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Abstract Arcopilus aureus is a plant-beneficial fungal species showing remarkable biocontrol capabilities. We investigated the antifungal activity of A. aureus YZXR strain and found that it strongly suppressed Polygonatum odoratum leaf spot disease caused by Fusarium fujikuroi. However, the antifungal substances and antifungal mechanisms remain unknown. To identify the antifungal substances, we extracted the fermentation liquid with ethyl acetate and found that the antifungal activity was mainly in the organic phase. Using column chromatography, semi-preparative HPLC, and GC–MS assays, we analyzed the compounds in the ethyl acetate phase and identified phenylethyl alcohol and 3,5-dihydroxytoluene as two compounds showing antifungal activity. The phenylethyl alcohol completely inhibited the growth of F. fujikuroi at a concentration of 0.25% (v/v), whereas the inhibition rate of 10.00 mg/mL 3,5-dihydroxytoluene on fungal growth was 80.60%. The fermentation broth of strain YZXR efficiently inhibited mycelial growth and conidiation of F. fujikuroi. Thus, this study uncovered the antifungal metabolites of A. aureus and the potential of A. aureus as a biological fungicide for managing P. odoratum leaf spot disease, providing a foundation for further research on its biocontrol mechanisms and field applications.

Abstract Background Overcoming resistance to Osimertinib in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) is clinically challenging because the underlying mechanisms are not fully understood. The murine double minute 2 (MDM2) has been extensively described as a tumor promotor in various malignancies, mainly through a negative regulatory machinery on the p53 tumor suppressor. However, the significance of MDM2 on the sensitivity to Osimertinib has not been described. Methods Osimertinib resistant cells were generated by standard dose escalation strategy and individual resistant clones were isolated for MDM2 testing. The MDM2 and its mutant constructs (ΔPBD, ΔRING, C464A) were introduced into PC-9, HCC827 and H1975 cells and evaluated for the sensitivity to Osimertinib by MTT assay, colony formation, EdU assay and TUNEL assay. MDM2 expression in resistant cells was manipulated by pharmacological and molecular approaches, respectively. Proteins that were implicated in PI3K/Akt, MAPK/Erk and apoptosis signaling were measured by Western blot analysis. Candidate proteins that interacted with MDM2 were captured by immunoprecipitation and probed with indicated antibodies. Results In comparison with parental PC-9 cells, the PC-9 OR resistant cells expressed high level of MDM2. Ectopic expression of MDM2 in PC-9, HCC827 and H1975 sensitive cells generated an Osimertinib resistant phenotype, regardless of p53 status. MDM2 promoted resistance to Osimertinib through a PI3K/Akt and MAPK/Erk-independent machinery, in contrast, MDM2 selectively stabilized MCL-1 protein to arrest Osimertinib-induced cancer cell apoptosis. Mechanistically, MDM2 acted as a E3 ligase to ubiquitinate FBW7, a well-established E3 ligase for MCL-1, at Lys412 residue, which resulted in FBW7 destruction and MCL-1 stabilization. Targeting MDM2 to augment MCL-1 protein breakdown overcame resistance to Osimertinib in vitro and in vivo. Finally, the clinical relevance of MDM2-FBW7-MCL-1 regulatory axis was validated in mouse xenograft tumor model and in NSCLC specimen. Conclusion Overexpression of MDM2 is a novel resistant mechanism to Osimertinib in EGFR mutant NSCLC. MDM2 utilizes its E3 ligase activity to provoke FBW7 destruction and sequentially leads to MCL-1 stabilization. Cancer cells with aberrant MDM2 state are refractory to apoptosis induction and elicit a resistant phenotype to Osimertinib. Therefore, targeting MDM2 would be a feasible approach to overcome resistance to Osimertinib in EGFR mutant NSCLC.

Abstract Dryland agriculture is fundamental to global crop production and vital to food security. Conservation tillage is extensively practiced in USA wheat cultivation. Meanwhile, the adoption of conservation tillage by Chinese farmers is limited. This meta-analysis compared the yield and nitrogen use efficiency (NUE) between conservation tillage and conventional tillage (CT) with different types of cropping systems, mulching methods, levels of nitrogen fertilizer (NF), and addition of manure. The meta-analysis presented that conservation tillage at high-NF enhanced the yield and NUE, and reduced the yield and NUE at low-NF, compared to CT. The interaction of conservation tillage with leguminous cover crops (LCC) and manure application increased the yield and NUE at low-NF, compared to CT. Non-leguminous cover crops (NLCC) increased the yield and NUE under high-NF than low-NF. The interaction of conservation tillage with management practices showed that the no-tillage (NT) with leguminous cover crops (LCC) significantly increased wheat yield by 58% and NUE by 47% under low-NF compared to CT. However, increasing the rate of NF did not increase the yield under such interaction. Cropping systems, mulching types, and manure application mainly determined the effects of conservation tillage on wheat yield and NUE. The adverse impact of CT on yield and NUE could be alleviated with the application of LCC and manure under moderate NF. We demonstrate that adding LCC and manure have a generally substitutive relationship with N fertilizer, resulting in a significant increase in wheat yield and NUE at low-NF doses as at high N fertilizer dosages. Therefore, based on the obtained results, moderate NF with LCC and manure application is recommended for growing winter wheat in dryland regions of the USA and China.

Abstract Background Drought stress is a significant abiotic stressor that hinders growth, development, and crop yield in soybeans. Strigolactones (SLs) positively regulate plant resistance to drought stress. However, the impact of foliar application of SLs having different concentrations on soybean growth and metabolic pathways related to osmoregulation remains unknown. Therefore, to clarify the impact of SLs on soybean root growth and cellular osmoregulation under drought stress, we initially identified optimal concentrations and assessed key leaf and root indices. Furthermore, we conducted transcriptomic and metabolic analyses to identify differential metabolites and up-regulated genes. Results The results demonstrated that drought stress had a significant impact on soybean biomass, root length, root surface area, water content and photosynthetic parameters. However, when SLs were applied through foliar application at appropriate concentrations, the accumulation of ABA and soluble protein increased, which enhanced drought tolerance of soybean seedlings by regulating osmotic balance, protecting membrane integrity, photosynthesis and activating ROS scavenging system. This also led to an increase in soybean root length, lateral root number and root surface area. Furthermore, the effects of different concentrations of SLs on soybean leaves and roots were found to be time-sensitive. However, the application of 0.5 µM SLs had the greatest beneficial impact on soybean growth and root morphogenesis under drought stress. A total of 368 differential metabolites were screened in drought and drought plus SLs treatments. The up-regulated genes were mainly involved in nitrogen compound utilization, and the down-regulated metabolic pathways were mainly involved in maintaining cellular osmoregulation and antioxidant defenses. Conclusions SLs enhance osmoregulation in soybean plants under drought stress by regulating key metabolic pathways including Arachidonic acid metabolism, Glycerophospholipid metabolism, Linoleic acid metabolism, and Flavone and flavonol biosynthesis. This study contributes to the theoretical understanding of improving soybean adaptability and survival in response to drought stress.

Abstract Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs. Graphical abstract

Renal cell carcinoma (RCC) is a type of tumor with high morbidity and recurrence rates. The application of circulating tumor cells (CTCs) in RCC remains controversial. Hence, we performed a meta-analysis to elucidate the diagnostic and prognostic value of CTCs in RCC. To obtain a precise conclusion, a systematic search was conducted in Pubmed, Cochrane Database, Embase and Web of Science up to Dec 01, 2022. We also further identified the references in relevant studies. The diagnostic accuracy variables (sensitivity, specificity) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to access precise of CTCs and relationship between CTCs and disease stages, respectively. Heterogeneity test, sensitivity analysis, meta-regression and publishing bias were also applied. A total of 12 studies involving 767 patients were considered to be included in the final meta-analysis. The results revealed that the overall sensitivity, specificity of CTC detection in RCC were 45% (95%CI, 32-60%) and 99% (95%CI, 97-100%), respectively. In subgroup analysis, diagnostic sensitivity of CTCs in clear cell renal cell carcinoma (ccRCC) (69%, 95%CI; 50-88%) was significantly higher than other RCC subtypes (34%, 95%CI; 21-48%) (p

As intelligent ship technology advances, the importance of intelligent anchor position detection, as one of the key technologies, can ensure the safe anchoring of ships and enhance the efficiency of port operation. At present, most of the anchor position selection and detection algorithms are mainly based on two-dimensional planes, and there is a lack of research on the intelligent detection of safe water depth for ship anchoring in three-dimensional space. It not only restricts the full utilization of anchorage resources but also affects the safety and environmental adaptability of anchoring operations. To address these issues, this study proposes a three-dimension anchor position detection method. Firstly, based on the establishment of a three-dimensional ocean model, the possible anchor positions selected by the ship are simulated using the Monte Carlo algorithm. Secondly, the simulated anchor positions are optimized using a Traversal algorithm to filter out the optimal anchoring position that meets the requirements, the safety distance between each point and the existing ship is calculated, and the anchor position is determined according to the corresponding required safety spacing. Finally, to verify the applicability and effectiveness of the method under different sea conditions and different ship types, this study conducts a series of simulation experiments with 5000 random samples. These experiments compare the demand of anchor position selection for anchoring ships with changing water depths in the case of empty and full load drafts, and visualize the impact of varying water depth parameters on the selection of anchor positions for anchoring ships in various ship types. The outcomes of the experiment indicate that the algorithm’s detection area encompasses the whole anchorage area, ensuring both the anchorage area’s usage rate and the accuracy of anchor position detection. This study demonstrates that the Traversal and Monte Carlo Algorithms effectively improve the accuracy of the selection of anchoring position of the ship, makes full use of the resources of anchorage, and further improves the safety and efficiency of the anchoring operation.

Flexible pressure sensors applied in wearable detection often face challenges, such as low sensitivity, large device size, poor flexibility, and long response time. This study aims to design and develop high-performance pressure-sensitive materials for wearable human detection applications. Using a sensitive layer composite and microstructural design, rGO/Fe nanowires (NWs) composites were proposed as the pressure-sensitive material. This approach yields a compact sensor with high flexibility, good mechanical properties, and excellent sensing performance. Firstly, rGO/Fe NWs composites were prepared by the Hummers method and an in situ reduction technique under a magnetic field. Secondly, the structural design, component construction, and sensing mechanism of the sensors were thoroughly investigated. Finally, the performance of the flexible pressure sensor was tested, and its application in the wearable field was explored. The results demonstrate that the sensor exhibits excellent performance with a good response to both large and small pressures within the range of 0–30 kPa, providing an effective method for wearable human health detection.

Abstract Chinese rose (Rosa chinensis) is an important ornamental plant, with economic, cultural, and symbolic significance. During the application of outdoor greening, adverse environments such as high temperature and drought are often encountered, which affect its application scope and ornamental quality. The starch phosphorylase (Pho) gene family participate in the synthesis and decomposition of starch, not only related to plant energy metabolism, but also plays an important role in plant stress resistance. The role of Pho in combating salinity and high temperature stress in R. chinensis remains unknown. In this work, 4 Phos from R. chinensis were detected with Pfam number of Pho (PF00343.23) and predicted by homolog-based prediction (HBP). The Phos are characterized by sequence lengths of 821 to 997 bp, and the proteins are predicted to subcellularly located in the plastid and cytoplasm. The regulatory regions of the Phos contain abundant stress and phytohormone-responsive cis-acting elements. Based on transcriptome analysis, the Phos were found to respond to abiotic stress factors such as drought, salinity, high temperature, and plant phytohormone of jasmonic acid and salicylic acid. The response of Phos to abiotic stress factors such as salinity and high temperature was confirmed by qRT-PCR analysis. To evaluate the genetic characteristics of Phos, a total of 69 Phos from 17 species were analyzed and then classified into 3 groups in phylogenetic tree. The collinearity analysis of Phos in R. chinensis and other species was conducted for the first time. This work provides a view of evolution for the Pho gene family and indicates that Phos play an important role in abiotic stress response of R. chinensis.

Abstract Objectives The purpose of our study is to further understanding of the depression symptoms of HIV/AIDS patients in Guilin, Guangxi via exploring whether there is a mediating effect of sleep quality on medical-social support and depression symptoms and therefore provide a theoretical basis for application of medical-social support to alleviate depression symptoms of HIV/AIDS patients. Methods A convenience sampling method was used to select 200 HIV/AIDS patients for the study. Depression symptoms, sleep quality, and medical-social support of the study participants were investigated using The Center for Epidemiological Studies Depression Scale (CES-D), The Pittsburg Sleep Quality Index (PSQI), and The Medical Outcomes Study Social Support Survey (MOS-SSS), respectively. Predictors of depression symptoms were explored by multiple linear regression, and Pearson correlation was used to analyze the relationship between sleep quality, medical-social support, and depression symptoms. Mediating effect analysis was performed by nonparametric Bootstrap test. Results In this study, the incidence of depression symptoms was 54.4%. Multiple linear regression analysis showed that leanness (β = 0.161, P = 0.008), obesity (β = 0.186, P = 0.002), sleep quality score > 7 (β = 0.331, P 56 (β = -0.247, P

Abstract While the monolayer sheet is well-established as a Mott-insulator with a finite energy gap, the insulating nature of bulk 1T-TaS2 crystals remains ambiguous due to their varying dimensionalities and alterable interlayer coupling. In this study, we present a unique approach to unlock the intertwined two-dimensional Mott-insulator and three-dimensional band-insulator states in bulk 1T-TaS2 crystals by structuring a laddering stack along the out-of-plane direction. Through modulating the interlayer coupling, the insulating nature can be switched between band-insulator and Mott-insulator mechanisms. Our findings demonstrate the duality of insulating nature in 1T-TaS2 crystals. By manipulating the translational degree of freedom in layered crystals, our discovery presents a promising strategy for exploring fascinating physics, independent of their dimensionality, thereby offering a “three-dimensional” control for the era of slidetronics.

Abstract Objectives This study aims to gather and analyze the anatomical characteristics of the posterior gastric artery (PGA), investigate the presence and metastasis of lymph nodes around the PGA in patients with gastric cancer. Additionally, the study aims to analyze the relationship between the PGA and its surrounding lymph nodes and the clinicopathological features of patients with gastric cancer. Methods This study consisted of a cross-sectional analysis of data from 52 patients with gastric cancer who underwent total or proximal gastrectomy at the Department of Gastrointestinal Surgery, First Affiliated Hospital of Dalian Medical University, between January 2020 and November 2022. Intraoperative exploration was performed to determine the presence of the PGA, and patients with the PGA were assessed for relevant anatomical characteristics, including the length of the PGA and the distance from the root of the PGA to the celiac trunk. Dissection of lymph nodes around the PGA was also performed. Statistical methods were employed to describe and analyze the data regarding the presence of the PGA, as well as the presence and metastasis of the lymph nodes around the PGA. Additionally, the study identified clinicopathological factors associated with these conditions. Results The PGA was identified in 39 (75.0%) out of 52 patients with gastric cancer, exhibiting a mean PGA length of 3.5 ± 0.8 cm and a mean distance from the root of the PGA to the celiac trunk of 6.7 ± 1.7 cm. Among the 39 patients who underwent dissection of lymph nodes around the PGA, 36 lymph nodes around the PGA were detected in 20 patients. Analysis of factors associated with the presence of lymph nodes around the PGA revealed a significant correlation with the macroscopic type of the tumor and the total number of dissected lymph nodes (P = 0.007 and P = 0.022, respectively), with a larger number of total dissected lymph nodes being an independent factor (OR = 1.105, 95%CI: 1.019–1.199, P = 0.016). Furthermore, analysis of risk factors for metastasis of the lymph nodes around the PGA demonstrated that the total number of metastatic lymph nodes, No.3 lymph node metastasis, and No.11 lymph node metastasis were associated with metastasis of the lymph nodes around the PGA (P = 0.043, P = 0.028, and P = 0.020, respectively). Conclusion The PGA exhibits a high incidence. It is essential to carefully identify the PGA during procedures involving the PGA and consider appropriate preservation or disconnection of this vessel. The presence of lymph nodes around the PGA is not an isolated occurrence. Gastric cancer can result in metastasis of the lymph nodes around the PGA. Although the overall risk of metastasis of the lymph nodes around the PGA is low in patients with gastric cancer, it increases in the presence of conditions such as No.3 lymph node metastasis, No.11 lymph node metastasis, advanced tumor stage, and extensive metastases in other regional lymph nodes.

Abstract Background To investigate the short-term and long-term outcomes of preserving the celiac branch of the vagus nerve during laparoscopic distal gastrectomy. Methods A total of 149 patients with prospective diagnosis of gastric cancer who underwent laparoscopic-assisted distal gastrectomy (LADG) combined with Billroth-II anastomosis and D2 lymph node dissection between 2017 and 2018 were retrospectively analyzed. The patients were divided into the preserved LADG group (P-LADG, n = 56) and the resected LADG group (R-LADG, n = 93) according to whether the vagus nerve celiac branch was preserved. We selected 56 patients (P-LADG, n = 56) with preservation of the celiac branch of the vagus nerve and 56 patients (R-LADG, n = 56) with removal of the celiac branch of the vagus nerve by propensity-matched score method. Postoperative nutritional status, weight change, short-term and long-term postoperative complications, and gallstone formation were evaluated in both groups at 5 years of postoperative follow-up. The status of residual gastritis and bile reflux was assessed endoscopically at 12 months postoperatively. Results The incidence of diarrhea at 5 years postoperatively was lower in the P-LADG group than in the R-LADG group (p

In recent years, the application of textile reinforced mortar (TRM) as an overlay has become an important method for repairing and strengthening old masonry structures. However, the quantitative analysis and design of TRM-strengthened reinforced concrete (RC) beams are still limited. To address this gap, a nonlinear finite element (FE) model is proposed in this study to simulate the flexural behavior of TRM-strengthened RC beams. The developed model is validated using experimental results and subsequently utilized for the design of TRM-strengthened RC beams. Various TRM design parameters, including the number of textile layers, textile longitudinal length, and textile mesh size, are parametrically investigated. The modelling results reveal that increasing the number of textile layers and longitudinal length while decreasing the textile mesh size can enhance the bending strength of TRM-strengthened RC beams. Furthermore, an analytical model is proposed to predict the flexural strength of TRM-strengthened RC beams, facilitating rapid strength estimation of TRM-strengthened RC beams. The predicted results demonstrate good agreement with the numerical simulation results. The established FE models can predict the bending performance of TRM-strengthened RC beams under different reinforcement conditions, and the simulation outcomes can provide valuable guidance for their design.

Canine circovirus (CanineCV) is a recently identified member of the Circoviridae family. Since its discovery in 2011, CanineCV has been detected in different countries worldwide, infecting both domestic and wild canids. The virus is potentially associated with gastrointestinal and respiratory illnesses. In 2016, CanineCV was reported in the southwestern region of Guangxi, China. However, its prevalence in other provinces in the Southwest region remained unknown. This study collected a total of 208 serum samples from domestic dogs in Sichuan, China in 2022 to investigate the prevalence of CanineCV. Among these samples, 26 tested positive for CanineCV, resulting in a positivity rate of 12.5%. Additionally, 12 strains were sequenced, 9 of which had a sequence length of 2,063 nucleotides (nt), 2 of the other threes had a length of 2,062 nts and another was 2,064 nt. Notably, a frameshift mutation was identified, resulting in a truncated ORF1 and the occurrence of a novel sequence comprised of 13 amino acids at the end of the replicate protein (Rep). This mutation could affect the replication cycle of the virus. Phylogenetic and evolutionary analyses revealed that the isolates belonged to the CanineCV-3 genotype and were prevalent in the Southeast and the Southwest regions of China, as well as in the neighboring countries alongside other strains of the same genotype. Collectively, this epidemiological investigation widens our understanding of the genetic diversity of CanineCV in Southwest China and provides insights into viral evolution.

Summary: Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10−6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

Abstract Continuous cropping has a negative effect on soybean yield. In this study, a positioning experiment was conducted starting in 2015, with three treatments: maize–soybean rotation (SMR), 2-year maize, 2-year soybean rotation cropping (SC2), and 8-year soybean continuous cropping (SC8). We determined soybean yields (2015–2022) and analyzed soil microbial communities, functions, and metabolites composition in the 0–20 cm tillage layer using metagenomics technology and GC–MS technology during soybean flowering in 2022. Results indicated that continuous cropping (SC8) significantly reduced soybean yield compared to crop rotation (SMR) during the experimental period, while SC8 showed higher yield than SC2 in 2022. Compared to SMR, SC8 significantly increased soil N content and significantly decreased pH and TP, AP, and AK content. However, the pH and AK contents of SC8 were significantly higher than those of SC2. LeFSe analysis showed that Friedmanniella, Microlunatus, Nitrososphaera, Rubrobacter, Geodermatophilus, Nitriliruptor were enriched in SC8. Gaiella, Sphaerobacter, Methyloceanibacter were enriched in SC2. Sphingomonas, Cryobacterium, Marmoricola, Haliangium, Arthrobacter, Ramlibacter, Rhizobacter, Pseudolabrys, Methylibium, Variovorax were enriched in SMR. And the relative abundance of Cryobacterium, Marmoricola, Haliangium, Arthrobacter, Ramlibacter, Rhizobacter, Methylibium, Variovorax was significantly positively correlated with yield, while the relative abundance of Gaiella and Sphaerobacter was significantly negatively correlated with yield. SC8 significantly increased the abundance of genes in nitrogen metabolism and significantly decreased the abundance of genes related to phosphorus and potassium metabolism compared with SMR. However, the abundance of genes in potassium metabolism was significantly higher in SC8 than in SC2. Metabolomic analysis showed that compared to SMR, SC8 decreased the abundance of carbohydrates, ketones, and lipid. However, the abundance of carbohydrates, ketones, and lipid was significantly higher in SC8 than in SC2. Mantel test showed that soil pH and AK significantly affected soil microbial community, function, and metabolite composition. Correlation analysis showed significant correlation between soil metabolites and microorganisms, metabolic functions. Graphical Abstract

Abstract Electrochemical reduction of carbon dioxide into ethylene, as opposed to traditional industrial methods, represents a more environmentally friendly and promising technical approach. However, achieving high activity of ethylene remains a huge challenge due to the numerous possible reaction pathways. Here, we construct a hierarchical nanoelectrode composed of CuO treated with dodecanethiol to achieve elevated ethylene activity with a Faradaic efficiency reaching 79.5%. Through on in situ investigations, it is observed that dodecanethiol modification not only facilitates CO2 transfer and enhances *CO coverage on the catalyst surfaces, but also stabilizes Cu(100) facet. Density functional theory calculations of activation energy barriers of the asymmetrical C–C coupling between *CO and *CHO further support that the greatly increased selectivity of ethylene is attributed to the thiol-stabilized Cu(100). Our findings not only provide an effective strategy to design and construct Cu-based catalysts for highly selective CO2 to ethylene, but also offer deep insights into the mechanism of CO2 to ethylene.

In aquaculture, quantifying the real-time feeding behaviour of fish is essential for making feeding decisions. However, most existing methods for assessing fish appetite are inefficient and subjective. To address these issues, this study proposes an improved tilapia feeding level classification model with ResNet34. First, we introduce the attention module CBAM into the ResNet34 model to adjust the attention of the model according to the importance of different channel features and enhance the effective extraction of important features. We then used migration learning to transfer the knowledge learned from the source data (ImageNet dataset) to the tilapia ingestion image dataset, which allowed us to train the tilapia ingestion behaviour classification model faster while retaining the pre-trained model. Experimental results showed that the improved ResNet34 model in this study achieved an accuracy of 99.72%, an improvement of 7.84 percentage points over the original model. In addition, the model outperformed models such as MobileNetV2, AlexNet, VGG11, ShuffleNet_v2_x0_5 and ResNet18 in terms of accuracy, precision, recall and F1 scores.These results suggest that the proposed method can accurately identify feeding behavior of fish and provide a scientific basis for determining feeding amounts.

Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen “green” natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

BackgroundThe Chikungunya virus is an Alphavirus that belongs to the Togaviridae family and is primarily transmitted by mosquitoes. It causes acute infection characterized by fever, headache, and arthralgia. Some patients also experience persistent chronic osteoarthritis-like symptoms. Dedicated antiviral treatments are currently unavailable for CHIKV. This study aims to explore the potential anti-CHIKV effect of rosmarinic acid using network pharmacology.MethodsThis study employed network pharmacology to predict and verify the molecular targets and pathways associated with ROSA in the context of CHIKV. The analysis outcomes were further validated using molecular docking and in vitro experiments.ResultsThe analysis of CHIKV targets using the Kyoto Encyclopedia of Genes and Genomes and MCODE identified IL-17 as an important pathogenic pathway in CHIKV infection. Among the 30 targets of ROSA against CHIKV, nearly half were found to be involved in the IL-17 signaling pathway. This suggests that ROSA may help the host in resisting CHIKV invasion by modulating this pathway. Molecular docking validation results showed that ROSA can stably bind to 10 core targets out of the 30 identified targets. In an in vitro CHIKV infection model developed using 293T cells, treatment with 60 μM ROSA significantly improved the survival rate of infected cells, inhibited 50% CHIKV proliferation after CHIKV infection, and reduced the expression of TNF-α in the IL-17 signaling pathway.ConclusionThis study provides the first confirmation of the efficacy of ROSA in suppressing CHIKV infection through the IL-17 signaling pathway. The findings warrant further investigation to facilitate the development of ROSA as a potential treatment for CHIKV infection.

BackgroundLMB-100 is a mesothelin (MSLN)-targeting recombinant immunotoxin (iTox) carrying a Pseudomonas exotoxin A payload that has shown promise against solid tumors, however, efficacy is limited by the development of neutralizing anti-drug antibodies (ADAs). Tofacitinib is an oral Janus Kinase (JAK) inhibitor that prevented ADA formation against iTox in preclinical studies.MethodsA phase 1 trial testing LMB-100 and tofacitinib in patients with MSLN-expressing cancers (pancreatic adenocarcinoma, n=13; cholangiocarcinoma, n=1; appendiceal carcinoma, n=1; cystadenocarcinoma, n=1) was performed to assess safety and to determine if tofacitinib impacted ADA formation. Participants were treated for up to 3 cycles with LMB-100 as a 30-minute infusion on days 4, 6, and 8 at two dose levels (100 and 140 µg/kg) while oral tofacitinib was administered for the first 10 days of the cycle (10 mg BID). Peripheral blood was collected for analysis of ADA levels, serum cytokines and circulating immune subsets.ResultsThe study was closed early due to occurrence of drug-induced pericarditis in 2 patients. Pericarditis with the combination was not reproducible in a transgenic murine model containing human MSLN. Two of 4 patients receiving all 3 cycles of treatment maintained effective LMB-100 levels, an unusual occurrence. Sustained increases in systemic IL-10 and TNF-α were seen, a phenomenon not observed in prior LMB-100 studies. A decrease in activated T cell subsets and an increase in circulating immunosuppressive myeloid populations occurred. No radiologic decreases in tumor volume were observed.DiscussionFurther testing of tofacitinib to prevent ADA formation is recommended in applicable non-malignant disease settings.Clinical trial registrationhttps://www.clinicaltrials.gov/study/NCT04034238.

Abstract Objective This study aimed to explore the efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with ZiLongJin Tablet (ZLJT) in delaying acquired resistance in advanced EGFR-mutant lung adenocarcinoma (LUAD) patients. Furthermore, we employed network pharmacology and molecular docking techniques to investigate the underlying mechanisms. Methods A retrospective comparative study was conducted on stage IIIc/IV LUAD patients treated with EGFR-TKIs alone or in combination with ZLJT at the Second Affiliated Hospital of the Air Force Medical University between January 1, 2017, and May 1, 2023. The study evaluated the onset of TKI resistance, adverse reaction rates, safety indicators (such as aspartate aminotransferase, alanine aminotransferase, and creatinine), and inflammatory markers (neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) to investigate the impact of EGFR-TKI combined with ZLJT on acquired resistance and prognostic indicators. Additionally, we utilized the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine, PubChem, UniProt, and Swiss Target Prediction databases to identify the active ingredients and targets of ZLJT. We obtained differentially expressed genes related to EGFR-TKI sensitivity and resistance from the Gene Expression Omnibus database using the GSE34228 dataset, which included sensitive (n = 26) and resistant (n = 26) PC9 cell lines. The "limma" package in R software was employed to detect DEGs. Based on this, we constructed a protein‒protein interaction network, performed gene ontology and KEGG enrichment analyses, and conducted pathway network analysis to elucidate the correlation between the active ingredients in ZLJT and signaling pathways. Finally, molecular docking was performed using AutoDockVina, PYMOL 2.2.0, and Discovery Studio Client v19.1.0 software to simulate spatial and energy matching during the recognition process between predicted targets and their corresponding compounds. Results (1) A total of 89 patients were included, with 40 patients in the EGFR-TKI combined with ZLJT group (combination group) and 49 patients in the EGFR-TKI alone group (monotherapy group). The baseline characteristics of the two groups were comparable. There was a significant difference in the onset of resistance between the combination group and the monotherapy group (P 0.05). There were no statistically significant differences in serum AST, ALT, CREA, TBIL, ALB and BUN levels between the two groups after medication (P > 0.05). (3) Regarding inflammatory markers, there were no statistically significant differences in the changes in neutrophil-to-lymphocyte Ratio(NLR) and Platelet-to-lymphocyte Ratio(PLR) values before and after treatment between the two groups (P > 0.05). (4) Network pharmacology analysis identified 112 active ingredients and 290 target genes for ZLJT. From the GEO database, 2035 differentially expressed genes related to resistant LUAD were selected, and 39 target genes were obtained by taking the intersection. A "ZLJT-compound-target-disease" network was successfully constructed using Cytoscape 3.7.0. GO enrichment analysis revealed that ZLJT mainly affected biological processes such as adenylate cyclase-modulating G protein-coupled receptor. In terms of cellular components, ZLJT was associated with the cell projection membrane. The molecular function primarily focused on protein heterodimerization activity. KEGG enrichment analysis indicated that ZLJT exerted its antitumor and anti-drug resistance effects through pathways such as the PI3K-Akt pathway. Molecular docking showed that luteolin had good binding activity with FOS (-9.8 kJ/mol), as did tanshinone IIA with FOS (-9.8 kJ/mol) and quercetin with FOS (-8.7 kJ/mol). Conclusion ZLJT has potential antitumor progression effects. For patients with EGFR gene-mutated non-small cell LUAD, combining ZLJT with EGFR-TKI treatment can delay the occurrence of acquired resistance. The underlying mechanisms may involve altering signal transduction pathways, blocking the tumor cell cycle, inhibiting tumor activity, enhancing cellular vitality, and improving the bioavailability of combination therapy. The combination of EGFR-TKI and ZLJT represents an effective approach for the treatment of tumors using both Chinese and Western medicine.

Abstract Glioblastoma (GBM) is an aggressive intracranial tumour, and current chemotherapy regimens have limited efficacy. Aloperine (ALO), a natural alkaline compound, has shown potential as an antitumor agent. However, the effect of ALO against GBM remains unclear. This study aimed to investigate the function of ALO in treating GBM. U87, A172, and GL261 cell lines were used for in vitro experiments, and GL261 was also used to establish in vivo models. The results showed that ALO inhibited the proliferation of GBM cells by cell cycle arrest and apoptosis. Furthermore, autophagy was found to play a critical role, suggested by observation of autophagosomes under the transmission electron microscopy. It was discovered for the first time that ALO targeted lysosomes directly in glioma cells, tested by fluo-rescence-labelled ALO and organelle-localizing probes. In addition, ALO inhibited late autophagy and induced paraptosis in GBM, verified by classical gene expression changes in qPCR and western blotting. Also, ALO inhibited tumour growth and acted synergistically with temozolomide in intracranial glioma mice models in vivo. Our findings suggest that ALO targets lysosomes to inhibit late autophagy in GBM, inducing cell cycle arrest, paraptosis, and apoptosis. ALO may therefore be a promising therapeutic agent for the treatment of GBM.

Using first-principles theory, this work purposes Ru-doped Janus WSSe (Ru-WSSe) monolayer as a potential gas sensor for detection of three typical gas species (CO, C2H2, and C2H4), in order to evaluate the operation status of the oil-immersed transformers. The Ru-doping behavior on the WSSe surface is analyzed, giving rise to the preferred doping site by the replacement of a Se atom with the formation energy of 0.01 eV. The gas adsorption of three gas species onto the Ru-WSSe monolayer is conducted, and chemisorption is identified for all three gas systems with the adsorption energy following the order: CO (−2.22 eV) > C2H2 (−2.01 eV) > C2H4 (−1.70 eV). Also, the modulated electronic properties and the frontier molecular orbital are investigated to uncover the sensing mechanism of Ru-WSSe monolayer upon three typical gases. Results reveal that the sensing responses of the Ru-WSSe monolayer, based on the variation of energy gap, to CO, C2H2, and C2H4 molecules are calculated to be 1.67 × 106, 2.10 × 105, and 9.61 × 103, respectively. Finally, the impact of the existence of O2 molecule for gas adsorption and sensing is also analyzed to uncover the potential of Ru-WSSe monolayer for practical application in the air atmosphere. The obtained high electrical responses manifest strong potential as a resistive sensor for detection of three gases. The findings hold practical implications for the development of novel gas sensing materials based on Janus WSSe monolayer. We anticipate that our results will inspire further research in this domain, particularly for applications in electrical engineering where the reliable detection of fault gases is paramount for maintaining the integrity and safety of power systems.

Moisture has been a crucial problem during the operation of cable systems. When we are faced with polypropylene (PP)-based insulation for the development of cable systems, there are few reports on the effects of water intrusion on the electrical performances of PP. In this study, the water absorption characteristics of isotactic PP (iPP) and atactic PP (aPP), as well as their effects on volume resistivity and relative permittivity, were investigated. The structure evolution during the water absorption process of the two PPs was also compared via infrared spectra and X-ray diffraction analyses. The results show that both of the two PPs show a saturation of water absorption at ~216 h, even though there are structural differences. And water intrusion into bulk could increase the interplanar spacing of iPP while decreasing the interplanar spacing of aPP. Moreover, with the increase in water absorption, the volume resistivity of the two PPs show a decreasing trend while the relative permittivity presents an increasing behavior, which shows an almost linear correlation.

The position error in an inertial navigation system (INS) for autonomous underwater vehicles (AUVs) increases over time. Terrain-aided navigation can assist in correcting these INS position errors. To enhance the matching accuracy under large initial position errors, an improved terrain matching algorithm comprising terrain contour matching (TERCOM), particle swarm optimization (PSO), and iterative closest contour point (ICCP), named TERCOM-PSO-ICCP, is proposed. Initially, an enhanced TERCOM with an increased rotation angle is utilized to minimize heading errors and reduce the initial position error. The similarity extremum approach evaluates the initial matching outcomes, leading to an enhanced accuracy in the initial results. Next, artificial bee colony (ABC)-optimized PSO is employed for secondary matching to further reduce the initial position error and narrow the matching area. Finally, the ICCP, using the Mahalanobis distance as the objective function, is applied for the third matching, leveraging the ICCP’s fine search capabilities. The effective combination of these three algorithms significantly improves the terrain-aided navigation matching effect. Two tests show that the improved TERCOM-PSO-ICCP effectively reduces the matching error and corrects the position of the INS.

With the increase in port throughput and the development of the trend of large-scale ships, selecting applicable anchor positions for ships and ensuring the rational and comprehensive utilization of anchorage areas have become a key issue in utilizing the rate of anchorage resources, ensuring the safety of ships anchoring operations and promoting the development of the shipping industry. Existing anchor position selection and detection algorithm studies are limited to a two-dimensional plane for ship anchor position selection, with few studies considering intelligent detection algorithms for safe ship anchoring water depths based on three-dimensional space, considering conditions such as wind and waves. By considering water depth conditions and the objectives of anchorage safety issues, this study proposes an intelligent detection method for ship anchor detection to find the ship’s ideal anchor location in the anchorages by applying the Monte Carlo algorithm. In the processing step, in combination with the Monte Carlo random plane anchor position detection algorithm and Monte Carlo random sampling water depth detection method, the anchor position circle radius model, safe spacing model, anchoring area detection model and safe water depth model are used for examining the anchorage area for awaiting the ship in three-dimensions. To verify the accuracy of the proposed model, based on the scale of common ship types and considering the most conservative parameters, a series of simulation experiments are conducted to check whether the water depth meets the requirements and fully ensure the safety of the experimental results. The research results indicate that the detection almost cover the whole anchorage area and obtain safe water depth restrictions. This method helps to improve the efficiency of ship anchoring and makes actual anchoring operations safer. Under the premise of ensuring sufficient safe spacing between ships, the anchorage ground can accommodate more ships and simulate multi-type ship anchor position detection operations concerning various ship-type parameters to further ensure the safety of ship anchoring.

In this article, a new intelligent fault-tolerant control (FTC) is designed to control a flexible-link manipulator with uncertain dead-zone and intermittent actuator faults. Initially, a smooth dead-zone inverse model using a hyperbolic tangent function is introduced to handle dead-zone nonlinearity and suppress input chattering. An adaptive law is proposed to estimate an unknown coupling item, combining the upper bounds of compensation error and floating bias faults, achieving robust adaptive control of the system. A new FTC strategy is subsequently developed to address intermittent actuator faults. Finally, the bounded convergence of system state errors is proven using direct Lyapunov methods, and the effectiveness and superiority of the proposed controller are demonstrated through numerical simulation and experiment.

Abstract Soybean whey and soybean hydrolyzate can be used for the biotechnological production of high-value products. Herein, we isolate soybean whey (SW)-and soybean hydrolyzate (SH)-derived bacterial cellulose (BC, produced by kombucha) and characterize it by a range of instrumental techniques to reveal differences in micromorphology, crystallinity, and themal behavior. Studies have shown that the amounts of wet state BC produced from HS, SW and SH was 181 g/L, 47 g/L and 83 g/L, respectively. The instrumental analysis of BC, included SEM, AFM, FT-IR, XRD and TGA. It is shown that the FT-IR spectra of BC have a similar character, but we found differences in the micromorphology,crystallinity and thermal temperature of BC. The minimum average widths of the fibers produced from SH medium was 100 ± 29 nm. The CrI values of BC produced from SH medium was 61.8%. The maximum thermal degradation rate temperature of BC produced from SW medium was 355.73 °C. The combined results demonstrate that soybean industrial waste can be used as a cost-effective raw material for BC production.

This research focused on the rubber bushings of the rear sub-frame in an electric vehicle. A dynamic model was developed to represent the bushing, incorporating an elastic element, a frictional element, and a viscoelastic element arranged in series using a fractional-order Maxwell and a Kelvin–Voigt model. To identify the parameters of the bushing model, an improved adaptive chaotic particle swarm optimization algorithm was employed, in conjunction with dynamic stiffness test data obtained at an amplitude of 0.2 mm. The test data obtained at different amplitudes (0.2 mm, 0.3 mm, 0.5 mm, and 1 mm) were fitted to the model, resulting in fitting errors of 1.13%, 4.07%, 4.42%, and 28.82%, respectively, when compared to the corresponding test data in order to enhance the accuracy of the model fitting; the Sobol sensitivity analysis method was utilized to analyze the parameter sensitivity of the model. Following the analysis, the parameters α, β, and k2, which exhibited high sensitivity, were re-identified. This re-identification process led to a reduction in the fitting error at the 1 mm amplitude to 7.45%. The improved accuracy of the model plays a crucial role in enhancing the simulation accuracy of design of experiments (DOE) analysis and verifying the vehicle’s performance under various conditions, taking into account the influence of the bushing.

Abstract This paper develops an adaptive neural fault‐tolerant control for an unknown two‐degree of freedom helicopter nonlinear system with output error constraints, actuator fault, and unknown external disturbances. A neural network disturbance observer is used to estimate system uncertainties and actuator gain failures. The tan‐type barrier Lyapunov equation is used to solve the system's output error constraint. To compensate for actuator bias failures and unknown external disturbances in the system, an adaptive auxiliary parameter is established. Furthermore, rigorously analyzing the chosen Lyapunov function, the system's stability is ensured. Finally, the numerical simulation results prove the rationality and effectiveness of the proposed control strategy.

Pseudoaneurysm is a rare but lethal complication of acute myocardial infarction. In this study, we present a unique case of a patient with left ventricular free wall rupture detected by cardiac magnetic resonance more than 1 year after a percutaneous transluminal coronary intervention.

Abstract The dual emission (DE) feature in materials holds great potential to revolutionize the development of one‐component system white organic light‐emitting diodes (WOLEDs). However, the reported DE materials remain scarce owing to the formidable challenge of breaking Kasha's rule and managing the intricate energy/charge transfer processes. Herein, we have introduced a groundbreaking DE AIEgen, 2CzAn‐TPE, which possesses a simple structure and undergoes Z‐to‐E isomerization and exhibits yellow and red fluorescence powders for pre‐ and post‐sublimation, respectively. With relatively lower potential energy, Z‐conformation ((Z)‐1,2‐diphenyl‐1,2‐bis(4‐(10‐(9‐phenyl‐9H‐carbazol‐3‐yl)anthracen‐9‐yl)phenyl)ethene) of 2CzAn‐TPE can be readily transformed into E‐conformation ((E)‐1,2‐diphenyl‐1,2‐bis(4‐(10‐(9‐phenyl‐9H‐carbazol‐3‐yl)anthracen‐9‐yl)phenyl)ethene) via vacuum sublimation. The utilization of X‐ray diffraction and grazing‐incidence‐wide‐angle X‐ray scattering techniques confirms the structural transformation, while the crystallographic analysis reveals the establishment of numerous intermolecular CH···π interactions between the tetraphenylethene (TPE) moiety and both the anthracene and carbazole units. This allows a densely packed molecular arrangement, thereby offering propitious conditions for excimer generation in the E‐conformation aggregated state. By utilizing the sublimated 2CzAn‐TPE as an emitter, a nondoped one‐component WOLED was prepared, exhibiting an exceptionally high external quantum efficiency (EQE) of 5.0%, which represents one of the highest performances among all one‐component WOLEDs. This research introduces a novel, simple, and efficient approach to realize highly efficient one‐molecule WOLEDs.

AbstractIntroduction Dysmagnesemia has been demonstrated to be involved in the pathophysiology of kidney diseases and is common in cardiac surgical patients. It remains unknown whether changes of serum magnesium after cardiac surgery affect AKI. We aimed to investigate the association of early postoperative magnesium with cardiac surgery-associated AKI in adults.Methods We conducted a multicenter retrospective cohort study involving patients who underwent cardiac surgery in the eICU Collaborative Research Database between 2014 and 2015. AKI within 7 days after surgery was defined using both serum creatinine and urine output criteria of Kidney Disease Improving Global Outcomes definition. Postoperative AKI was analyzed using multivariable logistic regression with early postoperative serum magnesium measured within the first 24 h after surgery as a continuous variable and categorically by quartiles.Results Postoperative AKI was identified in 3498 of 6124 (57.1%) patients receiving cardiac surgery. The median (25th–75th percentiles) early postoperative serum magnesium level of the study population was 2.3 (2.0–2.7) mg/dL. Higher serum magnesium level was associated with a higher risk of developing postoperative AKI (adjusted odds ratio (OR), 1.46 per 1 mg/dL increase; 95% confidence interval (CI), 1.31–1.62; p

Mycobacterium tuberculosis (Mtb) infection elicits both protein and lipid antigen-specific T cell responses. However, the incorporation of lipid antigens into subunit vaccine strategies and formulations has been underexplored, and the characteristics of vaccine-induced Mtb lipid-specific memory T cells have remained elusive. Mycolic acid (MA), a major lipid component of the Mtb cell wall, is presented by human CD1b molecules to unconventional T cell subsets. These MA-specific CD1b-restricted T cells have been detected in the blood and disease sites of Mtb-infected individuals, suggesting that MA is a promising lipid antigen for incorporation into multicomponent subunit vaccines. In this study, we utilized the enhanced stability of bicontinuous nanospheres (BCN) to efficiently encapsulate MA for in vivo delivery to MA-specific T cells, both alone and in combination with an immunodominant Mtb protein antigen (Ag85B). Pulmonary administration of MA-loaded BCN (MA-BCN) elicited MA-specific T cell responses in humanized CD1 transgenic mice. Simultaneous delivery of MA and Ag85B within BCN activated both MA- and Ag85B-specific T cells. Notably, pulmonary vaccination with MA-Ag85B-BCN resulted in the persistence of MA, but not Ag85B, within alveolar macrophages in the lung. Vaccination of MA-BCN through intravenous or subcutaneous route, or with attenuated Mtb likewise reproduced MA persistence. Moreover, MA-specific T cells in MA-BCN-vaccinated mice differentiated into a T follicular helper-like phenotype. Overall, the BCN platform allows for the dual encapsulation and in vivo activation of lipid and protein antigen-specific T cells and leads to persistent lipid depots that could offer long-lasting immune responses.

Abstract LMB‐100 is a novel immune‐conjugate (immunotoxin) that targets mesothelin. A phase 1/2 clinical trial was conducted (NCT02810418) with primary objectives assessing the safety and efficacy of LMB‐100 ± nab‐paclitaxel. Participant blood samples were analyzed for changes in serum cytokines and circulating immune cell subsets associated with response or toxicity. On Arm A, participants (n = 20) received standard 30‐minute LMB‐100 infusion with nab‐paclitaxel. Although clinical efficacy was observed, the combination caused intolerable capillary leak syndrome (CLS), a major toxicity of unclear etiology that affects many immunotoxin drugs. Participants developing CLS experienced rapid elevations in IFNγ and IL‐8 compared to those without significant CLS, along with midcycle increases in Ki‐67‐ CD4 T cells that were CD38, HLA‐DR, or TIM3 positive. Additionally, a strong increase in activated CD4 and CD8 T cells and a concurrent decrease in Tregs were seen in the single Arm A patient achieving a partial response. In Arm B, administration of single agent LMB‐100 to participants (n = 20) as a long infusion given over 24–48 h was investigated based on pre‐clinical data that this format could reduce CLS. An optimal dose and schedule of long infusion LMB‐100 were identified, but no clinical efficacy was observed even in patients receiving LMB‐100 in combination with nab‐paclitaxel. Despite this, both Arm A and B participants experienced increases in specific subsets of proliferating CD4 and CD8 T cells following Cycle 1 treatment. In summary, LMB‐100 treatment causes systemic immune activation. Inflammatory and immune changes that accompany drug associated CLS were characterized for the first time.

In intensive aquaculture systems, accurate water temperature prediction is crucial for aquaculture efficiency. Traditional prediction models often have limitations in dealing with strongly coupled, nonlinear, and time-varying water temperature data. A novel hybrid model for temperature prediction is proposed to improve prediction generalization ability and robustness. The model integrates advanced data processing and prediction techniques. Firstly, the VMD method is utilized to achieve effective data decomposition and noise reduction. Secondly, the CNN algorithm is applied to achieve feature extraction of the data. Finally, the bi-directional LSTM and self-concerned combination are used to obtain the final prediction results. The experimental results show that the MAE, RMSE, MSE, MAPE, and R2 of the VMD-CNN-BILSTM-SA combination prediction model proposed in this paper are 0.016, 0.143, 0.020, 0.035, and 0.978, respectively. Compared with other deep learning models, the BiLSTM model presented in this paper improves the R2 by 13.2% compared with LSTM and 13.7% over the GRU model. This study can be applied in fishery farming, which can reduce the risk of farming and promote the modernization of fishery.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used in the detection of brain disorders such as autism spectrum disorder based on various machine/deep learning techniques. Learning-based methods typically rely on functional connectivity networks (FCNs) derived from blood-oxygen-level-dependent time series of rs-fMRI data to capture interactions between brain regions-of-interest (ROIs). Graph neural networks have been recently used to extract fMRI features from graph-structured FCNs, but cannot effectively characterize spatiotemporal dynamics of FCNs, e.g., the functional connectivity of brain ROIs is dynamically changing in a short period of time. Also, many studies usually focus on single-scale topology of FCN, thereby ignoring the potential complementary topological information of FCN at different spatial resolutions. To this end, in this paper, we propose a multi-scale dynamic graph learning (MDGL) framework to capture multi-scale spatiotemporal dynamic representations of rs-fMRI data for automated brain disorder diagnosis. The MDGL framework consists of three major components: 1) multi-scale dynamic FCN construction using multiple brain atlases to model multi-scale topological information, 2) multi-scale dynamic graph representation learning to capture spatiotemporal information conveyed in fMRI data, and 3) multi-scale feature fusion and classification. Experimental results on two datasets show that MDGL outperforms several state-of-the-art methods.

Pigeon is a kind of poultry with high practicability and economic value, and humidity is an important indicator of the intensive breeding of pigeons, which is closely related to the healthy growth of pigeons. Humidity changes are complex, dynamic, and nonlinear. Accurately predicting humidity values and analyzing their changing trends is crucial to the growth of pigeons. Addressing low prediction accuracy and poor generalization of traditional humidity prediction methods, this paper proposes a combination based on partial least squares (PLS) data dimensionality reduction, Savitzky-Golay (SG) filter, and sparrow optimization algorithm (SSA) Predictive models to improve humidity forecast accuracy. First, the SG filter is used for data smoothing to remove abnormal noise in the data signal to enhance the feature learning ability of the prediction system. Next, the original data is selected through the PLS method to select information higher than the set threshold. Valuable information features are extracted for data dimensionality reduction. In addition, SSA is used to optimize key parameters and structure of the BiGRU model for improved prediction. Finally, a combined prediction model based on SG-PLS-SSA-BiGRU was built to simulate and predict the humidity of the pigeon house. The experimental results demonstrate the proposed model’s high accuracy and stability with minimal prediction error fluctuations, fast calculation speed, good feature extraction ability and generalization ability, and is very effective and reliable for predicting pigeon house breeding humidity.

Dissolved oxygen content is a key indicator of water quality in aquaculture environment. Because of its nonlinearity, dynamics, and complexity, which makes traditional methods face challenges in the accuracy and speed of dissolved oxygen content prediction. As a solution to these issues, this study introduces a hybrid model consisting of the Light Gradient Boosting Machine (LightGBM) and the Bidirectional Simple Recurrent Unit (BiSRU). Firstly, Linear interpolation and smoothing were used to identify significant parameters. LightGBM algorithm then determines the significance of dissolved oxygen by eliminating irrelevant variables and predicting dissolved oxygen in intensive aquaculture. Finally, the attention method was implemented to map the weighting and learning parameter matrices, so enabling the BiSRU’s hidden states to be assigned different weights. The findings shown that the presented prediction model can accurately anticipate the fluctuating trend of dissolved oxygen over a 10-day period in just 122 seconds, and the accuracy rate reached 96.28%. Comparing the model effects of LightGBM-BiSRU, LightGBM - GRU, LightGBM-LSTM, and BiSRU - Attention takes the least time. Its higher prediction accuracy can provide an essential reference for intensive aquaculture water quality regulation.

Abstract The pigeon food production industry from breeding to processing into food for market circulation involves many stages and people, which is prone to food safety issues and difficult to regulate. To address these problems, one possible solution is to establish a traceability system. However, in traditional traceability systems, a number of stages involved and each of them provides their own data accumulated in the database. Therefore, complex traceability data are compose of too many stages easily result in confusing information for customers. Besides, centralized data storage makes data vulnerable to be tampered with. To solve these problems, hazard analysis and critical control points (HACCP) principles have been utilized in our work which is a comprehensive traceability system. In this work, we analyze the pigeon food production industry through HACCP principles and determine some critical control points (CCPs), including incubation, breeding, transportation, slaughtering, processing, and logistics. With the help of these CCPs, we are able to build a traceability system with critical and abundant data but not too complicated for users. To further improve the system, there are different kinds of techniques integrated into it. Firstly, a permissioned blockchain, Hyperledger Fabric, is selected as blockchain module to enhance trustworthiness of data. Secondly, the system contains various IoT devices for automatically collecting environmental parameter data with the aim of reducing human interference. Besides, it is worth mentioning that the proposed information management device can decrease the data entry burden. Consequently, the implementation of the traceability system increase consumers’ confidence in pigeon food production. To summarize, it is a new application of modern agricultural information technique in food safety and a bold experiment in the field of poultry, particularly pigeons.

Context Lung cancer, the most common type of cancer, has a high mortality rate. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae plants, has antitumor effects. Objective We investigated the role of CuB on lung cancer and its potential mechanisms. Materials and methods A549 cells were treated with 0.1, 0.3, 0.6, and 0.9 μM CuB for 12, 24, and 48 h or untreated. Gene and protein levels were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Enzyme-linked immunosorbent assay (ELISA) detected inflammatory factors levels (TNF-α and IL-10). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and colony formation assays measured cell viability, apoptosis, and proliferation. The interaction between miR-let-7c and long non-coding RNA X inactive-specific transcript (XIST) or interleukin-6 (IL-6) was verified by dual-luciferase reporter assays. Results CuB treatment inhibited the proliferation of lung cancer cells and promoted cell apoptosis, and increased the expression of Bax and cleaved caspase3, decreased cyclin B1 and Bcl-2 expression. CuB suppressed XIST and IL-6 expression, and enhanced miR-let-7c expression. XIST silencing enhanced the inhibitory effect of CuB on cell proliferation and the promotion effect on apoptosis via upregulating miR-let-7c. Moreover, XIST targeted miR-let-7c to activate the IL-6/STAT axis. MiR-let-7c overexpression enhanced the regulatory effect of CuB on proliferation and apoptosis via suppressing the IL-6/STAT3 pathway. Discussion and conclusion CuB regulated cell proliferation and apoptosis by inhibiting the XIST/miR-let-7c/IL-6/STAT3 axis in lung cancer. These findings indicate CuB may have the possibility of clinical application in lung cancer treatment.

Abstract Soya bean sprout is a nutrient-abundant vegetable. However, enzymatic browning of soya bean sprouts during storage remains a challenge. In this study, the effects of treatment with MnCl2 or ZnCl2 on the browning index, antioxidant nutrient accumulation, total antioxidant capacity and enzyme activities of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) were investigated in soya bean sprouts after storage at 4 °C and 90% relative humidity for 0, 7, 14 and 21 days. The results showed that postharvest treatment with 1, 2 and 10 mM MnCl2 or ZnCl2 profoundly retarded enzymatic browning in soya bean sprouts to different extents. Compared with the control, the 10 mM MnCl2 and ZnCl2 treatments drastically enhanced ascorbic acid, total thiol and phenolic content, and enhanced FRAP (ferric-reducing ability of plasma) antioxidant capacity in stored soya bean sprouts. Moreover, the MnCl2 and ZnCl2 treatments enhanced SOD, CAT and PAL but decreased PPO and POD activities compared with the control. In addition, the Mn and Zn content in soya bean sprouts significantly increased, by approximately two- to threefold, compared with the control. This study provides a new method for improving the nutrient quality of soya bean sprouts based on postharvest Mn or Zn supplementation.

ObjectivesTo explore the effect of flipped classroom combined with case-based learning in Introduction to Environmental Health Science for the Master of Public Health (MPH).MethodsThe MPH Master’s class of 2022 was selected as the experimental group at Guilin Medical University from September to December 2022, and the flipped classroom combined with the case-based learning was adopted. The class of 2021 was the control group, and we taught them with the traditional teaching method. A self-designed questionnaire and academic performance were used to evaluate the teaching effects of the two groups.ResultsThere was no difference in the paper score between grades 2022 and 2021, and the design question score of grade 2022 was higher than that of grade 2021. The difference was statistically significant (p

Abstract Background Kidney stones have become a worldwide public health problem. The purpose of this research is to study the relationship between plasma cadmium level and the prevalence of kidney stones in an adult population. Methods The data of this study were based on a current survey conducted from December 2018 to November 2019 in Gongcheng Yao Autonomous County, Guangxi, China. A total of 940 study subjects of the same sex and age (within 2 years of each other) according to 1:1 matching were selected for a case–control study. The diagnosis of kidney stones was based on the presence of strong light spots, patches, clusters, or bands within the renal sinus region, followed by an echo-free bundle of acoustic images. Plasma metal elements were determined by the metal plasma method. The relationship between plasma cadmium concentration and the prevalence of kidney stones was assessed using logistic regression and restricted cubic spline regression. Results The crude ratio for kidney stones in the highest quartile of plasma cadmium was 1.164 (95% CI, 1.121 to 2.324) compared with the lowest quartile. A positive correlation was found between the two (P for trend = 0.039). After adjusting for potential confounders, the ratio of plasma cadmium to kidney stones in the highest quartile was 1.606 (95% CI, 1.100 to 2.344) compared with the lowest quartile, and the findings remained unchanged. Conclusion The odds of kidney stones in adults increased with increasing plasma cadmium exposure, and high plasma cadmium may be a risk factor for kidney stones.

Since 2013, a dengue epidemic has broken out in Yunnan, China and neighboring countries. However, after the COVID-19 pandemic in 2019, the number of dengue cases decreased significantly. In this retrospective study, epidemiological and genetic diversity characterizations of dengue viruses (DENV) isolated in Yunnan between 2017 and 2018 were performed. The results showed that the dengue outbreak in Yunnan from 2017 to 2018 was mainly caused by DENV1 (genotype I and genotype V) and DENV2 (Asia I, Asia II, and Cosmopolitan). Furthermore, correlation analysis indicated a significant positive correlation between the number of imported and local cases (correlation coefficient = 0.936). Multiple sequence alignment and phylogenetic divergence analysis revealed that the local isolates are closely related to the isolates from Myanmar and Laos. Interestingly, recombination analysis found that the DENV1 and DENV2 isolates in this study had widespread intra-serotype recombination. Taken together, the results of the epidemiological investigation imply that the dengue outbreak in Yunnan was primarily due to imported cases. This study provides a new reference for further investigations on the prevalence and molecular epidemiology of DENV in Yunnan, China.

Li-ion cathode active materials are transitioning from poly- to single-crystal structures. However, the performance of high Ni-content single-crystal cathodes remains below expectations. Here, via Al/Zr co-doping, the authors propose a strategy to mitigate structural degradation in this class of materials.

Since 2017, a fishing moratorium has been enforced in Lake Honghu as part of Chang–Jiang’s biodiversity conservation strategy. However, given that the lake is a semi-closed aquatic ecosystem and no longer serves as a habitat for certain fishes of the mid–lower Chang–Jiang basin, the efficacy of this moratorium remains uncertain. To address the question from a trophic ecology perspective, a stomach content analysis was performed on captured anchovies of C. brachygnathus, a current predominant species in Lake Honghu, from November 2020 to October 2021. The results showed that copepods, shrimps, and macrophytes were the main components of this anchovy’s diet, and there were size-related shifts in diets. The dominance of C. brachygnathus, a pelagic–littoral omnivore in this lake, implies a lacustrine environment shift triggered by continued human disturbances. The utilization of macrophytes as the main food items by large-sized anchovies of Lake Honghu has partially contributed to the rapid degradation of submerged vegetation. This highlights the need to remove large-sized individuals of C. brachygnathus and Carassius auratus, another benthic-omnivorous dominant fish, in order to effectively restore the aquatic vegetation and ecosystem of Lake Honghu. The current implementation of fishing moratoriums in subtropical shallow floodplain lakes such as Lake Honghu should be reviewed critically.