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The skin serves as a physical barrier and an immunological interface that protects the body from the external environment 1 – 3 . Aberrant activation of immune cells can induce common skin autoimmune diseases such as vitiligo, which are often characterized by bilateral symmetric lesions in certain anatomic regions of the body 4 – 6 . Understanding what orchestrates the activities of cutaneous immune cells at an organ level is necessary for the treatment of autoimmune diseases. Here we identify subsets of dermal fibroblasts that are responsible for driving patterned autoimmune activity, by using a robust mouse model of vitiligo that is based on the activation of endogenous auto-reactive CD8 + T cells that target epidermal melanocytes. Using a combination of single-cell analysis of skin samples from patients with vitiligo, cell-type-specific genetic knockouts and engraftment experiments, we find that among multiple interferon-γ (IFNγ)-responsive cell types in vitiligo-affected skin, dermal fibroblasts are uniquely required to recruit and activate CD8 + cytotoxic T cells through secreted chemokines. Anatomically distinct human dermal fibroblasts exhibit intrinsic differences in the expression of chemokines in response to IFNγ. In mouse models of vitiligo, regional IFNγ-resistant fibroblasts determine the autoimmune pattern of depigmentation in the skin. Our study identifies anatomically distinct fibroblasts with permissive or repressive IFNγ responses as the key determinant of body-level patterns of lesions in vitiligo, and highlights mesenchymal subpopulations as therapeutic targets for treating autoimmune diseases. Single-cell analyses of skin samples from patients with vitiligo and functional genetic experiments in vitiligo mouse models show that distinct fibroblast subsets drive the organ level lesion patterns in this autoimmune disease.

Vitiligo is the most common human skin depigmenting disorder. It is mediated by endogenous autoreactive CD8 + T cells that destruct skin melanocytes. This disease has an estimated prevalence of 1% of the global population and currently has no cure. Animal models are indispensable tools for understanding vitiligo pathogenesis and for developing new therapies. Here, we describe a vitiligo mouse model which recapitulates key clinical features of vitiligo, including epidermis depigmentation, CD8 + T cell infiltration in skin, and melanocyte loss. To activate endogenous autoreactive cytotoxic CD8 + T cells targeting melanocytes, this model relies on transient inoculation of B16F10 melanoma cells and depletion of CD4 + regulatory T cells. At cellular level, epidermal CD8 + T cell infiltration and melanocyte loss start as early as Day 19 after treatment. Visually apparent epidermis depigmentation occurs 2 months later. This protocol can efficiently induce vitiligo in any C57BL/6 background mouse strain, using only commercially available reagents. This enables researchers to carry out in-depth in vivo vitiligo studies utilizing mouse genetics tools, and provides a powerful platform for drug discovery.

Vitiligo, an autoimmune skin disorder characterized by melanocyte loss, has long been associated with sympathetic nervous system activity. Clinical observations have suggested links between psychological stress, sympathetic activation, and vitiligo progression. However, direct experimental evidence for the role of sympathetic nerves in vitiligo development has been lacking. Herein, we employed 6-hydroxydopamine (6-OHDA) to induce sympathetic nerve depletion in mice before vitiligo induction. Sympathetic nerve ablation was confirmed through immunofluorescent staining of tyrosine hydroxylase. Vitiligo progression was assessed by quantifying epidermal melanocytes and CD8+ T cells using whole-mount immunofluorescence staining. The loss of melanocytes and infiltration of CD8+ T cells in vitiligo lesions were comparable between sympathectomized and control mice. Overall, our study suggested that previously observed associations between sympathetic nervous system activity and vitiligo may be concomitant effects rather than causative factors, challenging long-held clinical hypotheses.

Silver nanoparticles (AgNPs) were synthesized through an environmentally friendly method with tea extract as a reduction agent. By immobilizing them on the surface of a low-cost pencil graphite electrode (PGE) with the aid of a simple and well-controlled in-situ electropolymerization method, a novel nanosensing interface for nitrite was constructed. The film-modified PGE showed good electrocatalytic effects on the oxidation of nitrite and was characterized through scanning electron microscopy, X-ray photoelectron spectroscopy, and electrochemical techniques. Characterization results clearly show that the successful modification of AgNPs improved the surface area and conductivity of PGEs, which is beneficial to the high sensitivity and short response time of the nitrite sensor. Under the optimal detection conditions, the oxidation peak current of nitrite had a good linear relationship with its concentration in the range of 0.02–1160 μmol/L with a detection limit of 4 nmol/L and a response time of 2 s. Moreover, the sensor had high sensitivity, a wide linear range, a good anti-interference capability, and stability and reproducibility. Additionally, it can be used for the determination of nitrite in food.

Purpose This study aimed to evaluate the impact of mind–body exercise (yoga, tai chi, qigong, etc.) on lung cancer. Methods We performed a literature search of the electronic databases PubMed, Web of Science, Cochrane Library, Embase, CNKI, CBM, WanFang Data, and VIP from their inception to 16 May 2023. The primary outcome was the 6-min walk test (6MWT), while the secondary outcomes were anxiety levels and quality of life (QoL). Two independent reviewers performed the data extraction using a predefined protocol and assessed the risk of bias using the Cochrane risk of bias (ROB) tool for randomized controlled trials, with differences agreed by consensus. Meta-analysis was performed using RevMan 5.4 and Stata 15 software to analyze the extracted data. Results This meta-analysis included a total of 11 studies involving 897 patients. The results indicated that compared to the usual care group, lung cancer patients in the mind–body exercise group could increase the 6-min walk distance (5 studies, 346 participants, WMD: 18.83, 95% CI (7.55, 30.10) P  = 0.001), reduce anxiety levels (4 studies, 362 participants, SMD: − 1.51, 95% CI (− 1.74, − 1.27), P  < 0.05), and enhance the overall quality of life (6 studies, 594 participants, SMD: 0.71, 95% CI (0.10, 1.31), P  = 0.02). The overall certainty of the evidence for all outcomes was low; seven studies were judged to be at low risk of bias, and four studies were judged to be at moderate risk of bias. Conclusion Mind–body exercise could improve exercise capacity in lung cancer survivors, reduce anxiety, and positively affect overall quality of life. PROSPERO registration number CRD42023426800

In the turning process of U-2Nb alloys, pearlite laminae parallel to the machined surface fractures easily at α phase and γ phase interface, resulting in a discontinuous chip breaking process, which leads to a large amount of damage produced on the workpiece surface. The damaged area will exhibit serious local corrosion behavior during the service process. Through surface rolling deformation treatment, the repair of machined damage can be completed, the smoothness and integrity of the workpiece surface can be further improved, and the microstructure of the surface layer can be refined. The local corrosion behavior of the repaired surface is obviously restrained, meanwhile a compact and stable oxide film that formed in the atmospheric environment can effectively prevent the further development of corrosion.

By foliar application of a range of methanol solutions (0, 2.5, 5, 7.5, 10 %, v/v) on leaves of salt-stressed soybean seedlings, and comparing changes in plant height and relative electrolytic leakage, the appropriate concentration of foliar methanol for mitigating of salt injury to soybean was selected. On this basis, foliar application of the appropriate concentration of methanol solution was conducted on salt-stressed soybean cv. Jackson (the salt-sensitive) and cv. Lee68 (the salt-tolerant) seedlings. By comparing changes in plant dry matter weight, leaf area and net photosynthetic rate (Pn), root and leaf thiobarbituric acid reactive substances (TBARS) contents, and plant Na⁺, K⁺contents and Na⁺/K⁺ratios, physiological effects of foliar methanol application were analyzed. The results showed that: Use of different concentrations of methanol solution for foliar spraying all had ameliorative effects for salt-treated soybean seedlings, of which, 5 % concentration was the appropriate. Under salt stress, plant dry matter weight, leaf area and Pn of cv. Jackson and cv. Lee68 seedlings decreased significantly, TBARS contents in roots and leaves were increased significantly, K⁺contents in soybean plants declined, while Na⁺contents and Na⁺/K⁺ratios increased remarkably, and as a whole, the changes in cv. Jackson were higher than those in cv. Lee68. Under salt stress plus leaf spraying of 5 % methanol, plant dry matter weight, K⁺contents, leaf area and Pn of cv. Jackson and Lee68 seedlings were restored, root and leaf TBARS contents, plant Na⁺contents and Na⁺/K⁺ratios were all reduced, of which cv. Jackson displayed a more pronounced effect.

This Paper proposes a novel Transformer-based end-to-end autonomous driving model named Detrive. This model solves the problem that the past end-to-end models cannot detect the position and size of traffic participants. Detrive uses an end-to-end transformer based detection model as its perception module; a multi-layer perceptron as its feature fusion network; a recurrent neural network with gate recurrent unit for path planning; and two controllers for the vehicle's forward speed and turning angle. The model is trained with an on-line imitation learning method. In order to obtain a better training set, a reinforcement learning agent that can directly obtain a ground truth bird's-eye view map from the Carla simulator as a perceptual output, is used as teacher for the imitation learning. The trained model is tested on the Carla's autonomous driving benchmark. The results show that the Transformer detector based end-to-end model has obvious advantages in dynamic obstacle avoidance compared with the traditional classifier based end-to-end model.

The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual’s genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of Eubacterium rectale in decreasing plasma levels of hydrogen sulfite—a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome. The influence of an individual’s genetics, diet and gut microbiome on their plasma metabolome was studied in 1,368 individuals and Mendelian randomization and mediation analyses were used to unveil causal relationships between diet, the gut microbiome and the metabolome.

Brown planthopper (BPH) is one of the most destructive insects affecting rice (Oryza sativa L.) production. Phenylalanine ammonialyase (PAL) is a key enzyme involved in plant defense against pathogens, but the role of PAL in insect resistance is still poorly understood. Here we show that expression of the majority of PALs in rice is significantly induced by BPH feeding. Knockdown of OsPALs significantly reduces BPH resistance, whereas overexpression of OsPAL8 in a susceptible rice cultivar significantly enhances its BPH resistance. We found that OsPALs mediate resistance to BPH by regulating the biosynthesis and accumulation of salicylic acid and lignin. Furthermore, we show that expression of OsPAL6 and OsPAL8 in response to BPH attack is directly up-regulated by OsMYB30, an R2R3 MYB transcription factor. Taken together, our results demonstrate that the phenylpropanoid pathway plays an important role in BPH resistance response, and provide valuable targets for genetic improvement of BPH resistance in rice.