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The evolutionarily conserved catabolic process of autophagy involves the degradation of cytoplasmic components through lysosomal enzymes. Basal levels of autophagy maintain cellular homeostasis and under stress conditions high levels of autophagy are induced. It is often under such stress conditions that high levels of autophagy and cell death have been observed, leading to the idea that autophagy may act as an executioner of cell death. However the notion of autophagy as a cell death mechanism has been controversial and remains mechanistically undefined. There is now growing evidence that in specific contexts autophagy can indeed facilitate cell death. The pro‐death role of autophagy is however complicated due to the extensive cross‐talk between different signalling pathways. This review summarises the examples of where autophagy acts as a means of cell death and discusses the association of autophagy with the different cell death pathways. The January 2015 issue contains a Special Feature on Autophagy and Immunity. Autophagy is an essential process to maintain cellular homeostasis and functions. It is responsible for the lysosome‐mediated degradation of damaged proteins and organelles, and dysregulation of this pathway contributes to the development of a variety of diseases in man, including: diabetes, neurodegeneration and cancer. Recent studies have illuminated the importance of the regulatory pathways that control autophagy and the wide range of physiological processes it regulates in humans. Immunology and Cell Biology thanks the coordinators of this Special Feature ‐ Jim Harris and Justine Mintern ‐ for their planning and input. Further background information on this important topic is available through the accompanying web focus which links to related articles from across Nature Publishing Group.

Current researches on sodium penetration in electrolytic aluminum cathode carbon blocks primarily measure cathode expansion curves, showing mostly macroscopic characteristics. However, the microscopic structure is often underexplored. As a porous medium, the diffusion performance of cathode carbon blocks is closely tied to their internal pore structure. Viewing the cathode carbon block as a multiphase composite material, this study examines the sodium diffusion process from a microstructural perspective. A prediction model for sodium diffusion, considering factors like porosity, temperature, binding effects, current density, and molecular ratio, was developed. A random aggregate model was implemented in Python and imported into finite element software to simulate sodium diffusion using Fick’s second law. Results indicate that increased porosity, higher temperatures, reduced binding effects, increased current density, and higher molecular ratios enhance sodium infiltration, reducing diffusion resistance and increasing the diffusion coefficient. The simulation aligns well with experimental results, confirming its accuracy and reliability.

Tigecycline is a last-resort antibiotic to treat complicated infections caused by multidrug-resistant pathogens, while the emergence of plasmid-mediated tet (X) family severely compromises its clinical efficacy. Novel antimicrobial strategies not limited to new antibiotics in pharmaceutical pipeline are urgently needed. Herein, we reveal the metabolic disparities between tet (X)-negative and -positive E. coli , including distinct energy demand patterns under tigecycline exposure. In particular, the cysteine and methionine metabolism pathway is remarkably downregulated in tet (X)-positive bacteria. More importantly, we find that the addition of exogenous L-methionine (Met) effectively resensitizes tet (X)-positive pathogens to tigecycline. Our mechanistic analysis demonstrates that exogenous Met promotes intracellular tigecycline accumulation by upregulating bacterial proton motive force. Moreover, Met accelerates the conversion to S-adenosyl-L-methionine, an essential methyl donor, thereby enhancing 5mC methylation modification in the promoter region of tet (X4) gene and reducing its expression. Consistently, the potentiation of Met to tigecycline is abolished in tet (X4)-carrying E. coli Δ dcm but restored in dcm -complementary bacteria, which encodes DNA-cytosine methyltransferase. In multiple animal models of infection, Met markedly potentiates the effectiveness of tigecycline against pathogenic E. coli and K. pneumoniae . Overall, this work highlights the therapeutic potential of Met in overcoming plasmid-mediated high-level tigecycline resistance, and provides a new paradigm to enhance antibiotic efficacy by harnessing cellular metabolic networks as well as epigenetic modifications. The dissemination of plasmid-encoded tigecycline resistance gene tet (X) poses a global threat to public health, necessitating the development of innovative strategies. Here, the authors reveal that the supplementation of L-methionine not only facilitates intracellular accumulation of tigecycline but also reduces tet (X) expression by augmenting the 5mC methylation modification in its promoter region, thereby overcoming plasmid-mediated high-level tigecycline resistance.

Complex animal behaviors arise from a flexible combination of stereotyped motor primitives. Here we use the escape responses of the nematode Caenorhabditis elegans to study how a nervous system dynamically explores the action space. The initiation of the escape responses is predictable: the animal moves away from a potential threat, a mechanical or thermal stimulus. But the motor sequence and the timing that follow are variable. We report that a feedforward excitation between neurons encoding distinct motor states underlies robust motor sequence generation, while mutual inhibition between these neurons controls the flexibility of timing in a motor sequence. Electrical synapses contribute to feedforward coupling whereas glutamatergic synapses contribute to inhibition. We conclude that C. elegans generates robust and flexible motor sequences by combining an excitatory coupling and a winner-take-all operation via mutual inhibition between motor modules.

Advanced volumetric imaging methods and genetically encoded activity indicators have permitted a comprehensive characterization of whole brain activity at single neuron resolution in Caenorhabditis elegans . The constant motion and deformation of the nematode nervous system, however, impose a great challenge for consistent identification of densely packed neurons in a behaving animal. Here, we propose a cascade solution for long-term and rapid recognition of head ganglion neurons in a freely moving C. elegans . First, potential neuronal regions from a stack of fluorescence images are detected by a deep learning algorithm. Second, 2-dimensional neuronal regions are fused into 3-dimensional neuron entities. Third, by exploiting the neuronal density distribution surrounding a neuron and relative positional information between neurons, a multi-class artificial neural network transforms engineered neuronal feature vectors into digital neuronal identities. With a small number of training samples, our bottom-up approach is able to process each volume—1024 × 1024 × 18 in voxels—in less than 1 second and achieves an accuracy of 91% in neuronal detection and above 80% in neuronal tracking over a long video recording. Our work represents a step towards rapid and fully automated algorithms for decoding whole brain activity underlying naturalistic behaviors.

Background Hemophagocytic lymphohistiocytosis is a life-threatening hyperinflammatory syndrome resulting from uncontrolled activation of T cells and macrophages, frequently leading to multiorgan failure. Severe lactic acidosis (lactate ≥ 10 mmol/L), a rare yet critical manifestation, poses unique diagnostic and therapeutic challenges in the intensive care unit. Here, we report two cases of Chinese men with hemophagocytic lymphohistiocytosis presenting with extreme lactic acidosis, highlighting the necessity of early hemophagocytic lymphohistiocytosis screening in intensive care unit patients with unexplained hyperlactatemia. Case presentation Case 1: A 43-year-old Chinese male with diffuse large B cell lymphoma developed hemophagocytic lymphohistiocytosis, presenting with lactate 14.2 mmol/L, cytopenia, and hyperferritinemia. Etoposide therapy rapidly normalized lactate levels (within 24 hours) and led to complete recovery after autologous stem cell transplantation. Case 2: A 60-year-old Chinese male with chronic gout and soft tissue infection developed septic shock and reactive hemophagocytic lymphohistiocytosis (lactate 14.3 mmol/L). Despite initial response to etoposide, he succumbed to invasive aspergillosis due to treatment-related immunosuppression. Conclusion Extreme lactic acidosis in intensive care unit patients should prompt urgent hemophagocytic lymphohistiocytosis evaluation, particularly in Chinese populations. Etoposide is effective for malignancy-associated hemophagocytic lymphohistiocytosis, while reactive hemophagocytic lymphohistiocytosis may require tailored immunosuppression with strict infection prophylaxis. Routine reporting of patient ethnicity aids epidemiological understanding of rare diseases such as hemophagocytic lymphohistiocytosis.

The 24 GHz continuous-wave (CW) Doppler radar sensor (DRS) is widely used for measuring the instantaneous speed of moving objects by using a non-contact approach, and has begun to be used in train-borne movable speed measurements in recent years in China because of its advanced performance. The architecture and working principle of train-borne DRSs with different structures including single-channel DRSs used for freight train speed measurements in railway freight dedicated lines and dual-channel DRSs used for speed measurements of high-speed and urban rail trains in railway passenger dedicated lines, are first introduced. Then, the disadvantages of two traditional speed calibration methods for train-borne DRS are described, and a new speed calibration method based on the Doppler shift signal simulation by imposing a signal modulation on the incident CW microwave signal is proposed. A 24 GHz CW radar target simulation system for a train-borne DRS was specifically realized to verify the proposed speed calibration method for a train-borne DRS, and traceability and performance evaluation on simulated speed were taken into account. The simulated speed range of the simulation system was up to (5~500) km/h when the simulated incident angle range was within the range of (45 ± 8)°, and the maximum permissible error (MPE) of the simulated speed was ±0.05 km/h. Finally, the calibration and uncertainty evaluation results of two typical train-borne dual-channel DRS samples validated the effectiveness and feasibility of the proposed speed calibration approach for a train-borne DRS with full range in the laboratory as well as in the field.

Foveal hypoplasia is the major cause of visual loss. Here we report an isolated foveal hypoplasia patient without nystagmus. It is very rare, and its etiology is not completely understood. Using whole-exome sequencing and foveal hypoplasia-related gene filtering from a family with two generations, we identified a novel variant c.859T>C (p.S287P) and a rare non-frameshift variant c.229_230insGGG (p.Arg77_Glu78insGly) in the tyrosinase (TYR) gene that co-segregated in the affected member of this family. The compound heterozygous variants inherited in the proband were confirmed by Sanger sequencing and predicted from in silico studies to have an effect on protein function. In conclusion, our finding extends the spectrum of TYR variants and supports the important role of TYR in the development of eyes.

In rice pest management, accurate pest detection is critical for intelligent agricultural systems, yet challenges like limited dataset availability, pest occlusion, and insufficient small object detection accuracy hinder effective monitoring. To address the aforementioned challenges, this study presents YOLO-PEST, an innovative detection approach based on the YOLOv5s architecture to address these issues. YOLO-PEST collects rice pest images from multiple channels and images are randomly cropped to occlude detection boxes, effectively simulating pest overlapping scenarios. During the feature fusion process, the ConvNeXt module is integrated to improve the detection accuracy for small objects via multiscale feature extraction. Additionally, the CoTAttention mechanism is incorporated to enhance the model’s robustness under complex environmental conditions. Comparative experiments show that the YOLO-PEST approach achieves a 97% of mAP@0.5, representing a 1.4-point improvement compared with previous methods, thus verifying its effectiveness in rice pest management.

Psoriasis, a chronic inflammatory dermatosis, represents a significant clinical challenge due to its complex pathogenesis and the limitations of existing therapeutic strategies. Current psoriasis diagnoses are primarily clinician-dependent, with instrumental diagnostics serving as adjuncts. Ongoing research is progressively deciphering its molecular underpinnings; the future of psoriasis diagnostics may involve genetic and immunological profiling to pinpoint biomarkers, enabling more accurate and timely interventions. The administration of psoriasis medications, whether oral, injectable, or topical, is associated with a range of side effects and compliance issues. Topical medications, despite their advantages in patient compliance and reduced systemic side effects, are hindered by the altered skin barrier in psoriasis, which impedes effective drug penetration and retention. In recent years, the development of novel transdermal drug delivery systems represents a promising frontier in psoriasis management. Nanotechnology-, microneedle- and dressing-based systems have demonstrated the potential for improved skin penetration, enhanced bioavailability, or extended retention time. Here, we will focus on the latest insights into the etiology, diagnostic methodologies, and therapeutic approaches for psoriasis, with a particular emphasis on the evolution and challenges of novel transdermal drug delivery systems.