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Land-use change exerts a profound influence on ecosystem services (ES), and accurately assessing its spatiotemporal dynamics is essential for achieving regional sustainability. Taking Shandong Province as a case study, this research integrates the PLUS and InVEST models to simulate the impacts of land-use changes on carbon storage and habitat quality in Shandong Province between 2000 and 2020, and to project their dynamics under different scenarios for 2030. The InVEST (Integrated Valuation of Ecosystem Services and Tradeoffs) model was employed to reassess variations in carbon storage (CS) and habitat quality (HQ). The main findings are as follows: (1) Cultivated land decreased by 12.3%, while construction land expanded by 51.04%, predominantly replacing farmland and forested areas, resulting in a distinct spatial pattern characterized by an “urbanized east and agricultural west.” (2) Carbon storage declined by approximately 63 million tons, primarily due to urban expansion. (3) Habitat quality experienced a 3.6% decrease, with significant ecological fragmentation identified in the central mountainous regions and the Yellow River Delta, driven by intensified urbanization and agricultural activities. (4) Future scenario simulations indicate that under the ecological conservation scenario, carbon storage could increase by 12.5% and habitat quality could reach 0.572 by 2040; in contrast, the natural development scenario suggests ongoing degradation. These findings highlight the trade-offs between land development and ecosystem services, emphasizing the necessity of reinforcing ecological zoning, compensation mechanisms, and the establishment of ecological corridors. This study provides a scientific basis for advancing sustainable land-use planning and ecosystem management.

Engineering microbial consortia to express complex biosynthetic pathways efficiently for the production of valuable compounds is a promising approach for metabolic engineering and synthetic biology. Here, we report the design, optimization, and scale-up of an Escherichia coli - E. coli coculture that successfully overcomes fundamental microbial production limitations, such as high-level intermediate secretion and low-efficiency sugar mixture utilization. For the production of the important chemical cis , cis -muconic acid, we show that the coculture approach achieves a production yield of 0.35 g/g from a glucose/xylose mixture, which is significantly higher than reported in previous reports. By efficiently producing another compound, 4-hydroxybenzoic acid, we also demonstrate that the approach is generally applicable for biosynthesis of other important industrial products.

Traditionally, lactate has been considered a ‘waste product’ of cellular metabolism. Recent findings have shown that lactate is a substance that plays an indispensable role in various physiological cellular functions and contributes to energy metabolism and signal transduction during immune and inflammatory responses. The discovery of lactylation further revealed the role of lactate in regulating inflammatory processes. In this review, we comprehensively summarize the paradoxical characteristics of lactate metabolism in the inflammatory microenvironment and highlight the pivotal roles of lactate homeostasis, the lactate shuttle, and lactylation (‘lactate clock’) in acute and chronic inflammatory responses from a molecular perspective. We especially focused on lactate and lactate receptors with either proinflammatory or anti-inflammatory effects on complex molecular biological signalling pathways and investigated the dynamic changes in inflammatory immune cells in the lactate-related inflammatory microenvironment. Moreover, we reviewed progress on the use of lactate as a therapeutic target for regulating the inflammatory response, which may provide a new perspective for treating inflammation-related diseases.

The clinical application of conventional doxorubicin (CDOX) was constrained by its side effects. Liposomal doxorubicin was developed to mitigate these limitations, showing improved toxicity profiles. However, the adverse events associated with liposomal doxorubicin and CDOX have not yet been comprehensively evaluated in clinical settings. The FAERS data from January 2004 to December 2022 were collected to analyze the adverse events of liposomal doxorubicin and CDOX. Disproportionate analysis and Bayesian analysis were employed to quantify this association. Our analysis incorporated 68,803 adverse event reports related to Doxil/Caelyx, Myocet and CDOX. The relative odds ratios (RORs, 95%CI) for febrile neutropenia associated with CDOX, Doxil/Caelyx, and Myocet were 42.45 (41.44; 43.48), 17.53 (16.02; 19.20), and 34.68 (26.63; 45.15) respectively. For cardiotoxicity, they were 38.87(36.41;41.49), 17.96 (14.10; 22.86), and 37.36 (19.34; 72.17). For Palmar-Plantar Erythrodysesthesia (PPE), the RORs were 6.16 (5.69; 6.68), 36.13 (32.60; 40.06), and 19.69 (11.59; 33.44). Regarding onset time, significant differences adverse events including neutropenia, PPE, pneumonia and malignant neoplasm progression. This study indicates that clinical monitoring for symptoms of cardiotoxicity of CDOX and Myocet, and PPE and interstitial lung disease of Doxil should be performed. Additionally, the onset time of febrile neutropenia, malignant neoplasm progression, and pneumonia associated with Doxil and Myocet merits particular attention. Continuous surveillance, risk evaluations, and additional comparative studies between liposomal doxorubicin and CDOX were recommended.

Background cis , cis -Muconic acid is an important chemical that can be biosynthesized from simple substrates in engineered microorganisms. Recently, it has been shown that engineering microbial cocultures is an emerging and promising approach for biochemical production. In this study, we aim to explore the potential of the E. coli – E. coli coculture system to use a single renewable carbon source, glycerol, for the production of value-added product cis , cis -muconic acid. Results Two coculture engineering strategies were investigated. In the first strategy, an E. coli strain containing the complete biosynthesis pathway was co-cultivated with another E. coli strain containing only a heterologous intermediate-to-product biosynthetic pathway. In the second strategy, the upstream and downstream pathways were accommodated in two separate E. coli strains, each of which was dedicated to one portion of the biosynthesis process. Compared with the monoculture approach, both coculture engineering strategies improved the production significantly. Using a batch bioreactor, the engineered coculture achieved a 2 g/L muconic acid production with a yield of 0.1 g/g. Conclusions Our results demonstrate that coculture engineering is a viable option for producing muconic acid from glycerol. Moreover, microbial coculture systems are shown to have the potential for converting single carbon source to value-added products.

The mechanism of action of artemisinin and its derivatives, the most potent of the anti-malarial drugs, is not completely understood. Here we present an unbiased chemical proteomics analysis to directly explore this mechanism in Plasmodium falciparum . We use an alkyne-tagged artemisinin analogue coupled with biotin to identify 124 artemisinin covalent binding protein targets, many of which are involved in the essential biological processes of the parasite. Such a broad targeting spectrum disrupts the biochemical landscape of the parasite and causes its death. Furthermore, using alkyne-tagged artemisinin coupled with a fluorescent dye to monitor protein binding, we show that haem, rather than free ferrous iron, is predominantly responsible for artemisinin activation. The haem derives primarily from the parasite’s haem biosynthesis pathway at the early ring stage and from haemoglobin digestion at the latter stages. Our results support a unifying model to explain the action and specificity of artemisinin in parasite killing. The mechanism of action of artemisinin, an antimalarial drug, is not well understood. Here, the authors use a labelled artemisinin analogue to show that the drug is mainly activated by haem and then binds covalently to over 120 proteins in the malaria parasite, affecting many of its cellular processes.

Researchers have investigated the potential of leveraging pre-trained language models, such as CodeBERT, to enhance source code-related tasks. Previous methodologies have relied on CodeBERT’s ‘[CLS]’ token as the embedding representation of input sequences for task performance, necessitating additional neural network layers to enhance feature representation, which in turn increases computational expenses. These approaches have also failed to fully leverage the comprehensive knowledge inherent within the source code and its associated text, potentially limiting classification efficacy. We propose CodeClassPrompt, a text classification technique that harnesses prompt learning to extract rich knowledge associated with input sequences from pre-trained models, thereby eliminating the need for additional layers and lowering computational costs. By applying an attention mechanism, we synthesize multi-layered knowledge into task-specific features, enhancing classification accuracy. Our comprehensive experimentation across four distinct source code-related tasks reveals that CodeClassPrompt achieves competitive performance while significantly reducing computational overhead.

Objectives To comprehend the relationship between various indicators of health service equity and patients’ health expenditure poverty in different regions of China, identify areas where equity in health service is lacking and provide ideas for improving patients’ health expenditure poverty. Method Data from China Family Panel Studies (CFPS) in 2018 and the HFGT index formula were used to calculate the health expenditure poverty index of each province. Moreover, Global Moran’s I and Local Moran’s I test are applied to measure whether there is spatial aggregation of health expenditure poverty. Finally, an elastic net regression model is established to analyze the impact of health service equity on health expenditure poverty, with the breadth of health expenditure poverty as the dependent variable and health service equity as the independent variable. Results In the developed eastern provinces of China, the breadth of health expenditure poverty is relatively low. There is a significant positive spatial agglomeration. “Primary medical and health institutions per 1,000 population”, “rural doctors and health workers per 1,000 population”, “beds in primary medical institutions per 1,000 population”, “proportion of government health expenditure” and “number of times to participate in medical insurance (be aided) per 1,000 population” have a positive impact on health expenditure poverty. “Number of health examinations per capita” and “total health expenditure per capita” have a negative impact on health expenditure poverty. Both effects passed the significance test. Conclusion To enhance the fairness of health resource allocation in China and to alleviate health expenditure poverty, China should rationally plan the allocation of health resources at the grassroots level, strengthen the implementation of hierarchical diagnosis and treatment and encourage the investment in business medical insurance industry. Meanwhile, it is necessary to increase the intensity of medical assistance and enrich financing methods. All medical expenses of the poorest should be covered by the government.

Pancreatic ductal adenocarcinoma (PDAC) is a common malignant tumor of the digestive tract. Although gemcitabine and other therapeutic agents are effective in patients with advanced and metastatic pancreatic cancer, drug resistance has severely limited their use. However, the mechanisms of gemcitabine resistance in pancreatic cancer are poorly understood. In this study, ATAC-seq, ChIP-seq, and RNA-seq were performed to compare chromatin accessibility and gene expression in a patient-derived tumor xenograft (PDX) model of pancreatic cancer with or without gemcitabine resistance. Analyzing these sequencing data, we found a dramatic change in chromatin accessibility in the PDX model of gemcitabine-resistant tissues and identified a key gene, UBR7, which plays an important role in mediating gemcitabine resistance. Further research found that depletion of UBR7 significantly increased pancreatic carcinogenesis and the immunosuppressive microenvironment. Mechanistically, depleted UBR7 increased the stability of PRMT5, thereby promoting glycolysis in pancreatic cancer cells. Finally, an inhibitor that blocks PRMT5 (DS-437) significantly reduced gemcitabine resistance in pancreatic cancer caused by UBR7 depletion. In conclusion, our results illustrate that the UBR7-PRMT5 axis is a key metabolic regulator of PDAC and a promising target for the clinical treatment of gemcitabine resistance in PDAC.

Background Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, showing aggressive clinical behaviors and poor outcomes. It urgently needs new therapeutic strategies to improve the prognosis of TNBC. Bioinformatics analyses have been widely used to identify potential biomarkers for facilitating TNBC diagnosis and management. Methods We identified potential biomarkers and analyzed their diagnostic and prognostic values using bioinformatics approaches. Including differential expression gene (DEG) analysis, Receiver Operating Characteristic (ROC) curve analysis, functional enrichment analysis, Protein-Protein Interaction (PPI) network construction, survival analysis, multivariate Cox regression analysis, and Non-negative Matrix Factorization (NMF). Results A total of 105 DEGs were identified between TNBC and other breast cancer subtypes, which were regarded as heterogeneous-related genes. Subsequently, the KEGG enrichment analysis showed that these genes were significantly enriched in ‘cell cycle’ and ‘oocyte meiosis’ related pathways. Four (FAM83B, KITLG, CFD and RBM24) of 105 genes were identified as prognostic signatures in the disease-free interval (DFI) of TNBC patients, as for progression-free interval (PFI), five genes (FAM83B, EXO1, S100B, TYMS and CFD) were obtained. Time-dependent ROC analysis indicated that the multivariate Cox regression models, which were constructed based on these genes, had great predictive performances. Finally, the survival analysis of TNBC subtypes (mesenchymal stem-like [MSL] and mesenchymal [MES]) suggested that FAM83B significantly affected the prognosis of patients. Conclusions The multivariate Cox regression models constructed from four heterogeneous-related genes (FAM83B, KITLG, RBM24 and S100B) showed great prediction performance for TNBC patients’ prognostic. Moreover, FAM83B was an important prognostic feature in several TNBC subtypes (MSL and MES). Our findings provided new biomarkers to facilitate the targeted therapies of TNBC and TNBC subtypes.