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The autonomic nervous system orchestrates the functions of the brain and body through the sympathetic and parasympathetic pathways 1 . However, our understanding of the autonomic system, especially the sympathetic system, at the cellular and molecular levels is severely limited. Here we show topological representations of individual visceral organs in the major abdominal sympathetic ganglion complex. Using multi-modal transcriptomic analyses, we identified molecularly distinct sympathetic populations in the coeliac–superior mesenteric ganglia (CG–SMG). Of note, individual CG–SMG populations exhibit selective and mutually exclusive axonal projections to visceral organs, targeting either the gastrointestinal tract or secretory areas including the pancreas and bile tract. This combinatorial innervation pattern suggests functional segregation between different CG–SMG populations. Indeed, our neural perturbation experiments demonstrated that one class of neurons regulates gastrointestinal transit, and another class of neurons controls digestion and glucagon secretion independent of gut motility. These results reveal the molecularly diverse sympathetic system and suggest modular regulation of visceral organ functions by sympathetic populations. Multi-modal transcriptomic analyses of the sympathetic nervous system reveal organ-specific neural innervation and modular regulation of visceral functions.

A large qubit capacity and an individual readout capability are two crucial requirements for large-scale quantum computing and simulation 1 . As one of the leading physical platforms for quantum information processing, the ion trap has achieved a quantum simulation of tens of ions with site-resolved readout in a one-dimensional Paul trap 2 – 4 and of hundreds of ions with global observables in a two-dimensional (2D) Penning trap 5 , 6 . However, integrating these two features into a single system is still very challenging. Here we report the stable trapping of 512 ions in a 2D Wigner crystal and the sideband cooling of their transverse motion. We demonstrate the quantum simulation of long-range quantum Ising models with tunable coupling strengths and patterns, with or without frustration, using 300 ions. Enabled by the site resolution in the single-shot measurement, we observe rich spatial correlation patterns in the quasi-adiabatically prepared ground states, which allows us to verify quantum simulation results by comparing the measured two-spin correlations with the calculated collective phonon modes and with classical simulated annealing. We further probe the quench dynamics of the Ising model in a transverse field to demonstrate quantum sampling tasks. Our work paves the way for simulating classically intractable quantum dynamics and for running noisy intermediate-scale quantum algorithms 7 , 8 using 2D ion trap quantum simulators. In this work, stable trapping of a two-dimensional Wigner crystal of above 500 ions is achieved, and the quantum simulation of 300 ions with individual state detection demonstrated.

Objectives To assess whether combination therapy with infliximab (IFX) plus nonsteroidal anti-inflammatory drugs (NSAIDs) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society (ASAS) partial remission in patients with early, active axial spondyloarthritis (SpA) who were naïve to NSAIDs or received a submaximal dose of NSAIDs. Methods Patients were randomised (2 : 1 ratio) to receive naproxen (NPX) 1000 mg daily plus either IFX 5 mg/kg or placebo (PBO) at weeks 0, 2, 6, 12, 18 and 24. The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28. Several other measures of disease activity, clinical symptoms and patient-rated outcomes were evaluated. Treatment group differences were analysed with Fisher exact tests or analysis of covariance. Results A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group (61.9%; 65/105) than in the PBO+NPX group (35.3%; 18/51) at week 28 (p=0.002) and at all other visits (p<0.05, all comparisons). Results of most other disease activity and patient-reported endpoints (including Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, multiple quality of life measures and pain measures) showed greater improvement in the IFX+NPX group than the PBO+NPX group, with several measures demonstrating early and consistent improvement over 28 weeks of treatment. Conclusions Patients with early, active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone. NPX alone led to clinical remission in a third of patients.

LncRNAs have critical roles in various biological processes ranging from embryonic development to human diseases, including cancer progression, although their detailed mechanistic functions remain illusive. The lncRNA linc-ROR has been shown to contribute to the maintenance of induced pluripotent stem cells and embryonic stem cells. In this study, we discovered that linc-ROR was upregulated in breast tumor samples, and ectopic overexpression of linc-ROR in immortalized human mammary epithelial cells induced an epithelial-to-mesenchymal transition (EMT) program. Moreover, we showed that linc-ROR enhanced breast cancer cell migration and invasion, which was accompanied by generation of stem cell properties. Contrarily, silencing of linc-ROR repressed breast tumor growth and lung metastasis in vivo . Mechanistically, our data revealed that linc-ROR was associated with miRNPs and functioned as a competing endogenous RNA to mi-205. Specifically, linc-ROR prevented the degradation of mir-205 target genes, including the EMT inducer ZEB2. Thus our results indicate that linc-ROR functions as an important regulator of EMT and can promote breast cancer progression and metastasis through regulation of miRNAs. Potentially, the findings of this study implicate the relevance of linc-ROR as a possible therapeutic target for aggressive and metastatic breast cancers.

Olfactory ensheathing cells (OECs) are glia reported to sustain the continuous axon extension and successful topographic targeting of the olfactory receptor neurons responsible for the sense of smell (olfaction). Due to this distinctive property, OECs have been trialed in human cell transplant therapies to assist in the repair of central nervous system injuries, particularly those of the spinal cord. Though many studies have reported neurological improvement, the therapy remains inconsistent and requires further improvement. Much of this variability stems from differing olfactory cell populations prior to transplantation into the injury site. While some studies have used purified cells, others have used unpurified transplants. Although both preparations have merits and faults, the latter increases the variability between transplants received by recipients. Without a robust purification procedure in OEC transplantation therapies, the full potential of OECs for spinal cord injury may not be realised.

Native to Mexico, Persea americana Mill. (avocado) is a fruit tree whose different parts (leaf, bark, roots, and stone) are used in traditional medicine especially against diabetes mellitus. The aim of this study was to investigate the beneficial effects of 28-day treatment with aqueous, ethanolic, and methanolic leaf extracts on glucose homeostasis in type 2 diabetic mellitus using Wistar rats. Type 2 diabetes was induced with nicotinamide (120 mg/kg, i.p.) and streptozotocin (65 mg/kg, i.p.). After 28 days of treatment, histopathological examination of the pancreas, kidneys, liver, and muscle (tibialis anterior) were realized. Biochemical markers were determined and an intestinal absorption test of D-glucose was performed. All extracts (100 mg/kg/day, p.o.) significantly (p<0.001) reduced blood glucose level at the 28th day of treatment with a more pronounced effect for methanolic extract. The treatments were well tolerated and induced a restoration of T-CHOL and HDL-C levels compared to the control group. Methanolic extract reduced the AIP (atherogenic index of plasma) by 45%. Histopathological analyzes of the pancreas showed regeneration of islets of Langerhans. Methanolic extract was the most effective in preventing intestinal glucose uptake up to 60.90% in relation to metformin. These results justify the use of this plant in traditional medicine against type 2 diabetes. However, other complementary studies should be done to identify the molecules responsible for this activity and their signaling voice.

Long‐term exposure to particulate matter (PM) pollution may directly increase the risk of developing tuberculosis (TB). Despite the known link, the multi–scale spatiotemporal variations in the burden of TB attributable to long‐term PM exposure remain largely unclear in China. In this study, we conducted a nationwide, multi‐scale risk assessment of the burden of TB attributable to long‐term PM2.5, PM2.5–10, and PM10 exposure from 2013 to 2019, employing the multivariate distributed lag nonlinear model (MVDLNM), Lorenz curve and Gini index. Our health impact assessments indicate that PM exposure has resulted in significant increases in TB burden. Specifically, approximately$1,202 million (95% CI: 801–1,573 million), $ 486 million (95% CI: 398–572 million), and $944 million (95% CI: 767–1,115 million) of health economic costs could be attributed to long‐term exposure to PM2.5, PM2.5–10, and PM10, respectively. Although the overall the burden of TB attributable to PM exposure was significantly reduced from 2013 to 2019, regional inequalities have become more pronounced. The Gini index reveals a clear disparity in the burden of TB related to PM exposure across provincial, city, and county levels. These disparities are most pronounced at the county level (0.4914–0.6801), followed by the city level (0.4135–0.6382), and are least evident at the province level (0.3672–0.6078). Overall, the regional inequalities in the burden of TB are more pronounced at finer spatial scales. Our study highlights the health impacts of long‐term exposure to PM on the incidence of TB across different spatiotemporal scales, and the findings provide strong scientific evidence for pollution mitigation and efforts to reduce regional inequality. Plain Language Summary Ambient particulate matter (PM) pollution is a significant environmental risk factor contributing to the high tuberculosis (TB) burden in China. Although substantial improvements in air quality have been achieved in recent years, the impact of these improvements on TB incidence remains unclear, and regional exposure inequity has seldom been explored. This study systematically evaluates how regional disparities in health economic costs attributable to long‐term exposure to different sizes of PM (PM2.5, PM2.5–10, and PM10) vary over time and across spatial scales, including the macro‐scale (provincial level), meso‐scale (city level), and micro‐scale (county level). It found that long‐term PM exposure caused billions of dollars in TB‐related health costs, with PM2.5 being the largest contributor. While overall PM‐related TB burden decreased nationwide from 2013 to 2019, inequalities between regions grew, especially at finer scales like counties. Disparities in TB burden were highest at the county level, demonstrating that local conditions strongly influence health risks. This study highlights the urgent need for targeted air quality and health policies in high‐risk areas to reduce TB burden and address health inequalities. Key Points Long‐term exposure to PM2.5–10 was associated with an increased risk of tuberculosis incidence Health economic losses attributable to long‐term particulate matter exposure exceeded one billion USD from 2013 to 2019 Regional inequalities in the tuberculosis burden were more pronounced at finer spatial scales

Bowen Zheng,1,2 Jun Zheng,1,2 Rucheng Yao1,21Department of Hepatopancreatobilary Surgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, People’s Republic of China; 2Yichang Central People’s Hospital, Yichang, Hubei, People’s Republic of ChinaCorrespondence: Jun Zheng; Rucheng Yao, Email [email protected]; [email protected]View the original paper by Dr Niyonkuru and colleagues

Background The tumor microenvironment in colorectal cancer (CRC) significantly influences disease progression and immune responses, particularly the role of macrophages in regulating immune evasion requires further investigation. Methods This study integrated data from the TCGA-COAD dataset with the GEO database, along with single-cell RNA sequencing data, to systematically analyze key genes in colorectal cancer. R software was utilized for data normalization and differential analysis, with criteria set at ∣log2FoldChange ∣ > 1 and adjusted p-value < 0.05 for gene selection. The Seurat package was employed for clustering single-cell data, while the “Monocle2” algorithm was used to perform pseudo-time analysis on the differentiation trajectory of macrophages. Additionally, non-negative matrix factorization (NMF) was applied for subtype classification of CRC patients, and various machine learning algorithms (such as LASSO and random forest models) were utilized to identify key pathogenic genes. Finally, PCR was employed to validate the expression of these key genes, and immune analysis software was used to assess their impact on immune cells, alongside pathway enrichment analysis. Results Through the integration of multi-omics data, we identified significant differential expression of VSIG4, CYBBC3AR1, and FCGR1A in CRC patients. LASSO and random forest models selected these three genes as critical pathogenic factors for CRC, with AUC values exceeding 0.8 across multiple machine learning models, demonstrating their high diagnostic efficacy. PCR validation further supported the differential expression of VSIG4 and other genes in CRC. Single-cell transcriptomic analysis revealed that VSIG4 was highly enriched in specific macrophage subpopulations and significantly influenced the tumor microenvironment by regulating CD8 + T cell immune exhaustion. Pseudo-time analysis indicated that the differentiation trajectory of macrophages during tumor progression was closely associated with VSIG4 expression. Additionally, cell communication analysis. highlighted the important role of VSIG4 in the interactions between macrophages and endothelial cells. Pathway enrichment analysis demonstrated that VSIG4 expression was closely linked to the regulation of the JAK-STAT pathway and metabolic pathways such as the TCA cycle. Conclusion This study provides the first evidence that VSIG4, CYBBC3AR1, and FCGR1A play critical roles in the immune microenvironment of colorectal cancer, particularly emphasizing the immunoregulatory function of VSIG4 in macrophage activity and CD8 + T cell immune exhaustion. PCR validation further confirmed the differential expression of these genes. These findings offer new insights into the molecular mechanisms of CRC and provide a potential theoretical basis for targeting VSIG4 in immunotherapy.