Browse Articles

Decoding 4-vinylanisole biosynthesis and pivotal enzymes in locusts

Extensive digital health technology assessment detects subtle motor impairment in mild and asymptomatic Pompe disease

Nuclear-weapons risks are back — and we need to act like it

Quantum granular-ball generation methods and their application in KNN classification

Mystery of billions of sea-star deaths solved at last

Tiny motor uses heat to perform molecular magic

Molecular gradients shape synaptic specificity of a visuomotor transformation

Abstract How does the brain convert visual input into specific motor actions1,2? In Drosophila, visual projection neurons (VPNs)3,4 perform this visuomotor transformation by converting retinal positional information into synapse number in the brain5. The molecular basis of this phenomenon remains unknown. We addressed this issue in LPLC2 (ref. 6), a VPN type that detects looming motion and preferentially drives escape behaviour to stimuli approaching from the dorsal visual field with progressively weaker responses ventrally. This correlates with a dorsoventral gradient of synaptic inputs into and outputs from LPLC2. Here we report that LPLC2 neurons sampling different regions of visual space exhibit graded expression of cell recognition molecules matching these synaptic gradients. Dpr13 shapes LPLC2 outputs by binding DIP-ε in premotor descending neurons mediating escape. Beat-VI shapes LPLC2 inputs by binding Side-II in upstream motion-detecting neurons. Gain-of-function and loss-of-function experiments show that these molecular gradients act instructively to determine synapse number. These patterns, in turn, fine-tune the perception of the stimulus and drive the behavioural response. Similar transcriptomic variation within neuronal types is observed in the vertebrate brain7 and may shape synapse number via gradients of cell recognition molecules acting through both genetically hard-wired programs and experience.

Direct identification of Ac and No molecules with an atom-at-a-time technique

Eating ultra-processed foods could make it harder to lose weight

India to penalize universities with too many retractions

mRNA vaccines for HIV trigger strong immune response in people

Google AI model mines trillions of images to create maps of Earth ‘at any place and time’

Loss of colonic fidelity enables multilineage plasticity and metastasis

Abstract Cancer cell plasticity enables the acquisition of new phenotypic features and is implicated as a major driver of metastatic progression1,2. Metastasis occurs mostly in the absence of additional genetic alterations3–5, which suggests that epigenetic mechanisms are important6. However, they remain poorly defined. Here we identify the chromatin-remodelling enzyme ATRX as a key regulator of colonic lineage fidelity and metastasis in colorectal cancer. Atrx loss promotes tumour invasion and metastasis, concomitant with a loss of colonic epithelial identity and the emergence of highly plastic mesenchymal and squamous-like cell states. Combined analysis of chromatin accessibility and enhancer mapping identified impairment of activity of the colonic lineage-specifying transcription factor HNF4A as a key mediator of these observed phenotypes. We identify squamous-like cells in human patient samples and a squamous-like expression signature that correlates with aggressive disease and poor patient prognosis. Collectively, our study defines the epigenetic maintenance of colonic epithelial identity by ATRX and HNF4A as suppressors of lineage plasticity and metastasis in colorectal cancer.

Author Correction: Spatial immune scoring system predicts hepatocellular carcinoma recurrence

Extreme river flood exposes latent erosion risk

Abstract Climate change is expected to increase the frequency and magnitude of river floods 1 . Floods not only cause damage by inundation and loss of life 2,3 but also jeopardize infrastructure because of bank failure and riverbed erosion processes that are poorly understood. Common flood safety programmes include dyke reinforcement and river widening 4–9 . The 2021 flood in the Meuse Basin caused 43 fatalities and billions of dollars of damage to infrastructure 10 . Here, on the basis of analysis of the Meuse flood, we show how uneven widening of the river and heterogeneity of sediment deposits under the river can cause massive erosion. A recent flood safety programme widened the river 11 , but created bottlenecks where widening was either prevented by infrastructure or not yet implemented. Riverbed erosion was exacerbated by tectonic uplift that had produced a thin top gravel layer above fine-grained sediment. Greatly enhanced flow velocities produced underwater dunes with troughs that broke through the gravel armour in the bottlenecks, exposing easily erodible sands, resulting in extreme scour holes, one more than 15 m deep. Our investigation highlights the challenges of re-engineering rivers in the face of climate change, increased flood risks and competition for river widening space, and calls for a better understanding of the subsurface.

‘Sleeping’ cancer cells in the lungs can be roused by COVID and flu

Steel surface defect segmentation with SME-DeeplabV3+

Accurate segmentation of steel surface defects is crucial for ensuring steel quality. This paper presents a steel surface defect segmentation method based on SME-DeepLabV3+ to improve the accuracy and efficiency of segmentation. First, StarNet is adopted as the backbone network, whose unique star operation can achieve efficient transformation from low-dimensional space to high-dimensional features, enhancing the model’s ability to capture steel defect features and accurately distinguish between normal and defective areas. Second, the ELA module is introduced, which is based on an efficient local attention mechanism and uses different sizes of convolution kernels for multiscale analysis of feature maps. During training, it adaptively initializes the weights of convolutional layers and introduces a dynamic threshold adjustment mechanism to adjust thresholds in real time according to the defect conditions of training batches, reducing missed detections and false positives. Finally, we integrate the MSAA module from CM-UNet, whose multiscale attention mechanism can dynamically adjust attention allocation based on defect size, avoiding detection omissions or misjudgements caused by size differences. The experimental results show that the improved model performs excellently in steel surface defect segmentation tasks, significantly improving accuracy and efficiency compared with traditional methods. The mIoU, precision, and MPA evaluation metrics increased by 1.65%, 2.19%, and 0.36%, respectively, providing more effective technical support for steel quality inspection. The combination of StarNet with the MSAA and ELA modules effectively enhances the performance of semantic segmentation models in steel defect detection while reducing computational resource requirements. The code is available at https://github.com/Eric-863/SME-main/tree/main.

Analysis of adverse drug reactions in 507 cases of Tislelizumab: A real-world retrospective study based on data from Guangxi, China

Objective To analyze the real-world characteristics and patterns of adverse drug reactions (ADRs) associated with tislelizumab, providing valuable insights for clinical practice. Methods We conducted a comprehensive analysis of tislelizumab-related ADR reports within the pharmacovigilance system of Guangxi, China, spanning from 01/04/2021–31/08/2024. Our analysis focused on population characteristics, temporal distribution of ADR occurrences, system organ classes (SOCs) of serious adverse drug reactions (SADRs), profiles of major SOCs, and factors influencing SADRs and blood and lymphatic system disorders (BLSDs). Results This study analyzed 507 tislelizumab ADR reports (698 events), including 282 SADRs (356 events), with no deaths reported. Pharmacists were the primary reporters (60.55% of reports). Most patients were aged 46–75 years (77.32%), male (72.58%), and of Han ethnicity (75.54%), and 1.78% (9/507) were of Zhuang ethnicity. A total of 86.19% of ADRs occurred within 30 days of medication. Among the SADRs, there were 83 PTs and 17 SOCs, with the most common SOCs being blood and lymphatic system disorders (15.47%, 108/698), investigations (14.90%, 104/698), hepatobiliary disorders (4.15%, 29/698), and skin and subcutaneous tissue disorders (3.15%, 22/698). Logistic regression analysis showed that chemotherapy was a significant risk factor for SADRs (OR = 4.634, 95%CI: 2.871–7.917, P < 0.001). The risk of BLSDs - related ADRs was 5.545 times higher in the chemotherapy-incorporating group than in the monotherapy group (95%CI: 3.423–8.701, P < 0.001). Conclusions Close monitoring, particularly in patients receiving chemotherapy-incorporating regimens, is crucial during the first 30 days post-tislelizumab treatment to manage SADR risks. Proactive measures should be implemented if SADR occur.

Cannabidiol improves learning and memory deficits and alleviates anxiety in 12-month-old SAMP8 mice

Cannabidiol (CBD) has gained a lot of interest in recent years for its purported medicinal properties. CBD has been investigated for the treatment of anxiety, depression, epilepsy, neuroinflammation, and pain. Recently there has been an interest in CBD as a possible treatment for age-related disorders such as Alzheimer’s disease and related disorders (ADRD). Here we tested the hypothesis that chronic CBD administration would improve learning and memory in the SAMP8 mouse model of Alzheimer’s disease. SAMP8 mice aged 11 months (at the start of the study) were administered vehicle or CBD (3 or 30 mg/Kg) daily via oral gavage for 2 months. Vehicle-treated young SAMP8 mice (age 3 months at the start of the study) served as unimpaired controls. After 30 days of treatment (4 and 12 months of age), learning and memory, activity, anxiety, strength and dexterity were assessed. High dose CBD treatment significantly improved learning and memory of the 12-month-old mice in the T maze. Novel object recognition memory was also improved by CBD in aged CBD treated mice. Aged CBD treated mice also displayed less anxiety in the elevated plus maze test compared to controls. However, activity and strength levels were similar between groups. Biochemical analysis revealed decreased markers of oxidative stress, providing a possible mechanism by which CBD treatment impacts learning, memory, and anxiety. These results highlight the potential use of CBD as a therapeutic for age related cognitive impairment and dementia.

Numerical simulation and field experiment study of the supersonic gas jet subsoiler based on DEM

To tackle the challenges of high draft resistance, limited subsoiling range, and ineffective subsoiling results in conventional subsoiling methods, this study combines the structure of an air cannon with that of a wing-type subsoiler to design a novel pneumatic blast subsoiling device. First, soil bin experiments were conducted to verify the feasibility of using the air cannon for pneumatic soil fracturing. A soil model was created in EDEM (Engineering Discrete Element Method)based on field conditions to analyze the subsoiler’s force distribution, ensuring the nozzle remains undeformed and the subsoiling process runs smoothly. Subsequent field experiments were conducted to evaluate the subsoiling effect under different working depths, speeds, and air pressures. The experimental results show that, compared with the conventional airfoil-shaped subsoiler, the supersonic gas jet subsoiler achieves optimal performance at a tillage speed of 0.5 m/s and a tillage depth of 380 mm. Under these conditions, the maximum drag reduction rate reaches 16.66%, and the soil disturbance area increases by up to 22.48%, significantly enhancing the drag reduction effect and soil fragmentation efficiency during subsoiling operations. Furthermore, the subsoiling effect was further improved as the working speed decreased and the frequency of air blasts increased, satisfying the subsoiling operation assessment standards. In conclusion, this study offers design insights for the development of innovative agricultural soil cultivation tools by identifying a more efficient new research approach in addition to conventional subsoiling techniques for lowering resistance and energy consumption.