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Abstract Lake is an important water resources in Mongolia, which has undergone a large variation in past decades. However, it is still challenging to monitor long-term changes in lake water storage (LWS) due to the lack of lake level monitoring and long-term satellite altimetry data for Mongolian lakes. According to the Advanced Land Observing Satellite Digital Elevation Model (ALOS DEM) and the Joint Research Centre (JRC) dataset, we estimated the LWS changes of 55 Mongolian lakes (> 10 km2) from 1991 to 2020. The results showed that the LWS increased by 40.24 km3 from 1991 to 1997, especially for northwestern Mongolia with 31.47 km3. However, the LWS decreased by 32.44 km3 from 1998 to 2010, and the lakes in the northwestern and southern decreased by 20.24 km3 (62%) and 7.38 km3 (23%), respectively, and then the LWS continued to decrease by 10.22 km3 from 2011 to 2020. The precipitation was the primary cause of lake change, which could explain 45.13% of LWS change based on Generalized Linear Model, followed by temperature (26.33%) and irrigated area (16.72%). Analyzing the changing characteristic and driving mechanisms of LWS can provide a scientific basis for local water resources management and planning.

Paralytic shellfish toxins (PSTs) pose significant ecological and food safety hazards in China and the world. Consequently, there is a global consensus to intensify safety monitoring of these toxins to safeguard consumers. In recent years, the occurrence of harmful algal blooms (known as "red tides") has increased due to human activities and climate change. The contamination risk posed by PSTs is a pressing concern. This problem poses significant ecological and food safety risks in China and the world, leading to a global consensus on strengthening the safety monitoring of PSTs to ensure consumer safety. Several countries and regions, including the European Union, the United States, and Canada, have established strict regulatory limits (800 μg STXeq/kg) for PSTs and implemented monitoring programs. Currently, the main methods for detecting and monitoring PSTs include enzyme-linked immunosorbent assay, mouse bioassay, high-performance liquid chromatography, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among them, LC-MS/MS has gained international attention due to its high throughput and sensitivity, allowing detailed analysis of toxin profiles in contaminated shellfish. However, the complexity of aquatic food matrices often introduces interference during detection, affecting the accuracy and precision of the results. Using matrix reference materials as quality controls during the analysis can effectively mitigate the errors caused by matrix effects. In recent years, research has been conducted in China on the preparation techniques of matrix reference materials. However, existing techniques have limitations, such as unstable raw materials, limited toxin types, and lack of commercial production. There is still a lack of PST standard materials in China that possess traceability, certification, and physical specimens. To meet the quality control and validation needs for PST detection and analysis, and to enhance the regulation of shellfish quality and safety, the preparation of various PST matrix reference materials has become a top priority.In this study, six PST-producing algae species from four major Chinese coastal areas were compared as the raw material for toxin production: Alexandrium catenella (GY-H25), Gymnodinium catenatum (GY-H65), Alexandrium tamarense (GY-H31 and AT5-3), Alexandrium pacificum (TI0989), and Alexandrium minutum (GY-H46). Through three-step extended culture, all strains achieved mean cell densities ranging from 4.0 × 106 to 4.0 × 107 cells/L. Single cell toxin producing capacity was ordered from highest to lowest as GY-H46, GY-H31, AT5-3, GY-H25, GY-H65, and TI0989. After comparing the toxin production per cell, algal cell density, and toxin composition of the six strains, GY-H46, GY-H31, GY-H25, and GY-H65 were selected for the exposure experiments. These four species of toxic algae (up to 1.0 × 105 cells) were fed to mussels (Mytilus galloprovincialis) for 7 days under controlled conditions. The results demonstrated that the toxin composition of contaminated mussels clustered with those of the causative algae and may separate from one another significantly during the different accumulation phases. GY-H46, GY-H31, and GY-H25 showed consistent toxin profiles with those found in mussels, but varied in the proportions of individual toxin components. GY-H65 exhibited significant differences in toxin composition and proportions in mussels. We also detected a new conversion component (dcSTX) with a maximum proportion of 29.6%. The proportion of dcNEO increased from 1.9% to 13.2% in GY-H65 and mussels. In addition, a high proportion of conversion from C2 to C1 was observed in mussels fed GY-H25 and GY-H65. The mean accumulation rates of toxins from the four toxic algae species in mussels ranged from 39.7% to 83.1%, with the highest toxicity reaching (1, 151.0 ± 7.6) μg STXeq/kg in mussels. Individual exposure experiments with the four toxic algae species demonstrated that mussels are capable of accumulating multiple components and high levels of PSTs. Based on the above observations, the feeding ratios of the low- and high-density groups in the mixed exposure experiment were determined as 1∶1∶1 ∶4 and 1∶1.6∶2.4∶8 for GY-H25, GY-H65, GY-H31, and GY-H46, respectively. The total algae feeding amount per mussel per day was 3.5 × 104 cells in the low-density group and 2.6 × 105 cells in the high-density group. When examining the PST content in mussels from the two mixed exposure groups, it was observed that the mean accumulation conversion rates were comparable at 41.4% and 44.6%, which were lower than the theoretical rates of 48.7% and 47.5%, respectively. The overall toxicity of the low- and high-density groups was (535.0±5.6) and (2, 636.0±12.4) μg STXeq/kg, respectively. After mixed exposure, both experimental groups of mussels accumulated a total of 12 PST components (NEO, dcSTX, dcNEO, GTX1, GTX4, GTX2, GTX3, GTX5, dcGTX2, dcGTX3, C1, and C2).This study demonstrates that mixed exposure of mussels to four toxin-producing algae species, namely A. catenella, A. tamarense, G. catenatum, and A. minutum, can result in the stable and manageable presence of 12 PST components. This provides technical support for the preparation of matrix reference materials that can be used in industrial regulation and industry services. The development of a preparation technology for matrix reference materials with multiple PST components, which do not exceed international limits, holds promise for water quality monitoring and the assessment of marine pollution risks, and provides reference materials for theoretical studies on PSTs risk formation mechanisms.

Paralytic shellfish toxins (PSTs) are a class of neurotoxic marine biotoxins that are widely distributed and cause more than 2, 000 poisoning events worldwide each year, with mortality rates of up to 15%. PSTs can accumulate through the food chain and are mainly distributed in marine organisms such as bivalve mollusks. Several countries and regions, including the European Union, China, and the United States, have established strict regulatory limits (400 MU/100 g or 800 μg STXeq/kg) for PSTs and implemented monitoring programs. As reported previously, factors such as filtration rate, selective feeding, and the efficiency of the organism in absorbing toxin-producing algae can significantly affect the accumulation of PSTs in bivalve mollusks. Mytilus unguiculatus is one of three major commercial mussel species in China, with important economic value and social impact. Due to its high nutritional value, it is extensively cultured as an important shellfish species in the Zhoushan archipelago of Zhejiang Province in China. Alexandrium spp. are the main toxin-producing algae in the area. PSTs have been detected in mussels between May and July after harmful algal blooms. Research into the elimination characteristics of PSTs accumulation in M. unguiculatus is urgently needed to establish a monitoring and control program.In this study, 760 mussels were randomly selected and fed A. catenella at different cell densities, with a high-density group (7.00×105 cells/d), a low-density group (2.80×105 cells/d), and a control group. The experimental period lasted for 30 d, during which the accumulation period approximately represented days 1–7 and the elimination period days 8–30 d. A total of 14 sampling points were set up on days 0.5, 1, 2, 4, 6, and 7 of the accumulation period and days 1, 3, 5, 7, 11, 15, 19, and 23 of the elimination period. Six mussels were randomly collected at each sampling point and dissected into soft tissues, hepatopancreas, and edible tissues. Liquid chromatography-tandem mass spectrometry was used to determine the content of PSTs. During the accumulation period, 5 mL culturing seawater was collected during or 1 h after feeding, and Ruge's solution was added. The filtration rate of the mussels was determined by counting the quantity of A. catenella cells in the water. The results showed that the toxins in M. unguiculatus were not equally distributed. The highest PST content in hepatopancreas tissues was 7, 458.2 μg STXeq/kg (high-density group) and 2, 555.9 μg STXeq/kg (low-density group). The highest PST content in edible tissues was 108.6 μg STXeq/kg (high-density group). The hepatopancreas was identified as a target organ for toxin accumulation. From day 3 to day 7, the filtration rate of mussels decreased, eventually reaching 30% of its initial value. The filtration rate of M. unguiculatus in the high-density group was not significantly different from that of the low-density group during days 1–5 and was significantly lower during days 5–7. During the elimination phase, the PST elimination rate in mussels was 18.4% (hepatopancreas), 18.1% (soft tissues), and 13.1% (edible tissues). At day 30, the residual content of PSTs in the hepatopancreas of mussels was approximately 1 400 μg STXeq/kg in the high-density group and 600.0 μg STXeq/kg in the low-density group. Changes in the proportion of each PST component were transferred from A. catenella to M. unguiculatus. The proportion of C2 was significantly reduced from 74.1% (A. catenella) to 22.6% (high-density group) and 17.1% (low-density group) (P < 0.05); the percentage of C1 increased from 10.6% (A. catenella) to 54.1% (high-density group) and 54.0% (low-density group) (P < 0.05). No significant difference was observed in the percentage of GTX5 between A. catenella and mussels in the different density groups (P > 0.05). No significant conversion was observed between the PST components in the hepatopancreas of mussels throughout the experiment.Our data indicate that the daily accumulation rate of PSTs in M. unguiculatus was lower than that in other mussels. Moreover, the toxin elimination rate was higher than that of other mussels. A negative correlation was observed between the filtration rate of M. unguiculatus and the PST content of each tissue type. These results show that M. unguiculatus is more sensitive to PSTs than other mussels. During the stage of PST transfer from A. catenella to M. unguiculatus, a high proportion of C2 toxin was converted to C1 toxin. After accumulating in the hepatopancreas, the PST profile exhibited relatively stable performance. In summary, we conclude that, due to higher susceptibility to toxins and lower conversion rates, a lower risk is associated with the consumption of M. unguiculatus than with that of other mussels. Our findings will contribute to improving our understanding of the mechanisms underlying the PST accumulation risk in M. unguiculatus and provide valuable scientific insights for developing prevention and risk management strategies concerning PSTs.

Abstract Background In addition to functioning as a precise monitoring mechanism in cell cycle, the anaphase-promoting complex/cyclosome (APC/C) is reported to be involved in regulating multiple metabolic processes by facilitating the ubiquitin-mediated degradation of key enzymes. Fatty acid oxidation is a metabolic pathway utilized by tumor cells that is crucial for malignant progression; however, its association with APC/C remains to be explored. Methods Cell cycle synchronization, immunoblotting, and propidium iodide staining were performed to investigate the carnitine palmitoyltransferase 1 C (CPT1C) expression manner. Proximity ligation assay and co-immunoprecipitation were performed to detect interactions between CPT1C and APC/C. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium, inner salt (MTS) assays, cell-scratch assays, and transwell assays and xenograft transplantation assays were performed to investigate the role of CPT1C in tumor progression in vitro and in vivo. Immunohistochemistry was performed on tumor tissue microarray to evaluate the expression levels of CPT1C and explore its potential clinical value. Results We identified CPT1C as a novel APC/C substrate. CPT1C protein levels exhibited cell cycle-dependent fluctuations, peaking at the G1/S boundary. Elevated CPT1C accelerated the G1/S transition, facilitating tumor cell proliferation in vitro and in vivo. Furthermore, CPT1C enhanced fatty acid utilization, upregulated ATP levels, and decreased reactive oxygen species levels, thereby favoring cell survival in a harsh metabolic environment. Clinically, high CPT1C expression correlated with poor survival in patients with esophageal squamous cell carcinoma. Conclusions Overall, our results revealed a novel interplay between fatty acid utilization and cell cycle machinery in tumor cells. Additionally, CPT1C promoted tumor cell proliferation and survival by augmenting cellular ATP levels and preserving redox homeostasis, particularly under metabolic stress. Therefore, CPT1C could be an independent prognostic indicator in esophageal squamous cell carcinoma.

IntroductionAutoimmune encephalitis (AE) comprises a group of inflammatory brain disorders mediated by autoimmune responses. Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis, anti–leucine-rich glioma-inactivated 1 (LGI1) encephalitis, and anti–γ-aminobutyric acid-B receptor (GABABR) encephalitis are the most prevalent forms, characterized by the presence of antibodies against neuronal cell-surface antigens. Efgartigimod, an antagonist of the neonatal Fc receptor, has proven efficacy in myasthenia gravis treatment. This clinical case report describes the clinical progression and functional outcomes of AE in three patients who received efgartigimod treatment.Case presentationsCase 1 was a 60-year-old man exhibiting memory impairment and psychiatric disturbances over 11 days. Case 2 was a 38-year-old man with a 1-month history of rapid cognitive decline and seizures. Case 3 was a 68-year-old woman with mental behavioral changes and seizures for 4 months. Anti-GABABR, anti-LGI1, and anti-NMDAR antibodies were confirmed in the respective patients’ cerebrospinal fluid or serum. All three patients experienced marked and swift symptomatic relief after four cycles of efgartigimod treatment, with no complication.ConclusionCurrent first-line and second-line treatments for AE have limitations, and efgartigimod has demonstrated potential in the rapid and efficacious treatment of AE, emerging as a promising option for the management of this disease.

Cancer patients by immune checkpoint therapy have achieved long-term remission, with no recurrence of clinical symptoms of cancer for many years. Nevertheless, more than half of cancer patients are not responsive to this therapy due to immune exhaustion. Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy. The results showed that PD1-Imi Exo had a vesicular round shape (approximately 139 nm), revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell, and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice. The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8+ T cell with cancer cell, displaying a PD1/PDL1 immune checkpoint blockage effect, and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell, exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8+ T cell. In conclusion, the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy. This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity, thus consolidating the overall prognosis.

Background: There have been no reports about the application of random survival forest (RSF) model to predict disease progression of HIV-associated B-cell lymphoma. Methods: A total of 44 patients with HIV-associated B-cell lymphoma who were referred to Nanjing Second Hospital from 2012 to 2019 were included. The RSF model was used to find predictors of survival, and the results of the RSF model were compared with those of the Cox model. The data were analyzed using R software (version 4.1.1). Results: One-, 2-, and 3-year survival rates were 74.5%, 57.7%, and 48.6%, respectively, and the median survival was 59.0 months. The first 3 most important predictors of survival included lactate dehydrogenase (LDH), absolute monocyte count (AMC), and white blood cells (WBCs) count. The median survival of high-risk patients was only 4.0 months. Areas under the curve (AUCs) of the RSF model remained at more than 0.90 at 1, 2, and 3 years. The RSF model displayed a lower prediction error rate (21.9%) than the Cox model (25.4%). Conclusions: Lactate dehydrogenase, AMC, and WBCs count are the most important prognostic predictors for patients with HIV-associated B-cell lymphoma. Much larger prospective and/or multicentre studies are required to validtae this RSF model.

Sea ice concentration (SIC) is an important dimension for characterising the geographical features of the pan-Arctic region. Trends in SIC bring new opportunities for human activities in the Arctic region. In this paper, we propose a deep learning technology-based sea ice concentration prediction model, SICFormer, which can realise end-to-end daily sea ice concentration prediction. Specifically, the model uses a 3D-Swin Transformer as an encoder and designs a decoder to reconstruct the predicted image based on PixelShuffle. This is a new model architecture that we have proposed. Single-day SIC data from the National Snow and Ice Data Center (NSIDC) for the years 2006 to 2022 are utilised. The results of 8-day short-term prediction experiments show that the average Mean Absolute Error (MAE) of the SICFormer model on the test set over the 5 years is 1.89%, the Root Mean Squared Error (RMSE) is 5.99%, the Mean Absolute Percentage Error (MAPE) is 4.32%, and the Nash–Sutcliffe Efficiency (NSE) is 0.98. Furthermore, the current popular deep learning models for spatio-temporal prediction are employed as a point of comparison given their proven efficacy on numerous public datasets. The comparison experiments show that the SICFormer model achieves the best overall performance.

As the world’s first large grain crop, wheat in its mechanized harvesting process faces a serious problem, namely, when the combine harvester operating parameters are not set reasonably, it leads to increased losses of wheat kernels to an extent exceeding the prescribed standard, of which the loss of scavenging accounts for a large proportion. Excessive grain harvest loss will not only reduce the quality of the wheat harvest but also adversely affect its yield. Real-time monitoring of losses in the harvesting process is key to the dynamic adjustment of operating parameters to decrease machine harvesting losses. This article proposes a grain cleaning loss monitoring device for combine harvesters suitable for wheat crops. It aims to measure the loss of grain cleaning in the process of wheat harvesting in real time and adjust the operating parameters of the harvester timeously by feeding back the data to the driver in real time, so as to decrease the loss of wheat grains in the process of harvesting and achieve the purpose of reducing the loss of harvest. When the device was tested in the field, the wheat variety was Bainong 4199, the yield per mu was 625.83 kg (one mu is 1/15 of a hectare, or approximately 666.67 m2), the mass of grain was 43.21 g, and the water content was 14.2%. After the test, the monitoring error of the loss monitoring device was within 8%, and the average error rate was 6.69%. The test proves that the monitoring device achieves the expected design effect and meets design requirements. The results of this paper are of significance to the intelligent control system of wheat combine harvesters and provide a reference for research into grain cleaning loss monitoring devices for wheat combine harvesters.

Revealing the spatial–temporal evolution of carbon storage and its driving mechanisms in the Qinghai–Tibet Plateau could provide support for decision making in the protection of regional ecosystems and the achievement of regional dual-carbon goals. In this study, the spatial–temporal evolution of carbon storage in the Qinghai–Tibet Plateau was analyzed under various scenarios using PLUS-InVEST and a gravity center model, and the driving mechanisms of carbon storage were clarified with Geodetector. The results are as follows: (1) During 2000–2020, the areas of coniferous forest, evergreen broad-leaved forest, closed shrub, temperate shrub desert, multi-tree grassland, and grassland showed an increasing trend, while the areas of deciduous broad-leaved forest and mixed forest showed a decreasing trend. (2) During 2030–2060, there was a decreasing trend in the total carbon storage of the Qinghai–Tibet Plateau under three different scenarios. (3) During 2030–2060, the area of the Qinghai–Tibet Plateau was mostly represented by carbon balance (56%), while the areas of carbon sources and carbon sinks showed a scattered distribution. (4) The precipitation and topographic factors with a q value of 0.888 played a dominant role in affecting the spatio-temporal variations in carbon storage in the Qinghai–Tibet Plateau. (5) In future ecological protection and restoration efforts, more high-quality farmlands should be protected and constructed, which could contribute to the achievement of dual-carbon goals. In addition, the hydrothermal conditions should be improved to aid the carbon cycle process in the Qinghai–Tibet Plateau.

Phytopathogenic fungi normally secrete large amounts of CWDEs to enhance infection of plants. In this study, we identified and characterized a secreted glycosyl hydrolase 5 family member in Sclerotinia sclerotiorum (SsGH5, Sclerotinia sclerotiorum Glycosyl Hydrolase 5). SsGH5 was significantly upregulated during the early stages of infection. Knocking out SsGH5 did not affect the growth and acid production of S. sclerotiorum but resulted in decreased glucan utilization and significantly reduced virulence. In addition, Arabidopsis thaliana expressing SsGH5 became more susceptible to necrotrophic pathogens and basal immune responses were inhibited in these plants. Remarkably, the lost virulence of the ΔSsGH5 mutants was restored after inoculating onto SsGH5 transgenic Arabidopsis. In summary, these results highlight that S. sclerotiorum suppresses the immune responses of Arabidopsis through secreting SsGH5, and thus exerts full virulence for successful infection.