cold-winter regions of China, a research project was conducted on an office building located in Nantong. In this study, a data-driven golden jackal optimization (GJO)-based Long Short-Term Memory (LSTM) short-term energy-consumption prediction and optimization system is proposed. The system creates an equivalent model of the office building and employs the genetic algorithm tool Wallacei to automatically optimize and control the building’s air conditioning system, thereby achieving the objective of reducing energy consumption. To validate the authenticity of the optimization scheme, unoptimized building energy consumption was predicted using a data-driven short-term energy consumption-prediction model. The actual comparison data confirmed that the reduction in energy consumption resulted from implementing the air conditioning-optimization scheme rather than external factors. The optimized building can achieve an hourly energy saving rate of 6% to 9%, with an average daily energy-saving rate reaching 8%. The entire system, therefore, enables decision-makers to swiftly assess and validate the efficacy of energy consumption-optimization programs, thereby furnishing a scientific foundation for energy management and optimization in real-world buildings.

The investigation of iron under high pressure and temperatures is crucial to understand the Earth’s core structure and composition and the generation of magnetic fields. Here, we present new in situ XRD measurements for iron in an off-Hugoniot state by laser-driven ramp compression at pressure of 200–238 GPa. The lattice parameters for the hexagonal (hcp)-Fe phase and the c/a ratios were obtained to compare them with previous static and dynamical data, which provides the direct confirmation of such parameters via the different compression paths and strain rates. This work indicates that laser ramp compression can be utilized to provide crystal structure information and direct key information on the crystal structure of Fe at the ultrahigh pressure–temperature conditions relevant for planetology.

A Q345 steel butt-welded joint was manufactured using laser–arc hybrid welding (LAHW) technology, and its microstructure, microhardness, and residual stress (RS) distribution were measured. Using ABAQUS software, a sequentially coupled thermo-metallurgical-mechanical finite element method was employed to model the welding RS distribution in the LAHW joint made of Q345 steel. The effects of solid-state phase transformation (SSPT) and transverse restraint on the welding RS distribution were explored. The results show that a large number of martensite phase transformations occurred in the fusion zone and heat-affected zone of the LAHW joint. Furthermore, the SSPT had a significant effect on the magnitude and distribution of RS in the LAHW joint made of Q345 steel, which must be taken into account in numerical simulations. Transverse restraints markedly increased the transverse RS on the upper surface, with a comparatively minor impact on the longitudinal RS distribution. After the transverse restraint was released, both the longitudinal and transverse RS distributions in the LAHW joint reverted to a level akin to that of the welded joint under free conditions.

DNA polymerase β (DNA polymerase beta (POLB)) belongs to a member of the DNA polymerase X family, mainly involved in various biological metabolic processes, such as eukaryotic DNA replication, DNA damage repair, gene recombination, and cell cycle regulation. In this study, the muscle development-related gene POLB was screened by selection signature and RNA-seq analysis and then validated for the proliferation and apoptosis of bovine primary myocytes. It was also found that overexpression of the POLB gene had a pro-apoptosis effect, but interfering with the expression of the gene had no significant effect on cells. Then, the analysis of related apoptotic genes revealed that POLB overexpression affected CASP9 gene expression.

Sufficient conditions are obtained for a signed maximum principle for boundary value problems for Riemann–Liouville fractional differential equations with analogues of Neumann or periodic boundary conditions in neighborhoods of simple eigenvalues. The primary objective is to exhibit four specific boundary value problems for which the sufficient conditions can be verified. To show an application of the signed maximum principle, a method of upper and lower solutions coupled with monotone methods is developed to obtain sufficient conditions for the existence of a maximal solution and a minimal solution of a nonlinear boundary value problem. A specific example is provided to show that sufficient conditions for the nonlinear problem can be realized.

Carbon/Carbon (C/C) composites exhibit excellent mechanical properties at high temperatures, making them widely used in aerospace, such as the leading edges of spaceplane wings and the nose cones of hypersonic aircraft. However, damage caused by rain erosion to C/C composites affects their mechanical properties and poses significant challenges during operational service periods. A jet impingement test platform was employed to conduct single and multiple water-jet erosion tests on three-dimensional orthogonal C/C composite materials and to investigate the residual mechanical properties of the specimens after jet impact. The damage was characterized using optical microscopy, scanning electron microscopy, and X-ray computed tomography. The results showed that the damage types of the C/C composite materials under water-jet impingement included fiber bundle fracturing, delamination, and debonding. The extent of erosion damage was positively correlated with the jet velocity and diameter. The changes in the multi-jet damage indicated a cumulative expansion process, and z-directional fiber bundles exhibited superior resistance to jet impact damage propagation. The results of the three-point bending tests showed that the greater the initial impact damage, the lower the residual mechanical properties of the materials, and the residual strength of the specimen suddenly decreased when damage occurred at the back of the specimen.

This study explores the professional development (PD) of rural teachers in China based on their relationship with "left-behind" children, guided by two research questions: 1) How do rural teachers describe their relationship with left-behind children? and 2) How do rural teachers perceive the influence of their relationship with left-behind children on PD? The study revealed that Chinese rural school teachers experienced complex teacher-student relationships, both positive and negative, with left-behind children. Essentially, this study found that rural teachers are more likely to experience negative, conflict-ridden teacher-student relationships that can be attributed to left-behind children's psychological or behavioural problems, lack of support from parents of rural children, respect and understanding, as well as rural schools' inappropriate educational and management methods. However, the current study is not aimed at criticising the negative impact of teacher-student relationships on rural teachers' PD. Instead, it argues that by reflecting the challenges of teacher-student relationship with regard to left-behind children, rural teachers have become reflective and critically reflective practitioners to improve their PD. This finding enriches the understanding of how teacher-student relationships influence rural teachers' PD, and also provides recommendations from multiple dimensions to enhance these teachers' PD and education.

Objective: Challenging differential diagnosis Background: Occult breast cancer (OBC) is diagnosed when regional or distant metastases are found without evidence of a primary tumor. The low overall incidence is a great challenge for the management strategy of OBC. Aggressive diagnosis and personalized treatment are feasible treatment strategies for OBC. We report the case of an OBC patient who achieved pathological complete response (pCR) after neoadjuvant chemotherapy. Case Report: A 43-year-old woman was admitted to the hospital 6 months after detecting a lump in her left axilla, about the size of a quail egg, but not red or swollen, and the lump gradually grew. Mammography, ultrasound, and magnetic resonance imaging showed a visible left axilla lesion but no nodules in bilateral breasts. A core-needle biopsy of the axilla lesion revealed an invasive carcinoma of breast origin. The tumor cells were estrogen receptors (ER)-negative, progesterone receptor (PR)-negative, and HER2-positive (3+) by immunohistochemistry. The patient was finally diagnosed with HER2-positive, hormone receptor-negative occult breast cancer of the left breast, cT0N2M0, stage IIIA. The TCbHP regimen (docetaxel, carboplatin, trastuzumab, and pertuzumab) as neoadjuvant chemotherapy was given. She underwent a modified radical mastectomy, showing a pCR. Subsequent radiotherapy and HER2-targeted therapy were administrated. Conclusions: This case highlights that even aggressive HER2-positive breast cancer can present as an occult primary tumor. Our clinical experience suggests that neoadjuvant chemotherapy followed by modified radical mastectomy can be effective for treating such rare cases. The patient achieved pCR, which can provide a therapeutic strategy for effective treatment of similar OBCs [ABSTRACT FROM AUTHOR]