Search

Bacteria-mediated antitumor therapy has gained widespread attention for its innate tumor-targeting capability and excellent immune activation properties. Nevertheless, the clinical approval of bacterial therapies remains elusive primarily due to the formidable challenge of balancing safety with enhancing in vivo efficacy. In this study, leveraging the probiotic Escherichia coli Nissle1917 (EcN) emerges as a promising approach for colon cancer therapy, offering a high level of safety attributed to its lack of virulence factors and its tumor-targeting potential owing to its obligate anaerobic nature. Specifically, we delineate the erythrocyte (RBC) membrane-camouflaged EcN, termed as Trojan horse EcN@RBC, which triggers apoptosis in tumor cells by mitigating mitochondrial membrane potential (MMP) and subsequently activating the PINK1/Parkin pathway associated with mitophagy. Concurrently, the decline in MMP induced by mitophagy disrupts the mitochondrial permeability transition pore (MPTP), leading to the release of Cytochrome C and subsequent apoptosis induction. Moreover, synergistic effects were observed through the combination of the autophagy activator rapamycin, bolstering the antitumor efficacy in vivo. These findings offer novel insights into probiotic-mediated antitumor mechanisms and underscore the therapeutic potential of EcN@RBC for colon cancer patients.

Abstract Background Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. Results Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. Conclusion It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.

Many variations of the multiple zeta values have been found to play important roles in different branches of mathematics and theoretical physics in recent years, such as the cyclotomic/color version, which appears prominently in the computation of Feynman integrals. In this paper, we introduce a trigonometric variant of the Kaneko–Tsumura ψ-function (called the Kaneko–Tsumura ψ˜-function) and discover some nice properties similar to those for ordinary Kaneko–Tsumura ψ-values using the method of iterated integrals, which was first studied systematically by K.T. Chen in the 1960s. In particular, we establish some duality formulas involving the Kaneko–Tsumura ψ˜-function and alternating multiple T-values by adapting Yamamoto’s graphical representation method for computing special types of iterated integrals.

This paper presents an approach to summing a few families of infinite series involving hyperbolic functions, some of which were first studied by Ramanujan. The key idea is based on their contour integral representations and residue computations with the help of some well-known results of Eisenstein series given by Ramanujan, Berndt, et al. As our main results, several series involving hyperbolic functions are evaluated and expressed in terms of z=F12(1/2,1/2;1;x) and z′=dz/dx. When a certain parameter in these series is equal to π, the series are expressed in closed forms in terms of some special values of the Gamma function. Moreover, many new illustrative examples are presented.

Biodiversity plays a crucial role in the global ecosystem and is essential for the sustainable development of human society. Constructing scientifically ecological networks is the foundation of biodiversity conservation. While previous studies have focused on constructing urban ecological networks with an emphasis on ecological security and habitat quality, there remains a need for methods that align with biodiversity and conservation objectives at the urban agglomeration scale. In light of future climatic and environmental changes and the rapid pace of urbanization, this study focuses on the Beijing–Tianjin–Hebei urban agglomeration, a leading urban cluster in China. This study explores the development of ecological networks at the scale of urban agglomerations through the forecasting of bird species distributions with different migration habits, a critical indicator of biodiversity. The identification of ecological sources utilized 3 methodologies: morphological spatial pattern analysis, habitat quality assessment, and species distribution forecasting, together pinpointing 134 pivotal ecological sources. Utilizing circuit theory, the research delineates 117 primary ecological corridors, 285 secondary corridors, 9 potential ecological corridors, and 1,134 ecological nodes. By conducting a comprehensive analysis of the current state and spatial distribution patterns of various ecological network components, the study proposes specific implementation strategies. The findings offer vital spatial guidance for the planning of future urban conglomerates and the formulation of corresponding policies, thereby facilitating national ecological protection and restoration initiatives.

Peroxiredoxins (Prxs) widely exist in organisms and can prevent oxidative damage. Here, the characterization and biological function of NdPrx3 from Neocaridina denticulata sinensis were analyzed. The coding sequence of NdPrx3 consists of 684 bp open reading frame (ORF), encoding 227 amino acids with a predicted molecular weight of 24.7 kDa and theoretical pI 6.49. Multiple sequence alignments showed that the conserved domains of NdPrx3, including catalytic triad, dimer interface, decamer interface, peroxidatic, and resolving cysteines, were similar to those of other organisms. The phylogenetic relationship demonstrated that NdPrx3 clustered in the Prx3 class. The highest relative expression of NdPrx3 mRNA was confirmed in gill among the nine tissues from healthy shrimp. The transcript level of NdPrx3 was significantly upregulated from 0 h to 48 h and decreased in 72 h under copper challenge, indicating that NdPrx3 may play an important role in the copper challenge of N. denticulata sinensis. In addition, NdPrx3 was recombinantly expressed in E. coli and purified to one band on SDS-PAGE. The DNA protection of rNdPrx3 was verified. The enzymatic assay of the recombinant NdPrx3 indicated that it had the oxidoreductase function and was stable at a low temperature (10–30 °C).

Abstract The balance winding of the transformer is a compact and flexible technique for the common‐mode (CM) noise reduction of isolated power converters. A proper design of the grounding and turn number of the balance winding will generate an inverse displacement current to balance the CM noise flowing through the transformer. However, a trial and error process to find the optimum design is necessary for practical applications due to the unexplored source of calculation errors. In this paper, a quantitative analysis method of CM currents flowing through all the paths between windings is proposed for error quantifications. Based on an interleaved transformer, the capacitances are extracted with the help of electric field simulations, and the contribution of each path to the CM noise is analysed. Although the paths between adjacent layers are dominant in the CM noise, it is proved that ignoring non‐adjacent inter‐layer paths will lead to calculation errors due to the high voltage difference even with low capacitances. As both the application and verification of the proposed quantitative analysis method, the accurate evaluation of noise reduction effects and determination of the optimum balance winding turns can be achieved in experiments.

The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new “valve-off” starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R•), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R• facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic in vivo and in vitro results suggested that this radical-enhanced “valve-off” strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.

With the ongoing advancement of globalization significantly impacting the ecological environment, the continuous rise in the Land Surface Temperature (LST) is increasingly jeopardizing human production and living conditions. This study aims to investigate the seasonal variations in the LST and its driving factors using mathematical models. Taking the Wuhan Urban Agglomeration (WHUA) as a case study, it explores the seasonal characteristics of the LST and employs Principal Component Analysis (PCA) to categorize the driving factors. Additionally, it compares traditional models with machine-learning models to select the optimal model for this investigation. The main conclusions are as follows. (1) The WHUA’s LST exhibits significant differences among seasons and demonstrates distinct spatial-clustering characteristics in different seasons. (2) Compared to traditional geographic spatial models, Extreme Gradient Boosting (XGBoost) shows better explanatory power in investigating the driving effects of the LST. (3) Human Activity (HA) dominates the influence throughout the year and shows a significant positive correlation with the LST; Physical Geography (PG) exhibits a negative correlation with the LST; Climate and Weather (CW) show a similar variation to the PG, peaking in the transition; and the Landscape Pattern (LP) shows a weak positive correlation with the LST, peaking in winter while being relatively inconspicuous in summer and the transition. Finally, through comparative analysis of multiple driving factors and models, this study constructs a framework for exploring the seasonal features and driving factors of the LST, aiming to provide references and guidance for the development of the WHUA and similar regions.

Abstract Background Hemorrhage shock (HS) is characterized by decreased tissue oxygenation and organ damage due to severe blood loss. Protein tyrosine phosphatase receptor type O (PTPRO) is abnormally up-regulated in the rat lungs after trauma/HS. Methods To elucidate the regulatory mechanism of PTPRO in lung inflammation following HS, we established a rat model of HS via withdrawing blood by a catheter inserted into the femoral artery followed by resuscitation. The rats were infected with lentivirus harboring short hairpin RNA (shRNA) targeting PTPRO by intratracheal instillation. Results PTPRO was significantly up-regulated in rat lungs after HS. PTPRO knockdown enhanced epithelial integrity and reduced capillary leakage by up-regulating tight junction proteins zonula occludens-1 (ZO-1) and occludin (OCC) in the lungs. Besides, HS-induced myeloperoxidase activity and inflammatory cell infiltration was mitigated by PTPRO knockdown. The expression of inflammatory cytokines/chemokines (TNF-α, IL-6, MIP-2, MCP-1, and KC) in the lungs and bronchoalveolar lavage fluid was regressed after PTPRO knockdown. The nuclear factor kappa B (NF-κB) pathway was involved in HS-induced lung inflammation. PTPRO down-regulation inhibited the NF-κB pathway activation by suppressing the phosphorylation of NF-κB and its translocation from the cytoplasm into the nucleus in HS. Conclusion Taken together, we demonstrated that PTPRO knockdown may contribute to attenuating inflammation in HS-induced lung injury via inhibiting NF-κB pathway activation.

Legal information extraction requires identifying and classifying legal elements from specific legal documents. Considering that information extraction is mainly regarded as the first step in natural language understanding, the quality of legal information extraction results certainly has an immense impact on the performance of various legal artificial intelligence (AI) downstream tasks. However, Chinese judicial information extraction datasets are very scarce due to the particularity of legal documents. In response to this situation, we constructed a dataset for Challenge of AI in Law - Information Extraction V1.0 (CAILIE 1.0). The following two features of CAILIE are worth highlighting: 1) the entity definition focuses on more fine-grained theft document information, providing more interpretability for downstream legal AI; and 2) we define entity labels with judicial attributes based on natural attribute labels to meet the needs of Chinese judicial practice. We implement some classic models on this dataset. The experimental results show that legal information extraction is still challenging and additional research is required for this task to be solved.

Plant residue decomposition can significantly affect the water environment of wetland ecosystems. However, little is known about the trajectory and the key drivers of the different initial mass of residue (IMR) that regulate water quality. Here, we conducted a study of 210 days with an in situ experiment to examine the impact of the change in IMR and the key decomposition parameters of Phragmites australis on the water quality in the growing season of 2019 in Baiyangdian wetland in North China. Five IMR of the Phragmites were applied, ranging from 0 to 1000 g with 250 g increments. The chemical oxygen demand (COD_W), total organic carbon (TOC_W), total nitrogen (TN_W) and total phosphorus (TP_W) of the water, and the total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), cellulose, lignin, decomposition rate (k) and the remaining mass of the Phragmites in the bag (RM) were monitored. Our results showed that the IMR of the Phragmites only marginally influenced the decomposition of itself and; the variations in the level of the water indicators were ranked as TN > TP > COD > TOC and; the impacts of IMR were longer on TOC and COD than on TP and TN and; the change in water quality was significantly influenced by the Phragmites decomposition and highly correlated with the change in TOC, cellulose and k of decomposing Phragmites residue. These results indicated that the impact of 250 g of IMR on the water was negligible after 120 days, suggesting that the optimal harvest rate of the Phragmites should be above 75% in the Baiyangdian wetland, despite the strong impact at the beginning and; the impact of change in IMR on water quality can be explained by the change in the decomposition parameters of the decomposing Phragmites residue, where such a decomposition-based explanation might be a promising tool to link wetland plant management and water quality.

Abstract Background Astrocyte over-activation and extensive neuron loss are the main characteristic pathological features of spinal cord ischemia–reperfusion injury (SCII). Prior studies have placed substantial emphasis on the role of heat shock protein family A member 8 (HSPA8) on postischemic myocardial inflammation and cardiac dysfunction. However, it has never been determined whether HSPA8 participates in astrocyte activation and thus mediated neuroinflammation associated with SCII. Methods The left renal artery ligation-induced SCII rat models and oxygen–glucose deprivation and reoxygenation (OGD/R)-induced rat primary cultured astrocytes were established. The lentiviral vector encoding short hairpin RNA targeting HSPA8 was delivered to the spinal cord by intrathecal administration or to culture astrocytes. Then, the spinal neuron survival, gliosis, and nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and its related pro-inflammatory cytokines were analyzed. Results SCII significantly enhanced the GFAP and HSPA8 expression in the spinal cord, resulting in blood–brain barrier breakdown and the dramatical loss of spinal neuron and motor function. Moreover, injury also increased spinal nuclear factor-kappa B (NF-κB) p65 phosphorylation, NLRP3 inflammasome-mediated caspase-1 activation, and subsequent interleukin (IL)-1β as well as IL-18 secretion. Silencing the HSPA8 expression efficiently ameliorated the spinal cord tissue damage and promoted motor function recovery after SCII, through blockade of the astrocyte activation and levels of phosphorylated NF-κB, NLRP3, caspase-1, IL-1β, and IL-18. Further in vitro studies confirmed that HSPA8 knockdown protected astrocytes from OGD/R-induced injury via the blockade of NF-κB and NLRP3 inflammasome activation. Conclusion Our findings indicate that knockdown of HSPA8 inhibits spinal astrocytic damage after SCII, which may provide a promising therapeutic strategy for SCII treatment.

Brainstem gliomas are heterogenous in terms of clinical outcome and disease etiology. Here, the authors present a genetic and epigenetic landscape of brainstem gliomas, finding distinct epigenetic clusters associated with unique genetic and clinical profiles.

Food safety issues were a growing concern in most countries; affecting the people’s health, social stability, economic development, and dairy product safety had always been an important topic of concern for consumers. This study is aimed at investigating the concerns of consumers about dairy product label information and its influencing factors. These survey data were reported for 4408 respondents with a total response rate of 96.35%. Findings revealed that consumers’ concern on dairy product label information was relatively high on the whole, and there were significant differences in the level of consumers’ concern on dairy product label information (P

This paper presents a real-time path planning approach for controlling the motion of space-based robots. The algorithm can plan three-dimensional trajectories for agents in a complex environment which includes numerous static and dynamic obstacles, path constraints, and/or performance constraints. This approach is extended based on the dynamic window approach (DWA). As the classic reactive method for obstacle avoidance, DWA uses an optimized function to select the best motion command. The original DWA optimization function consists of three weight terms. Changing the weights of these terms will change the behavior of the algorithm. In this paper, to improve the evaluation ability of the optimization function and the robot’s ability to adapt to the environment, a new optimization function is designed and combined with fuzzy logic to adjust the weights of each parameter of the optimization function. Given that DWA has the defect of local minima, which makes the robot hard to escape U-shaped obstacles, a dual dynamic window method and local goals are adopted in this article to help the robot escape local minima. By comparison, the proposed method is superior to traditional DWA and fuzzy DWA (F_DWA) in terms of computational efficiency, smoothness and security.

As an important piece of equipment in industrial production, the health of an air compressor directly impacts the success of production. Therefore, researching fault diagnosis methods for air compressors is of significant importance in improving the continuity, reliability, and safety of production. Traditional fault diagnosis methods, however, struggle to obtain accurate fault features. The measurement of feature distribution differences between various working conditions lacks sufficient domain adaptability, making it challenging to achieve high recognition accuracy. Additionally, the operation of air compressors generates background noise, which can introduce interference and impact the accuracy in fault detection. In order to overcome these limitations, a fault diagnosis method for air compressors based on feature fusion is proposed. Firstly, the Mel-frequency cepstral coefficients (MFCC) features and wavelet transform features of the air compressor are extracted separately. Then, late fusion is applied at the decision level to combine confidence scores and predicted bounding boxes. The best network model is determined based on evaluation metrics to complete the classification. Based on the experimental results analysis, the feature fusion method demonstrated superior recognition performance. [ABSTRACT FROM AUTHOR]

A comprehensive assessment of climate change vulnerability is imperative for formulating effective adaptation strategies and advancing sustainable development goals. As one of the most climate-vulnerable regions globally, the Pan-Third Pole area lacks transnational vulnerability assessments, which poses a significant obstacle to efficient climate adaptation. This study conducted transnational comparisons based on primary micro-survey data collected uniformly across Nepal, Cambodia, Thailand, and Myanmar, which are all located in the Pan-Third Pole region. Evaluating and comparing the vulnerabilities employed an extended framework of climate change indicators. The findings reveal substantial variations in vulnerability among the countries, with Cambodia exhibiting the highest vulnerability, followed by Thailand, Myanmar, and Nepal in descending order, primarily due to differences in exposure. Household exposure to climate change also varied significantly. Sensitivity scores decreased in the order of Nepal > Cambodia > Thailand > Myanmar, with demographic factors, tap water accessibility, and land being the major contributors and sources of differentiation among the countries. Regarding adaptability, Thailand demonstrated the highest adaptability, with human and financial capital as the key differentiators. The outcomes underscore the need for tailored policy measures addressing the diverse vulnerabilities, including enhancing household disaster prevention and capital protection. Furthermore, targeted international investments are crucial for improving adaptability among smallholders in this unique region. [ABSTRACT FROM AUTHOR]