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Abstract Diabetic encephalopathy is a common complication of type 1 diabetes. However, there have been few studies on cognitive impairment and hippocampal damage in type 1 diabetes mellitus (T1DM) using dogs as experimental animals. To investigate the effects of diabetes on the CNS, 40 adult beagles were divided into streptozotocin/alloxan type 1 diabetes model and control groups. The duration of diabetes in the model group was 120 days. A cognitive dysfunction scale was used to assess cognitive function. Hematoxylin and eosin and Golgi-Cox staining methods were used to observe morphological damage to the hippocampus. Transcriptomics was used to investigate differential gene expression in the hippocampus. The results showed that the cognitive dysfunction score of the model group was significantly higher than that of the control group. In addition, the number of normal neurons, the complexity of dendritic morphology, and the density of dendritic spines were decreased in the hippocampus of diabetic dogs. A total of 672 differentially expressed genes (DEGs) were identified, 289 of which were upregulated, and 383 were downregulated. Modified genes included DBH, IGFBP2, AVPR1A, and DRAXIN. In conclusion, type 1 diabetic dogs exhibit cognitive dysfunction. The DEGs were mainly enriched in metabolic, PI3K-Akt signaling, and neuroactive ligand-receptor interaction pathways.

Copper (Cu) is one of the essential trace elements and is widespread in the environment. However, excessive exposure will induce toxicity in animals. To investigate the potential mechanisms of Cu-induced porcine spleen toxicity, sixty 30-day-old pigs were randomly divided into three groups. The control group was fed a basal diet and two treatment groups were separately fed the diet with 125 mg/kg and 250 mg/kg of Cu for 80 days. The result of immunohistochemical staining showed that the autophagy marker p62 was significantly increased under Cu exposure, and the immunofluorescence results showed the same trend as LC33-. Meanwhile, Cu intensified autophagy by increasing the expression levels of autophagy-related genes and proteins (LC3, p62, ATG5, Beclin1, and PINK1). These results suggested that long-term Cu exposure induced excessive autophagy in the porcine spleen, laying the groundwork for future studies on Cu-induced immunotoxicity in the spleen and increasing the public safety awareness of the excessive Cu-induced contamination in the environment.

Dear Editor, Males-absent-on-the-first （MOF, also called MYST1 or KAT8） is a histone acetyltransferase （HAT） belonging to the MOZ, Ybf2/Sas3, Sas2 and Tip60 （MYST） family. MOF has been shown to possess a specific HAT activity towards Lysl6 of histone H4 （H4K16） [1]. Homozygous knockout of MOF in mice results in loss of H4K16 acetylation and embryonic lethality,

In the Unmanned Aerial Vehicle (UAV) system, finding a flight planning path with low cost and fast search speed is an important problem. However, in the complex three-dimensional (3D) flight environment, the planning effect of many algorithms is not ideal. In order to improve its performance, this paper proposes a UAV path planning algorithm based on improved Harris Hawks Optimization (HHO). A 3D mission space model and a flight path cost function are first established to transform the path planning problem into a multidimensional function optimization problem. HHO is then improved for path planning, where the Cauchy mutation strategy and adaptive weight are introduced in the exploration process in order to increase the population diversity, expand the search space and improve the search ability. In addition, in order to reduce the possibility of falling into local extremum, the Sine-cosine Algorithm (SCA) is used and its oscillation characteristics are considered to gradually converge to the optimal solution. The simulation results show that the proposed algorithm has high optimization accuracy, convergence speed and robustness, and it can generate a more optimized path planning result for UAVs.

Based on multiple datasets and different methods, this manuscript objectively determined the rainy season onset (RSO) over the Southeast Asia Low-Latitude Highlands (SEALLH) and investigated the relationship between RSO and spring drought. The RSO date is defined as the minimum of the rainfall departure over the SEALLH, with a mean value of 11 May and a standard deviation of 15 days. The RSO demarcates the transition between the dry and wet seasons, which is an effective indicator of the sudden emergence of rainfall and convection over the SEALLH. A delayed RSO is characterized by a reduction in April-May rainfall, accompanied by low-level divergence, descending motion and adiabatic warming, decreased cloud cover and increased solar radiation. Consequently, a delayed RSO is frequently associated with spring drought over the SEALLH due to the resulting water deficiency, warmer temperature, and increased evaporation.

Emerging evidence suggests that astrocyte loss is one of the most important pathological features in the hippocampus of patients with major depressive disorder (MDD) and depressive mice. Pyroptosis is a recently discovered form of programmed cell death depending on Caspase–gasdermin D (Casp-GSDMD), which is involved in multiple neuropsychiatric diseases. However, the involvement of pyroptosis in the onset of MDD and glial pathological injury remains obscure. Here, we observed that depressive mice showed astrocytic pyroptosis, which was responsible for astrocyte loss, and selective serotonin reuptake inhibitor (SSRI) treatment could attenuate the pyroptosis induced by the chronic mild stress (CMS) model. Genetic KO of GSDMD, Casp-1, and astrocytic NOD-like receptor protein 3 (NLRP3) inflammasome in mice alleviated depression-like behaviors and inhibited the pyroptosis-associated protein expression. In contrast, overexpression of astrocytic GSDMD–N-terminal domain (GSDMD-N) in the hippocampus could abolish the improvement of behavioral alterations in GSDMD-deficient mice. This work illustrates that targeting the NLRP3/Casp-1/GSDMD–mediated pyroptosis may provide potential therapeutic benefits to stress-related astrocyte loss in the pathogenesis of depression.

The decoupling of crop and livestock in space is currently threatening the sustainable development of agriculture. One of the major challenges is to identify the imbalanced space between cropland and livestock farms. This paper proposes a new methodology to identify such areas at the raster scale, without being limited by traditional administrative division restrictions. The method takes into account nutrient flow, economic cost, and spatial distributions of cropland and livestock farms. The methodology was applied to the Heihe River Basin of China as an example. First, we calculated the nutrient demands on croplands and the supply of livestock manure. Second, we proposed a new method to capture the imbalanced space between cropland and livestock farms. The method was improved on the Gaussian two-step floating catchment area (2SFA) method. To our knowledge, this is the first time such a method has been applied in agriculture. Third, we applied the maximum coverage model to select sites for manure transfer hubs in the imbalanced space of cropland and livestock farms. In this way, the distance of transferring manure can be effectively reduced. Our results showed that the total amount of manure nutrients was sufficient to meet the requirements of local crops in over 90% of the counties located within the Basin. Despite the potential benefits of manure as a fertilizer, its adoption could be more expensive than chemical fertilizers on almost 92% of the croplands due to the high transportation costs associated with spatial separation. However, the identification of 119 transfer hub sites significantly enhanced the accessibility of manure for returning to croplands, ultimately resulting in the optimization of 32% of the previously imbalanced spatial relationship between cropland and livestock farms. The method facilitates raster-scale identification of imbalanced space between cropland and livestock farms, with wide applicability across regions globally.

Chemoresistance is a severe outcome among patients with ovarian cancer that leads to a poor prognosis. MCL1 is an antiapoptotic member of the BCL-2 family that has been found to play an essential role in advancing chemoresistance and could be a promising target for the treatment of ovarian cancer. Here, we found that deubiquitinating enzyme 3 (DUB3) interacts with and deubiquitinates MCL1 in the cytoplasm of ovarian cancer cells, which protects MCL1 from degradation. Furthermore, we identified that O6-methylguanine- DNA methyltransferase (MGMT) is a key activator of DUB3 transcription, and that the MGMT inhibitor PaTrin-2 effectively suppresses ovarian cancer cells with elevated MGMT-DUB3-MCL1 expression both in vitro and in vivo. Most interestingly, we found that histone deacetylase inhibitors (HDACis) could significantly activate MGMT/DUB3 expression; the combined administration of HDACis and PaTrin-2 led to the ideal therapeutic effect. Altogether, our results revealed the essential role of the MGMT-DUB3-MCL1 axis in the chemoresistance of ovarian cancer and identified that a combined treatment with HDACis and PaTrin-2 is an effective method for overcoming chemoresistance in ovarian cancer.

Tea polysaccharide (TPS) is a naturally occurring polysaccharide that has garnered increasing attention due to its remarkable biological activity and significant potential for application. This study focused on examining the alterations in gut microbiota composition and the physiological health of mice subjected to TPS exposure. In this study, a control group (CTRL), a high-dose TPS group (TPH), and a low-dose TPS group (TPL) were established to investigate the effects of TPS on the physiological condition of the intestinal microbiota, liver, intestines, and blood in mice. The findings indicated that TPS significantly increased the relative abundance of beneficial probiotics, including Bacteroidota and Muribaculum , while concurrently diminishing the relative abundance of detrimental intestinal bacteria such as Prevotella_copri and Desulfovibrionia . Additionally, with respect to health indicators, TPS was found to effectively lower the glutamate-glutamate ratio (AST/ALT) and creatine kinase (CK). Serum amylase (AMY) and glucose (Glu) levels were elevated in TPH mice, suggesting improved glucose metabolism. Beta-diversity analysis showed distinct clustering of microbial communities in TPL group, though alpha diversity remained unchanged across groups. Histopathological analysis confirmed no adverse effects on liver or intestinal integrity. Correlation heatmaps highlighted significant associations between gut microbiota (e.g., Bacteroides_H ) and metabolic markers (e.g., CO 2 , AMY). These findings underscore TPS’s role in reshaping gut microbiota, enhancing metabolic health, and mitigating inflammation.

Gynaecological cancer is a main subtype of cancer in women, and acquired chemoresistance is a major contributor to the poor prognosis of gynaecological cancer, but its underlying mechanism remains ill-defined. JOSD1 has been recognized as a deubiquitinase, but its biological functions remain largely unknown, especially in the context of cancer. Here we established a chemoresistant xenograft model and acquired chemoresistant cell lines to mimic the establishment of acquired chemoresistance. We identified that JOSD1 is the most upregulated DUB during the development of chemoresistance. JOSD1 depletion led to severe apoptosis in gynaecological cancer cells both in vivo and in vitro. Mechanistically, we showed that JOSD1 deubiquitinated and stabilized MCL1 to suppress mitochondrial apoptotic signalling. JOSD1 overexpression caused chemoresistance in gynaecological cancer by upregulating the MCL1 protein. Importantly, high JOSD1 expression was correlated with poor prognosis among ovarian cancer patients, and serum JOSD1 levels could be a marker for clinical diagnosis. Our study showed that JOSD1 is a novel and critical oncogene that contributes to the acquisition of chemoresistance by inhibiting mitochondrial apoptotic signalling via MCL1 stabilization. We also suggest that JOSD1 is an ideal therapeutic target and a promising diagnostic marker.