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Methamphetamine (METH) use disorder (MUD) is characterized by compulsive drug-seeking behavior and substantial neurotoxicity, posing a considerable burden on individuals and society. Traditionally perceived as a localized central nervous system disorder, recent preclinical and clinical studies have elucidated that MUD is a multifaceted disorder influenced by various biological systems, particularly the immune system. Emerging evidence suggests that both central and peripheral immune responses play a crucial role in the initiation and persistence of MUD. Conceptualizing it as a systemic immune process prompts significant inquiries regarding the mechanisms of communication between peripheral and central compartments. Also, whether this intercommunication could serve as diagnostic biomarkers or therapeutic targets. This review begins by offering an overview of mechanistic studies pertaining to the neuroimmune and peripheral immune systems. Finally, future directions are suggested through the integration of innovative technologies and multidimensional data to promote the translation of basic mechanistic research into clinical diagnostic and therapeutic interventions.

Metabolic labeling of the cell surface with a caged azide sugar enabled cleavage-mediated activation by enzymes overexpressed in cancer cells, allowing enhanced targeted delivery of a doxorubicin conjugate through copper-free click chemistry. Distinguishing cancer cells from normal cells through surface receptors is vital for cancer diagnosis and targeted therapy. Metabolic glycoengineering of unnatural sugars provides a powerful tool to manually introduce chemical receptors onto the cell surface; however, cancer-selective labeling still remains a great challenge. Herein we report the design of sugars that can selectively label cancer cells both in vitro and in vivo . Specifically, we inhibit the cell-labeling activity of tetraacetyl- N -azidoacetylmannosamine (Ac 4 ManAz) by converting its anomeric acetyl group to a caged ether bond that can be selectively cleaved by cancer-overexpressed enzymes and thus enables the overexpression of azido groups on the surface of cancer cells. Histone deacetylase and cathepsin L-responsive acetylated azidomannosamine, one such enzymatically activatable Ac 4 ManAz analog developed, mediated cancer-selective labeling in vivo , which enhanced tumor accumulation of a dibenzocyclooctyne–doxorubicin conjugate via click chemistry and enabled targeted therapy against LS174T colon cancer, MDA-MB-231 triple-negative breast cancer and 4T1 metastatic breast cancer in mice.

Different from conventional single-task optimization, the recently proposed multitasking optimization (MTO) simultaneously deals with multiple optimization tasks with different types of decision variables. MTO explores the underlying similarity and complementarity among the component tasks to improve the optimization process. The well-known multifactorial evolutionary algorithm (MFEA) has been successfully introduced to solve MTO problems based on transfer learning. However, it uses a simple and random inter-task transfer learning strategy, thereby resulting in slow convergence. To deal with this issue, this paper presents a two-level transfer learning (TLTL) algorithm, in which the upper-level implements inter-task transfer learning via chromosome crossover and elite individual learning, and the lower-level introduces intra-task transfer learning based on information transfer of decision variables for an across-dimension optimization. The proposed algorithm fully uses the correlation and similarity among the component tasks to improve the efficiency and effectiveness of MTO. Experimental studies demonstrate the proposed algorithm has outstanding ability of global search and fast convergence rate.

Anthropogenic factors play an important role in shaping the distribution of wildlife species and their habitats, and understanding the influence of human activities on endangered species can be key to improving conservation efforts as well as the implementation of national strategies for sustainable development. Here, we used species distribution modeling to assess human impacts on the endangered red panda (Ailurus fulgens) in high‐altitude regions of Nepal. We found that the distance to paths (tracks used by people and animals), livestock density, human population density, and annual mean temperature were the most important factors determining the habitat suitability for red pandas in Nepal. This is the first study that attempts to use comprehensive environmental and anthropogenic variables to predict habitat suitability for the red pandas at a national level. The suitable habitat identified by this study is important and could serve as a baseline for the development of conservation strategies for the red panda in Nepal. The distance to paths, livestock density, human population density, and annual mean temperature were the most important factors determining the habitat suitability for red pandas in Nepal.

The Confucian hermeneutic approach to the Yijing 易經 (or Book of Changes) delineates a transition from the pursuit of divinatory meaning to the cultivation of virtue and action. As an integral part of the Yijing’s semantic framework, decisive phrases (Duanci 斷辭)—such as those denoting auspiciousness or ominousness—not only reflect historical efforts to ascertain the significance of divinatory cases, but also embody a distinct normative orientation inherent in the text’s teachings. This orientation not only guides human action but also shapes moral character, which in turn provides the foundation for virtuous and effective action. The interpretive paradigm initiated by Confucian exegetes thus offers valuable insights for contemporary theories of ethics and practical philosophy.

Colorectal cancer is one of the most common gastrointestinal cancers and the second leading cause of cancer-related death. Although colonoscopy screening has greatly improved the early diagnosis of colorectal cancer, its recurrence and metastasis are still significant problems. Tumour cells usually have the hallmark of metabolic reprogramming, while fatty acids play important roles in energy storage, cell membrane synthesis, and signal transduction. Many pathways of fatty acid metabolism (FAM) are involved in the occurrence and development of colon cancer, and the complex molecular interaction network contains a variety of genes encoding key enzymes and related products. Clinical information and RNA sequencing data were collected from TCGA and GEO databases. The prognosis model of colon cancer was constructed by LASSO-Cox regression analysis among the selected fatty acid metabolism genes with differential expression. Nomogram for the prognosis model was also constructed in order to analyze its value in evaluating the survival and clinical stage of the colon cancer patients. The differential expression of the selected genes was verified by qPCR and immunohistochemistry. GSEA and GSVA were used to analyze the enrichment pathways for high- and low-risk groups. CIBERSORT was used to analyze the immune microenvironment of colon cancer and to compare the infiltration of immune cells in the high- and low-risk groups. The \"circlize\" package was used to explore the correlation between the risk score signature and immunotherapy for colon cancer. We analysed the differential expression of 704 FAM-related genes between colon tumour and normal tissue and screened 10 genes with prognostic value. Subsequently, we constructed a prognostic model for colon cancer based on eight optimal FAM genes through LASSO Cox regression analysis in the TCGA-COAD dataset, and its practicality was validated in the GSE39582 dataset. Moreover, the risk score calculated based on the prognostic model was validated as an independent prognostic factor for colon cancer patients. We further constructed a nomogram composed of the risk score signature, age and American Joint Committee on Cancer (AJCC) stage for clinical application. The colon cancer cohort was divided into high- and low-risk groups according to the optimal cut-off value, and different enrichment pathways and immune microenvironments were depicted in the groups. Since the risk score signature was significantly correlated with the expression of immune checkpoint molecules, the prognostic model might be able to predict the immunotherapy response of colon cancer patients. In summary, our findings expand the prognostic value of FAM-related genes in colon cancer and provide evidence for their application in guiding immunotherapy.

Purpose To evaluate the effectiveness of intraoperative dexmedetomidine in preventing postoperative delirium (POD) in pediatric patients undergoing lower extremity orthopedic surgery. Methods This retrospective study included pediatric patients aged 3–12 years who underwent lower extremity orthopedic surgery and received single-shot caudal block combined with intravenous patient-controlled analgesia (IV-PCA) from January 2021 to December 2023. Patients were divided into two groups according to intraoperative adjuvant medication: dexmedetomidine (1 µg/kg) or sufentanil (0.1 µg/kg). Propensity score matching (PSM) was used to balance baseline characteristics. The primary outcome was the incidence of POD, assessed by the Pediatric Anesthesia Emergence Delirium (PAED) scale. Secondary outcomes included postoperative pain scores (r-FLACC scale) and adverse events. Results After PSM, 128 patients (64 pairs) were analyzed. The incidence of POD was significantly lower in the dexmedetomidine group compared to the sufentanil group (14.1% vs. 34.4%, p  = 0.01). Multivariate logistic regression revealed that intraoperative dexmedetomidine was independently associated with a reduced risk of POD (OR = 0.29, 95% CI: 0.12–0.74, p  < 0.01). Dexmedetomidine also resulted in lower r-FLACC pain scores in the PACU and during the first 6 h postoperatively (all p  < 0.01). No significant differences in hemodynamic changes or adverse events were observed between the groups. Conclusion Intraoperative dexmedetomidine significantly reduces the incidence of POD and improves early postoperative pain control in pediatric patients undergoing lower extremity orthopedic surgery, without increasing adverse events.

The rapid expansion of urban land has altered land use/land cover (LULC) types, affecting land surface temperatures (LSTs) and intensifying the urban heat island (UHI) effect, a prominent consequence of urbanization. This study, which focuses on Harbin, a representative city in a cold region, employs the patch-generating land use simulation (PLUS) model to predict LULC changes and a Bidirectional Long Short-Term Memory (Bi-LSTM) model to predict LST. The PLUS model exhibits a high prediction accuracy, evidenced by its FoM coefficient of 0.15. And the Bi-LSTM model also achieved high accuracy, with an R2 value of 0.995 and 0.950 and a root mean square error (RMSE) of 0.199 and 0.390 for predictions in winter and summer, respectively, surpassing existing methods. This study analyzed the trends in LULC, LST, and the urban thermal field variance index (UTFVI) to assess the relationships among LST, LULC, and UTFVI. The results show that urban land increased by 27.81%, and woodland and grassland decreased by 61.07% from 2005 to 2030. Areas with high temperatures increased by 40.86% in winter and 60.90% in summer. The proportion of the medium UTFVI zone (0.005–0.010) in urban land increased by 50.71%, and the proportion of areas with medium UTFVI values and above (>0.005) decreased at a rate of 84.70%. This finding suggests that the area affected by the UHI has decreased, while the UHI intensity in some regions has increased. This study provides a technical reference for future urban development and thermal environment management in cold regions.

Understanding the spatial morphological characteristics and driving factors of rural settlements in ethnic minority areas is crucial for the conservation and tourism development of ethnic villages. Accordingly, this study employs Shuanglang Town, China as a case study, adopting an integrated approach that combines spatial syntax analysis, the optimal parameter geodetector model, and GIS spatial analysis techniques. This comprehensive methodology systematically investigates the spatial morphological features, differentiation characteristics, and influencing factors of ethnic villages. The findings reveal the logical lineage and formation mechanisms underlying the overall layout, street network, and public spaces of the villages. Specifically, the results demonstrate (1) a discernible gradation in spatial configurations, transitioning from compact “back mountain villages” in the northeast to more dispersed “seaside villages” in the southwest, with notable disparities in accessibility among different villages; (2) topography, water distribution, and water quality as the dominant factors shaping village spatial patterns; (3) the interactive and heterogeneous effects of multiple natural and anthropogenic factors, including topography, water resources, agricultural practices, and ethnic cultural traditions, significantly influencing the spatial morphology of villages; and (4) common principles governing the site selection of different ethnic village typologies, reflecting the villagers’ understanding and intelligent utilization of the natural environment. This study contributes to comprehending the spatial characteristics of rural settlements in ethnic minority areas and provides a theoretical and practical foundation for advancing analogous rural revitalization initiatives. The findings offer insights into the spatial logic and formation processes of ethnic villages, informing conservation efforts and sustainable tourism development strategies.

Cell-cultured meat holds significant environmental value as an alternative protein source. Throughout the 21st century, cell-cultured meat has progressively penetrated commercial markets. However, a systematic review encompassing the entire field needs improvement. Employing Citespace, Vosviewer, and R-Bibliometrix software, a bibliometric analysis was used to present the research progress and general development trends of 484 articles on cell-cultured meat from 2000 to 2022 based on countries, authors, institutions, and keywords. This analysis provides ideas for the future development of cell-cultured meat in different countries or regions worldwide. Research on cell-cultured meat from 2000 to 2022 has undergone two phases: fluctuating growth (2000–2013) and rapid growth (2013–2022). Noteworthy contributions to cell-cultured meat studies emerge from author groups in the United States of America, the United Kingdom, and China, with influential institutions like the University of Bath significantly impacting pertinent research. Furthermore, over the past two decades, research has leaned towards exploring topics such as “biomaterials”, “cultured”, “land use”, “public opinion”, “animal welfare”, and “food safety”. Furthermore, this study reveals differences in nomenclature between regions and institutions. “Cultured meat” is more popular in some countries than in other forms. Institutions in Asia use “cultured meat” more frequently; however, institutions in the Americas adopt “cultivated meat” and rarely adopt “in vitro meat”, and institutions in the European region have no particularly prominent tendency towards a specific nomenclature. Future research should emphasize aligning the labeling of cell-cultured meat with effective management strategies and referencing regulatory policies across various countries. For the first time, we use three different bibliometric methods to analyze temporal and spatial variation in research on cellular meat. The results of this study have a multiplier effect. We provide a theoretical basis and a practical reference for the identification of alternatives in the dual context of “food crisis and food security” and “climate crisis”. At the same time, we also provide a reference for the sustainable development of the food system.