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Abstract Purpose This study aims to investigate whether adding fosaprepitant to palonosetron and dexamethasone is effective in preventing postoperative nausea and vomiting (PONV) in high-risk patients undergoing gynecologic surgery. Methods Eligible patients undergoing gynecological surgery were randomized into two groups (1:1). One group received fosaprepitant (150 mg) and the other (control) received a placebo infusion. Both groups received a single dose of palonosetron (0.25 mg) and dexamethasone (5 mg) together with therapeutic medication. The primary endpoint was the absence of vomiting and no use of rescue antiemetics during the first 24 h after surgery; complete response rate (CRR). Results CRR was significantly higher in the fosaprepitant group compared to the control group 0–24 h after surgery (P = 0.037; relative risk [RR], 1.116; 95% confidence interval [CI], 1.007 to 1.235). Moreover, CRR was also significantly higher during the 24–48 h (P = 0.004; RR, 1.148; 95% CI, 1.045 to 1.261) and 48–72 h (P = 0.039; RR, 1.083; 95% CI, 1.005 to 1.168) observation periods respectively. The complete control rate was higher in the fosaprepitant group than in the control group during the 0–24 h observation period (P = 0.012; RR, 1.367; 95% CI, 1.067 to 1.751). Nausea and rescue antiemetic use were comparable between the two groups. The severity of vomiting was significantly higher in the fosaprepitant group than in the control group on the second day (P = 0.016). Dynamic pain visual analog scale score was lower in the fosaprepitant group and quality of recovery-15 scores were significantly higher in the same group during 0–24 h observation period (P = 0.018 and 0.005, respectively). Conclusions The triple combination of fosaprepitant, palonosetron, and dexamethasone was superior in the prevention of PONV after gynecologic surgery in high-risk patients. We suggest that for high-risk patients, a triple combination therapy may be a better choice. Trial registration Registered at the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=171741 ) with No. ChiCTR2200060890 on June 13, 2022. Principal investigator: Jingdun Xie.

Abstract GLS4 is a first‐in‐class hepatitis B virus (HBV) capsid assembly modulator (class I) that is co‐administered with ritonavir to maintain the anticipated concentration required for the effective antiviral activity of GLS4. In this study, the first physiologically‐based pharmacokinetic (PBPK) model for GLS4/ritonavir was successfully developed. The predictive performance of the PBPK model was verified using data from 39 clinical studies, including single‐dose, multiple‐dose, food effects, and drug–drug interactions (DDI). The PBPK model accurately described the PK profiles of GLS4 and ritonavir, with predicted values closely aligning with observed data. Based on the verified GLS4/ritonavir model, it prospectively predicts the effect of hepatic impairment (HI) and DDI on its pharmacokinetics (PK). Notably, CYP3A4 inducers significantly influenced GLS4 exposure when co‐administered with ritonavir; co‐administered GLS4 and ritonavir significantly influenced the exposure of CYP3A4 substrates. Additionally, with the severity of HI increased, there was a corresponding increase in the exposure to GLS4 when co‐administered with ritonavir. The GLS4/ritonavir PBPK model can potentially be used as an alternative to clinical studies or guide the design of clinical trial protocols.

In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound 14–3 has an IC50 of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, 14–3 induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that 14–3 is less toxic than 5-Fu with no obvious toxicity. These results suggest that 14–3 is a potential candidate for the development of anti-tumor drugs.

Abstract Whether the anesthesia technique, inhalational general anesthesia (IGA) or propofol-based anesthesia (PBA), influences the long-term survival of non-metastatic breast cancer (eBC) remain unclear and controversial. We carried out a literature search on 16thJuly, 2022 for studies comparing IGA and PBA in eBC undergoing standard surgery, according to PRISMA 2020. The major endpoint in our study was overall survival (OS). Seventeen studies including four randomized clinical trials and thirteen retrospective cohort studies were included in the meta-analysis. Ten studies provided data for crude OS in unweighted eBC patients (imbalance in baseline characteristics). The summarized estimate HRs of the PBA group versus the IGA group (ten studies, N = 127,774, IGA group: 92,592, PBA group: 35,182.) was 0.83 (95%CI: 0.78–0.89). Compared with IGA, PBA was associated with both better 1-year OS (two studies, N = 104,083, IGA group: 84,074, PBA group: 20,009. Pooled HR = 0.80, 0.73–0.89) and 5-year OS (six studies, N = 121,580, IGA group: 89,472, PBA group: 32,108. HR = 0.80, 0.74–0.87). Ten studies applied PSM method to balance the baseline characteristics. In these weighted patients, PBA still showed a better OS (ten studies, N = 105,459, IGA group: 79,095, PBA group: 26,364. HR = 0.93, 0.87–1.00), a better 1-year OS (two studies, N = 83,007, IGA group: 67,609, PBA group: 15,398. HR = 0.88, 0.78–0.98) and a trend towards a better 5-year OS (nine studies, N = 121,580, IGA group: 76,797, PBA group: 24,066. HR = 0.95, 0.88–1.03). Loco-regional recurrence-free survival (LRRFS) was also better in PBA group (HR = 0.73, 0.61–0.86). The present study is the first comprehensive meta-analysis to demonstrate that propofol-based anesthesia could significantly improve OS and LRRFS in non-metastatic breast cancer patients, compared with inhalational anesthesia.

Camellia fascicularis has important ornamental, medicinal, and food value. It also has tremendous potential for exploiting bioactivities. However, the bioactivities of secondary metabolites in C. fascicularis have not been reported. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 15 compounds were identified, including 5 flavonoids (1–5), a galactosylglycerol derivative (6), a terpenoid (7), 4 lignans (8–11), and 4 phenolic acids (12–15). Compounds 6–7 and 9–12 were isolated from the genus Camellia for the first time. The remaining compounds were also isolated from C. fascicularis for the first time. Evaluation of antioxidant and antimicrobial activities revealed that compounds 5 and 8–11 exhibited stronger antioxidant activity than the positive drug ascorbic acid, while compounds 7, 13, and 15 showed similar activity to ascorbic acid. The minimum inhibitory concentration (MIC) of antibacterial activity for compounds 5, 7, 9, 11, and 13 against Pseudomonas aeruginosa was comparable to that of the positive control drug tetracycline at a concentration of 62.50 µg/mL; other secondary metabolites inhibited Escherichia coli and Staphylococcus aureus at concentrations ranging from 125–250 µg/mL.

Abstract Cancer cells generally exhibit ‘iron addiction’ phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from Phyllanthus acidus (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic ‘ballooning’ phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death. Graphical Abstract

Hyperlipidemia is a prevalent chronic metabolic disease that severely affects human health. Currently, commonly used clinical therapeutic drugs are prone to drug dependence and toxic side effects. Dietary intervention for treating chronic metabolic diseases has received widespread attention. Rosa sterilis is a characteristic fruit tree in China whose fruits are rich in flavonoids, which have been shown to have a therapeutic effect on hyperlipidemia; however, their exact molecular mechanism of action remains unclear. Therefore, this study aimed to investigate the therapeutic effects of R. sterilis total flavonoid extract (RS) on hyperlipidemia and its possible mechanisms. A hyperlipidemic zebrafish model was established using egg yolk powder and then treated with RS to observe changes in the integral optical density in the tail vessels. Network pharmacology and molecular docking were used to investigate the potential mechanism of action of RS for the treatment of hyperlipidemia. The results showed that RS exhibited favorable hypolipidemic effects on zebrafish in the concentration range of 3.0–30.0 μg/mL in a dose-dependent manner. Topological and molecular docking analyses identified HSP90AA1, PPARA, and MMP9 as key targets for hypolipidemic effects, which were exerted mainly through lipolytic regulation of adipocytes and lipids; pathway analysis revealed enrichment in atherosclerosis, chemical carcinogenic-receptor activation pathways in cancers, and proteoglycans in prostate cancer and other cancers. Mover, chinensinaphthol possessed higher content and better target binding ability, which suggested that chinensinaphthol might be an important component of RS with hypolipidemic active function. These findings provide a direction for further research on RS interventions for the treatment of hyperlipidemia.

IntroductionIntestinal dysfunction poses a severe problem by preventing the digestion and absorption of nutrients. The gut, being the most vital organ for these processes, plays a crucial role in ensuring our body receives the nutrients it needs. We explored the mitigating effect of Morchella esculenta polysaccharides (MEP) on intestinal injury induced by lipopolysaccharides (LPS) through the modulation of intestinal flora.MethodsFor this purpose, Kunming mice (KM) were divided into three groups, namely, PC, PM, and PY. Group PY was treated with MEP, while groups PM and PY were induced with LPS.ResultsThe results showed that weight loss in the PM group was significantly greater than that in the PY group (P < 0.05), and the organ indexes of the lung and spleen in the PM group were significantly higher than those in the PC (P < 0.01) and PY (P < 0.05) groups. LPS caused severe injuries in KM mice in the PM group, characterized by broken villi. However, MEP treatment could alleviate this damage in the PY group, resulting in relatively intact villi. The serum analysis showed that tumor necrosis factor alpha (TNF-ɑ) (P < 0.01), interleukin 6 (IL-6) (P < 0.01), and 3,4-methylenedioxyamphetamine (MDA) (P < 0.05) levels were significantly higher in the PM group, while IL-10 (P < 0.001), superoxide dismutase (SOD) (P < 0.01) and glutathione peroxidase (GSH-Px) (P < 0.01) were significantly lower in that group. Interestingly, supplementation with MEP could lower the levels of TNF-ɑ, IL-10, IL-6, MDA while increasing the levels of superoxide dismutase (SOD) (P < 0.01) and GSH-Px. The gut microbiota analysis yielded 630,323 raw reads and 554,062 clean reads, identifying 3,390 amplicon sequencing variants (ASVs). One phylum and five genera were notably different among animal groups, including Escherichia_Shigella, Limosilactobacillus, unclassified_Geminicoccaceae, unclassified_Rhodobacteraceae, and Parabacteroides (P. distasonis).DiscussionIn conclusion, we found that MEP could mitigate the intestinal damage caused by LPS by modulating the inflammatory response, oxidative resistance, and intestinal flora of KM mice. Our results may provide insights into novel treatment options for intestine-related diseases.

Abstract Mapping grazing intensity (GI) using satellites is crucial for developing adaptive utilization strategies according to grassland conditions. Here we developed a monitoring framework based on a paired sampling strategy and the classification probability of random forest algorithm to produce annual grazing probability (GP) and GI maps at 10-m spatial resolution from 2015 to 2021 for the largest temperate meadow in China (Hulun Buir grasslands), by harmonized Landsat 7/8 and Sentinel-2 images. The GP maps used values of 0–1 to present detailed grazing gradient information. To match widely used grazing gradients, annual GI maps with ungrazed, moderately grazed, and heavily grazed levels were generated from the GP dataset with a decision tree. The GI maps for 2015–2021 had an overall accuracy of more than 0.97 having significant correlations with the statistical data at city (r = 0.51) and county (r = 0.75) scales. They also effectively captured the GI gradients at site scale (r = 0.94). Our study proposed a monitoring approach and presented annual 10-m grazing information maps for sustainable grassland management.

Extreme rainfalls could greatly affect operations of urban rail transit systems of mountainous cities, which are prone to have landslides and floods under rainfalls. Therefore, it is essential to assess and enhance the resilience of mountainous urban rail transit networks under heavy rainfalls. Taking the metro network of Chongqing, the largest mountainous city in China, as an example, this study establishes a network topology model to identify the high-risk nodes under rainfalls and find the effective recovery strategies. By introducing the metro ridership and topological shortest distances, a network service efficiency function is developed, and the importance of nodes is quantified using service efficiency index and topological importance index. The resilience assessment model based on service efficiency is constructed using the resilience triangle theory. Additionally, risk levels for landslide and flood-prone areas are classified using the K-means algorithm, based on rainfall, elevation, and slope data, identifying high-risk stations. Finally, the node recovery sequence and strategies for high-risk nodes affected by landslides and floods are examined. The results indicate that in extreme rainfall scenarios, two transfer stations (Daping and Fuhua Road) are among the high-risk landslide stations, while most other nodes have a service efficiency index of less than 0.2. High-risk flood stations are located on non-transfer lines and mostly on metro lines with high traffic flow, with service efficiency index generally high, with some stations, like Bijin Station, exceeding 0.3. When all affected nodes fail, network service efficiency decreases by 84.0% and 75.2% under landslide and flood disasters, respectively. Compared with the random recovery strategy, recovery strategies based on topological importance and service efficiency index, the optimal recovery strategy based on genetic algorithm performs much better.

Crop monitoring can promptly reflect the growth status of crops. However, conventional methods of growth monitoring, although simple and direct, have limitations such as destructive sampling, reliance on human experience, and slow detection speed. This study estimated the fresh weight of lettuce (Lactuca sativa L.) in a plant factory with artificial light based on three-dimensional (3D) reconstruction technology. Data from different growth stages of lettuce were collected as the training dataset, while data from different plant forms of lettuce were used as the validation dataset. The partial least squares regression (PLSR) method was utilized for modeling, and K-fold cross-validation was performed to evaluate the model. The testing dataset of this model achieved a coefficient of determination (R2) of 0.9693, with root mean square error (RMSE) and mean absolute error (MAE) values of 3.3599 and 2.5232, respectively. Based on the performance of the validation set, an adaptation was made to develop a fresh weight estimation model for lettuce under far-red light conditions. To simplify the estimation model, reduce estimation costs, enhance estimation efficiency, and improve the lettuce growth monitoring method in plant factories, the plant height and canopy width data of lettuce were extracted to estimate the fresh weight of lettuce in addition. The testing dataset of the new model achieved an R2 value of 0.8970, with RMSE and MAE values of 3.1206 and 2.4576.

Autonomous berthing is a critical phase in the fully autonomous navigation process of MASS (Maritime Autonomous Surface Ship). However, the autonomous berthing stage of MASS is significantly influenced by environmental factors and involves a wide range of technical fields, making the technology not yet fully mature. Therefore, this paper addresses three key technological challenges related to ship path planning, guidance and motion control, as well as position and state perception. Additionally, it explores the decision-making and control system architecture for autonomous berthing of MASS. An effective autonomous berthing solution for MASS is proposed. Based on vessel berthing maneuvering, a decision-making algorithm for autonomous berthing is designed. The A-star algorithm is optimized, and an expected path for unmanned boat experiments is designed offline using this algorithm. Subsequently, an indirect ship guidance and motion control program is proposed based on a CFDL-MFAC (Compact Form Dynamic Linearization based Model-Free Adaptive Control) algorithm. Experimental results show that the proposed autonomous berthing decision-making and control system architecture can effectively assist the unmanned boat in achieving autonomous berthing and help it to berth in a stable and desirable state.

Camellia fascicularis is a valuable ornamental, edible, and medicinal plant with promising prospects for bioactivity development. We screened the bioactivity of eight fractions (Fr. A−I) obtained from the ethyl acetate phase of C. fascicularis via silica gel column chromatography. The results indicated that the anti-inflammatory, antioxidative, and antimicrobial active components were mainly found in Fr. B*, E, A, and H; Fr. A–G; and Fr. D–I, respectively. Bioactivity-guided isolation identified 18 secondary metabolites. Compounds 1, 3–5, 7, and 15–18 were isolated from the genus Camellia for the first time in this study, whereas the other compounds were also isolated from this plant for the first time. The structures of these compounds were elucidated through comprehensive spectroscopic techniques. Compounds 1, 9−11, 28, 30, and 31 demonstrated antioxidative activities comparable to those of ascorbic acid, whereas the remaining compounds exhibited diminished antioxidative activity. In terms of antimicrobial activity, compounds 7, 18, 22, and 27 exerted inhibitory potency against Pseudomonas aeruginosa, similar to tetracycline (MIC: 125 µg/mL). Other compounds showed moderate to weak inhibitory effects against Staphylococcus aureus and Escherichia coli (MIC: 250–500 µg/mL). Molecular docking revealed that compounds 2, 36, 41, and 65 showed strong binding affinity for 8ET0, whereas compounds 2, 36, 38, 40, 63, and 65 showed strong binding affinity for 3A4A. This research further increased the diversity of the secondary metabolites of C. fascicularis, laying a foundation for the subsequent development and utilization of this species.

To investigate the genetic basis of processing quality- and yield-related traits in bread wheat (Triticum aestivum L., AABBDD), a systematic analysis of wheat processing quality- and yield-related traits based on genome-wide association studies (GWASs) of 285 regional test lines of wheat from Hebei province, China, was conducted. A total of 87 quantitative trait loci (QTL), including twenty-one for water absorption (WA), four for wet gluten content, eight for grain protein content, seventeen for dough stability time (DST), thirteen for extension area (EA), twelve for maximum resistance (MR), five for thousand-grain weight (TGW), one for grain length, and six for grain width were identified. These QTL harbored 188 significant single-nucleotide polymorphisms (SNPs). Twenty-five SNPs were simultaneously associated with multiple traits. Notably, the SNP AX-111015470 on chromosome 1A was associated with DST, EA, and MR. SNPs AX-111917292 and AX-109124553 on chromosome 5D were associated with wheat WA and TGW. Most processing quality-related QTL and seven grain yield-related QTL identified in this study were newly discovered. Among the surveyed accessions, 18 rare superior alleles were identified. This study identified significant QTL associated with quality-related and yield-related traits in wheat, and some of them showed pleiotropic effects. This study will facilitate molecular designs that seek to achieve synergistic improvements of wheat quality and yield.

Abstract A growing body of evidence suggests that the histone demethylase-lysine demethylase 5 (KDM5) family is associated with drug resistance in cancer cells. However, it is still not clear whether KDM5 family members promote chemotherapy resistance in pancreatic ductal adenocarcinomas (PDAC). Comprehensive bioinformatics analysis was performed to investigate the prognostic value, and functional mechanisms of KDM5 family members in PDAC. The effects of KDM5 family members on drug resistance in PDAC cells and the relationship with CD44, as a stem cell marker, were explored by gene knockout and overexpression strategies. Finally, our findings were validated by functional experiments such as cell viability, colony formation and invasion assays. We found that the expression of KDM5A/C was significantly higher in gemcitabine-resistant cells than in sensitive cells, consistent with the analysis of the GSCALite database. The knockdown of KDM5A/C in PDAC cells resulted in diminished drug resistance, less cell colonies and reduced invasiveness, while KDM5A/C overexpression showed the opposite effect. Of note, the expression of KDM5A/C changed accordingly with the knockdown of CD44. In addition, members of the KDM5 family function in a variety of oncogenic pathways, including PI3K/AKT and Epithelial-Mesenchymal Transition. In conclusion, KDM5 family members play an important role in drug resistance and may serve as new biomarkers or potential therapeutic targets in PDAC patients.

Enhancing the spatial and temporal coordination between soil water and roots is very important for crop growth. The vertical distribution and relationship between soil water and root are however poorly understood during maize growth under different soil water conditions. In this study, two maize hybrids ZD958 and FM985 were treated with drip irrigation (DI), flood irrigation (FI), and rainfed (RF) in two–year field experiment as well as with irrigation at 0–30 (TI), 30–60 (MI), 60–90 (BI), 0–90 cm soil layers (AI) and no irrigation in three–year tube experiment. In field experiment, DI and FI both increased root dry weight, root length density (RLD), and the proportion of coarse root length at different soil layers relative to RF. DI increased grain yield by 10.0% in FM985 and by 10.8% in ZD958 compared with FI. Both total root and fine root length were greater in DI than in FI, which increased the nitrogen and water use efficiency and yield. In the tube experiment, irrigation at different soil layers increased root dry weight, RLD and the proportion of coarse root length compared with no irrigation, with AI increasing the most. FM985 distributed more roots at the 0–30 cm soil layer than ZD958. Grain yields were positively correlated with the RLD in each soil layer and coarse root proportion at the upper layer (r=0.493** in field experiment and r=426** in tube experiment) but negatively correlated with root–shoot ratio (r=−0.793** in field experiment and r=−670** in tube experiment) at maturity stage. In conclusion, there is a large potential to improve maize yield by enhancing the spatial coordination between root distribution and soil water movement.

IntroductionAcupuncture analgesia (AA) is widely used in clinical practice. The autonomic nervous system (ANS) may be an important pathway for acupuncture signal transduction. However, real-time changes in autonomic function during AA and the effect of “needle sensation” remain unclear.MethodsWe established a human pain model in healthy adults and randomly assigned 128 participants to the model, sham acupuncture, and acupuncture groups in a 1:1:2 ratio. Heart rate variability (HRV), including total power (TP), low-frequency power (LF), high-frequency power (HF), ratio of LF to HF (LF/HF), standard deviation of the normal-normal intervals (SDNN), and root mean square of successive interval differences (RMSSD), were used to assess autonomic function. The visual analog scale (VAS) and efficiency were used to assess the analgesic effect of acupuncture. The Massachusetts General Hospital acupuncture sensation scale (MASS) was used to indicate the intensity of the needle sensation. Anxiety levels were also measured. Finally, the correlation of MASS with HRV, VAS, and anxiety levels was analyzed.ResultsVAS decreased after 10 min of needling and 5 min after needle withdrawal in the acupuncture group compared with those in the model group (p = 0.038, p = 0.020). The efficacy rates were 82.0, 50.0, and 61.3% in the acupuncture, model, and sham groups, respectively. These represent significant differences between the acupuncture group and the model and sham acupuncture groups (p

Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.

Abstract Aversion refers to feelings of strong dislike or avoidance toward particular stimuli or situations. Aversion can be caused by pain stimuli and has a long-term negative impact on physical and mental health. Aversion can also be caused by drug abuse withdrawal, resulting in people with substance use disorder to relapse. However, the mechanisms underlying aversion remain unclear. The ventrolateral periaqueductal gray (vlPAG) is considered to play a key role in aversive behavior. Our study showed that inhibition of vlPAG GABAergic neurons significantly attenuated the conditioned place aversion (CPA) induced by hindpaw pain pinch or naloxone-precipitated morphine withdrawal. However, activating or inhibiting glutamatergic neurons, or activating GABAergic neurons cannot affect or alter CPA response. AKAP150 protein expression and phosphorylated TRPV1 (p-TRPV1) were significantly upregulated in these two CPA models. In AKAP150flox/flox mice and C57/B6J wild-type mice, cell-type-selective inhibition of AKAP150 in GABAergic neurons in the vlPAG attenuated aversion. However, downregulating AKAP150 in glutamatergic neurons did not attenuate aversion. Knockdown of AKAP150 in GABAergic neurons effectively reversed the p-TRPV1 upregulation in these two CPA models utilized in our study. Collectively, inhibition of the AKAP150/p-TRPV1 pathway in GABAergic neurons in the vlPAG may be considered a potential therapeutic target for the CPA response.

To investigate the chemical constituents of Diaporthe tectonigena, a predominant endophytic fungus in the ancient tea tree of Camellia taliensis, the rice solid-state fermentation extract was isolated and purified by silica gel, Diaion HP20 and Sephadex LH-20 column chromatographies, and the chemical structures were elucidated by extensive HRMS, 1H-NMR, 13C-NMR, HSQC, HMBC and COSY spectroscopic analyses. The results were as follows: (1) Four compounds were isolated from the rice solid-state fermentation extract of Diaporthe tectonigena, including a new tetrahydro-β-carboline diketopiperazine alkaloid named tectonicgenazine A (1). (2) Three known compounds, trans-cyclo-(D-tryptophanyl-L-tyrosyl) (2), 1H-indole-3-carboxylic acid-2,3-dihydroxypropyl ester (3) and N-hydroxyethyl-2-acetylpyrrole (4) were obtained and identified, and Compound 3 was isolated from nature for the first time.

In order to provide a scientific basis for optimum harvest time, the nutrient changes of avocado (Persea americana) fruit during the growth and development were studied. An approach of inductively coupled plasma atomic emission spectrometry, ion exchange chromatography derived after ninhydrin column, reflux extraction, burning and GC-MS technique were applied to determine the contents of mineral elements, ash, amino acids, crude fat, and fatty acid composition in three avocado cultivars (‘HASS’‘V3’ and ‘V4’), at different growth and development time from June to December. The results were as follows: (1) Oleic acid was the main oil component in the three avocado cultivars. The contents of crude fat in ‘HASS’ and ‘V4’ fruits increased continuously during the growth and development stages, and reached to the maximum on December, while V3 fruit increased continuously from June to October, while decreased in November and December. (2) All fruits of ‘HASS’‘V3’ and ‘V4’ contained 17 kinds of amino acids, including seven essential (Thr, Met, Val, Leu, Ile, Phe, Lys) for human beings, two essential (Arg, His) for children, and eight non-essential (Pro, Tyr, Cys, Ala, Gly, Glu, Ser, Asp) amino acids. The contents of 17 amino acids in ‘HASS’ and ‘V3’ fruits reached to the peak in November, while ‘V4’ fruits reached to the peak in October. (3) All the ‘HASS’‘V3’ and ‘V4’ fruits contained nine mineral elements of P, K, Ca, Mg, Zn, Fe, Mn, Cu and Na. Among which, the contents of P, K, Zn, Fe and Na accumulated to the maximum in the later stages of growth (October to December), while the changes for the other four mineral elements were not obvious. (4) The variation of ash contents in the three avocado cultivars was similar to that of the crude fat. In conclusion, It suggests that the three studied avocado cultivars, ‘HASS’‘V3’ and ‘V4’, have met the picking requirements since October and can be optimized the harvest time following fluctuations in demand. The results provide a scientific basis for determining the best time to harvest avocados.

Camellia fascicularis has important ornamental, medicinal, and food values, which also have tremendous potential for exploiting bioactivities. We performed the bioactivity-guided (antioxidant and antimicrobial) screening of eight fractions obtained from the ethyl acetate phase of C. fascicularis. The antioxidant activity was measured by DPPH, ABTS, and FRAP, and the antibacterial activity was measured by the minimum inhibitory concentration (MIC) of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. The results of bioactivity-guided isolation indicated that the major antioxidant compounds in the ethanolic extracts of C. fascicularis may be present in fractions (Fr.) (A–G, obtained after silica gel column chromatography). Fr. (D–I, obtained after silica gel column chromatography) is a fraction of C. fascicularis with antimicrobial activity. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 17 compounds were identified, including four phenolics (1, 3–4, and 14), a phenylpropane (2), five terpenoids (5–7, 12, and 15), four flavonoids and flavonoid glycosides (8–10 and 16), and two lignins (13 and 17). Compounds 4–7, 13–15, and 17 were isolated from the genus Camellia for first time. The remaining compounds were also isolated from C. fascicularis for first time. The evaluation of antioxidant and antimicrobial activities revealed that compounds 1, 3, 9, 11, and 17 exhibited higher antioxidant activity than the positive control drug (ascorbic acid), and compounds 4, 8, 10, and 13 showed similar activity to ascorbic acid. The other compounds had weaker or no significant antioxidant activities. The MIC of antibacterial activity for compounds 4, 7, and 11–13 against P. aeruginosa was comparable to that of the positive control drug tetracycline at 125 µg/mL, and other secondary metabolites inhibited E. coli and S. aureus at 250–500 µg/mL. This is also the first report of antioxidant and antimicrobial activities of compounds 5–7, 13–15, and 17. The results of the study enriched the variety of secondary metabolites of C. fascicularis and laid the foundation for further research on the pharmacological efficacy and biological activity of this plant.

The fruit of Choerospondias axillaris (Anacardiaceae), known as south wild jujube in China, has been consumed widely in several regions of the world to produce fruit pastille and leathers, juice, jam, and candy. A comprehensive chemical study on the fresh fruits led to the isolation and identification of 18 compounds, including 7 new (1–7) and 11 known (8–18) comprised of 5 alkenyl (cyclohexenols and cyclohexenones) derivatives (1–5), 3 benzofuran derivatives (6–8), 6 flavonoids (9–14) and 4 lignans (15–18). Their structures were elucidated by extensive spectroscopic analysis. The known lignans 15–18 were isolated from the genus Choerospondias for the first time. Most of the isolates exhibited significant inhibitory activity on α-glucosidase with IC50 values from 2.26 ± 0.06 to 43.9 ± 0.96 μM. Molecular docking experiments strongly supported the potent α-glucosidase inhibitory activity. The results indicated that C. axillaris fruits could be an excellent source of functional foods that acquire potential hypoglycemic bioactive components.

Summary: Dopamine D1 receptor-expressing medium spiny neurons (D1R-MSNs) and dopamine D2 receptor-expressing MSNs (D2R-MSNs) in nucleus accumbens (NAc) have been demonstrated to show different effects on reward and memory of abstinence. A-kinase anchoring protein 150 (AKAP150) expression in NAc is significantly upregulated and contributes to the morphine withdrawal behavior. However, the underlying mechanism of AKAP150 under opioid withdrawal remains unclear. In this study, AKAP150 expression in NAc is upregulated in naloxone-precipitated morphine withdrawal model, and knockdown of AKAP150 alleviates morphine withdrawal somatic signs and improves the performance of conditioned place aversion (CPA) test. AKAP150 in NAc D1R-MSNs is related to modulation of the performance of morphine withdrawal CPA test, while AKAP150 in NAc D2R-MSNs is relevant to the severity of somatic responses. Our results suggest that AKAP150 from D1R-MSNs or D2R-MSNs in NAc contributes to the developmental process of morphine withdrawal but plays different roles in aspects of behavior or psychology.

To provide reference for the safety consumption of Phyllanthus acidus (PA) as food and its further medicinal development and utilization, a comparative study on acute and short-termtoxicity and α-glucosidase inhibitory ability of different components of its branches and leaves was conducted. The crude extract of PA, prepared under aqueous ethanol reflux extraction, was partitioned successively with petroleum ether, ethyl acetate and N-butanol according to the polarity. Furthermore, an alcohol-eluted and water-eluted fractions were obtained from water-soluble residue by column chromatography. The half inhibitory concentration (IC50) of α-glucosidase was used as the evaluation index to compare the in vitro hypoglycemic activity of different extracts. The acute toxicity of these fractions was screened by maximum tolerated dose (MTD), median lethal dose (LD50) values, and their subacute toxicity was evaluated by continuous oral administration of samples for 20 days. The results showed that each component of PA had a certain inhibitory ability to α-glucosidase. The MTD of crude extract of PA was 2.0 g/kg, and the order of acute toxicity for different fractions was ethanol-eluted fraction>water-eluted fraction>petroleum ether fraction>ethyl acetate fraction>N-butanol fraction>crude extract. The main acute toxicity symptoms were startle followed by idling, writhing, and shortness of breath. Subacute toxicity test showed no obvious toxicity and lesions. It was indicated that it was safe to take 2 g/kg/d (equivalent to 8.6 g/kg of dried branches and leaves) of the whole component of PA at oral ingestion. Thus, they have the potential to be developed as hypoglycemic, weight-loss food and medicine.

Abstract Aims To establish a sensitive, scientific and practical evaluation system for haemodialysis nursing and to provide a reference for the evaluation of haemodialysis nursing quality. Design Through a literature review and Delphi method. Method According to the literature review, a preliminary nursing‐sensitive quality indicators for haemodialysis were established, and an expert survey questionnaire was designed. Finally, the evaluation system for the nursing‐sensitive quality indicators was determined using the Delphi method. Results Thirteen nursing‐sensitive quality indicators for haemodialysis were finally constructed, including two structural indicators, three process indicators and eight outcome indicators. The effective recovery rate of the two rounds of expert survey questionnaires was 100%, the coefficient of judgement basis is 0.956, the coefficient of familiarity is 0.833, the coefficient of authority is 0.895, and the Kendall's harmony coefficients of the two rounds of expert consultation were 0.158 ~ 0.307 and 0.170 ~ 0.315, respectively, with statistical significance (p

Based on combing the concept and development of intelligent ship, this paper brings forward the summary and classification of intelligent ships proposed by different institutions, and the main classification schemes are compared accordingly. Then one of these classification schemes is selected to study what are the key navigational risks under each grading level, with a detailed analysis of these risk factors. Finally, the index system of navigational risk factors for intelligent ships under different classification standards is constructed to lay a foundation for a further study of intelligent ship safe navigation, and at the same time avoid some risk factors in advance for the maritime management department, ship management companies, and ship design and research institutes.

Herein, novel microcapsules were designed and synthesized by emulsion polymerization and used for self-healing coating for magnesium alloy. Polyaniline (PANI) was used directly as a capsule shell, and thermoplastic acrylic resin was used as the core material. Polymerization processes of microcapsules were observed by optical microscopy, and some key polymerization parameters were discussed. Composite microcapsules were analyzed by scanning electron microscopy, infrared spectroscopy, and thermogravimetric analysis. The corrosion protection performance of microcapsule and epoxy varnish coatings with defect was tested by electrochemical impedance spectroscopy. Results showed that the microcapsule coating had a higher corrosion protection than epoxy varnish coating because capsule core acrylic resin could significantly improve the shield performance of the defect coating and capsule shell PANI could inhibit the corrosion reaction of magnesium alloy.

Livestock grazing has a significant impact on the biodiversity of nature grassland ecosystems, which is mainly regulated by climate factors. Soil microbes are essential components of biogeochemical cycles. However, the coupling effects of grazing with MAT (mean annual temperature) and MAP (mean annual precipitation) on soil microbial communities remain inconsistent. Our study considered the various climates in four grasslands as natural temperature and precipitation gradients combined with grazing intensity (GI). We collected and analyzed vegetation and soil physiochemical properties from four grasslands. Our results showed that climate factors (CF) changed β diversity of soil bacteria and fungi while grazing intensity and their interaction merely affected fungi β diversity. Furthermore, climate factors and grazing intensity impacted changes in vegetation and soil physiochemical properties, with their interaction leading to changes in EC and MBC. Our analysis revealed that climate factors contributed 13.1% to bacteria community variation while grazing intensity contributed 3.01% to fungi community variation. Piecewise SEM analysis demonstrated that MAT and MAP were essential predictors of bacteria β diversity, which was significantly affected by vegetation and soil carbon and nitrogen. At the same time, MAP was an essential factor of fungi β diversity and was mainly affected by soil nitrogen. Our study indicated that bacteria and fungi β diversity was affected by different environmental processes and can adapt to specific grazing intensities over time.

Previous research has primarily focused on static factors influencing cooperative behavior in social dilemmas, with less attention given to dynamic factors within group social interactions, such as positive feedback received during interactions, i.e., praise. This study, through a between-subjects online experiment with a single-factor, two-level design (praise: public praise/no praise), investigates the impact of praise on cooperative behavior changes across two rounds of a three-player public goods problem. Results revealed the following: (1) A positive correlation between individuals’ contributions across two rounds and a negative correlation with the number of correct answers in rule comprehension questions were evident; for men, a correlation between rule comprehension and first-round contributions was observed. (2) Multilevel model results showed that praise, role, and rule comprehension significantly positively affected contribution changes across two rounds; gender did not significantly affect contribution changes. Specifically, under public-praise conditions, contribution changes were greater. Publicly praised individuals showed positive or negative behavior changes, while those not praised in the same group showed positive changes. Men contributed significantly more in the first round than women, with no gender difference found in contribution changes. Rule comprehension positively predicted contribution changes, indicating that more correct answers led to greater positive changes in contributions. These results not only support the inferential social learning perspective, suggesting that through praise, individuals can infer external world perceptions and self-evaluations, affecting both the praised (positively or negatively) and positively influencing non-praised individuals in the same group, but also provide a theoretical basis and intervention strategies for team and organizational management in groups.

Flowers of Paulownia spp. wither and fall on a large scale after blooming in spring and have potential allelopathic effects on surrounding plants, including crops and weeds. In this study, the phytotoxic effects of water extracts of Paulownia tomentosa flower litter (EPF) on wheat (Triticum aestivum L.), lettuce (Lactuca sativa L.), green bristlegrass (Setaria viridis L.) and purslane (Portulaca oleracea L.) were evaluated in the laboratory. The mode of action of the phytotoxicity of EPF on lettuce seedlings was studied and the secondary metabolites in EPF were analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS). The results show that EPF significantly inhibited the seed germination and seedling growth of four target plants in a concentration-dependent manner. In addition, EPF could induce the excessive accumulation of reactive oxygen species (ROS) flowing with oxidative damage of the lipid bilayer of the biofilm, resulting in reduced cell viability and even apoptosis in lettuce. There were 66 secondary metabolites identified by LC-HRMS in P. tomentosa flowers. Among them, 10 compounds, including salicylic acid, caffeic acid, parthenolide, 7-hydroxycoumarin and abscisic acid (ABA), were all known allelochemicals. In summary, P. tomentosa flower litter displayed significant allelopathic effects, which were related to the accumulation of ROS in target plants. Phenolic acids, flavonoids as well as ABA are probably the main allelochemicals of P. tomentosa flowers.

Vaccinium dunalianum leaf buds make one of the most commonly used herbal teas of the Yi people in China, which is used to treat articular rheumatism, relax tendons, and stimulates blood circulation in the body. In addition, 6′-O-caffeoylarbutin (CA) is a standardized extract of V. dunalianum, which has been found in dried leaf buds, reaching levels of up to 31.76%. Because of the uncommon phenomenon, it is suggested that CA may have a potential therapeutic role in hyperlipidemia and thrombosis. This study was designed to study the efficacy of CA on treating hyperlipidemia and thrombosis and the possible mechanisms behind these effects. Hyperlipidemia and thrombosis zebrafish models were treated with CA to observe variations of the integrated optical density within the vessels and the intensity of erythrocyte staining within the hearts. The possible mechanisms were explored using network pharmacology and molecular docking. The results demonstrate that CA exhibits an excellent hypolipidemic effect on zebrafish at concentrations ranging from 3.0 to 30.0 μg/mL and shows thrombosis inhibitory activity in zebrafish at a concentration of 30.0 μg/mL, with an inhibition rate of 44%. Moreover, network pharmacological research shows that MMP9, RELA, MMP2, PRKCA, HSP90AA1, and APP are major targets of CA for therapy of hyperlipidemia and thrombosis, and may relate to pathways in cancer, chemical carcinogenesis-receptor activation, estrogen signaling pathway, and the AGE–RAGE signaling pathway in diabetic complications.

ObjectiveIn response to international fuel oil price fluctuations and the need to reduce greenhouse gas emissions, a meteorological shipping route decision-making system based on an BP neural network is proposed for ship managers to improve their ship operation efficiency while considering economic and environmental factors. MethodFirst, seven kinds of operational data, namely ship speed, revolutions per minute (RPM), mean draft, trim, cargo quantity, and influence of wind and waves, are extracted from the log-book and noon report, and the ship's fuel oil consumption is predicted by the BP neural network. A meteorological shipping route decision-making system based on the improved Dijkstra algorithm is then used to obtain the optimal route. ResultThrough the experimental analysis of a 12 335 gross ton multi-purpose vessel on the Yingkou-Incheon route, the goodness of fit between the predicted fuel consumption by BP neural network method and the measured value is 79.97%, the prediction effect is good; and meteorological shipping routes of 15 and 17 kn are obtained by the decision-making system. ConclusionThe meteorological shipping routes obtained by the decision-making system based on an BP neural network are more accurate and reliable. The results of this study can provide technical support for ship owners and maritime management departments in reducing fuel oil consumption and CO2 emissions.

In this work, we report ultra-sensitive detection of geometric fluctuations of semiconductor nanostructures using momentum-filtered spectroscopy. Our strategy is developed based on angle-resolved photoluminescence/absorption spectroscopic imaging technique. By filtering out signals with non-zero in-plane momentum using a confocal pinhole, ultra-sensitive detection of tiny geometric fluctuations with nanometer precision was made possible. In this way, we could optically detect geometric fluctuations of semiconductor nanostructures in real-time with a spatial resolution as high as ∼0.2 nm. Moreover, this technique is widely applicable to nanostructures where optical resonance can be formed.

Abstract Aim This study aimed to investigate the current situation of sarcopenia and anorexia of elderly maintenance haemodialysis patients and analyse the influencing factors. Design A cross‐sectional design was used in this study. Methods One hundred and twelve elderly patients on MHD in 3 haemodialysis centres in Sichuan, China, were selected. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia (AWGS). Anorexia was assessed with the Functional Assessment of Anorexia Cachexia Therapy/Anorexia Cachexia Subscale (FAACT/ACS). The relationship between sarcopenia and anorexia was analysed by logistic regression. Results The prevalences of sarcopenia and severe sarcopenia in elderly MHD patients were 52.7% and 39.3%, respectively, and the prevalence of anorexia was 25.9%. Severe sarcopenia was independently associated with anorexia, and weekly exercise frequency was independently associated with anorexia. The low SMI value and slow gait speed were strongly associated with anorexia. This study complied with the STROBE checklist.

IntroductionPositive personality traits have been associated with personal well-being in previous research. However, the pathways through which positive personality may affect social well-being remain unclear. The present study hypothesized that the cognitive strategies for achieving well-being (i.e., orientation to happiness) mediate the association between good personality and social well-being in the Chinese culture.MethodsA survey including the Good Personality Questionnaire, Social Well-being Scales, and Orientations to Happiness was administered to 1,503 Chinese secondary school students and adults.ResultsThe results indicated that orientation to meaning mediated the relation between good personality and social well-being, but not orientation to pleasure.DiscussionThis is in line with the normative well-being model and the cognition instrumental model of well-being, which contributes to developing more targeted interventions to promote social well-being in the Chinese cultural.

The primary goal of modern wheat breeding is to develop new high-yielding and widely adaptable varieties. We analyzed four yield-related agronomic traits in 502 wheat accessions under normal conditions (NC) and drought treatment (DT) conditions over three years. The genome-wide association analysis identified 51 yield-related and nine drought-resistance-related QTL, including 13 for the thousand-grain weight (TGW), 30 for grain length (GL), three for grain width (GW), five for spike length (SL) and nine for stress tolerance index (STI) QTL in wheat. These QTL, containing 72 single nucleotide polymorphisms (SNPs), explained 2.23 – 7.35% of the phenotypic variation across multiple environments. Eight stable SNPs on chromosomes 2A, 2D, 3B, 4A, 5B, 5D, and 7D were associated with phenotypic stability under NC and DT conditions. Two of these stable SNPs had association with TGW and STI. Several novel QTL for TGW, GL and SL were identified on different chromosomes. Three linked SNPs were transformed into kompetitive allele-specific PCR (KASP) markers. These results will facilitate the discovery of promising SNPs for yield-related traits and/or drought stress tolerance and will accelerate the development of new wheat varieties with desirable alleles.

ObjectiveTo investigate the effect of social support on stress, and to clarify the effect and mechanism of Online Emotional Support Accompany Group (OESAG).MethodsThe group members who signed up for the public welfare project “Psychological Rehabilitation Group Psychological Service under the COVID-19 Pandemic” were divided into the treatment group, the control group, and the blank group with 37 members each. The treatment group received OESAG intervention, the control group received online time management group intervention, and the blank group was the waiting group. The three groups of subjects were synchronously tested before and after the intervention group.ResultsAfter the OESAG intervention, compared with the control group and the blank group, the treatment group showed that perceived social support was improved, and loneliness and stress were decreased.ConclusionImproving social support can effectively reduce stress. OESAG can effectively improve social support and so too decrease stress. This study could help in designing effective psychological intervention measures to reduce the degree of stress symptoms and enhance both personal and social levels of coping with stressful events.

Bread wheat (Triticum aestivum L.) is one of the most extensively cultivated cereal crops around the world. Here, we investigated the population structure and genetic diversity of a panel mainly originated from two wheat agro-ecological regions (northern winter wheat region, NW; and the Huang-Huai River Valley’s facultative wheat region, HH) in China based on a 15K SNP array. Population genetic analysis revealed that the optimal population number (K) was three, and the three groups were roughly related to ecological regions, including NW (mainly Hebei), HH1 (Henan-Shaanxi), and HH2 (Shandong). Within HH, HH1 had a higher nucleotide diversity (π = 0.31167), minor allele frequency (MAF = 0.2663), polymorphism information content (PIC = 0.2668), and expected heterozygosity (Hexp = 0.3346) than HH2. Furthermore, our results demonstrated that genetic diversity decreases with the advancement of wheat breeding. Finally, inference of ancestry informative markers indicated that the genomes of the three pure groups from the three provinces (Hebei, Henan, and Shandong) of the two regions have genomic regions with different mosaic patterns derived from the two landrace groups. These findings may facilitate the development of wheat breeding strategies to target novel desired alleles in the future.

Abstract Background Larotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This open-label, phase 1b study is aimed to evaluate the efficacy, safety of larotinib in patients with advanced esophageal squamous cell carcinoma (ESCC) with EGFR overexpression or amplification pretreated with one or more system regimens, and to recommend an appropriate dose for its further study. Methods Patients received larotinib orally at 3 doses (250, 300, 350 mg), once daily. Clinical response was evaluated every 8 weeks according to RECIST v1.1 criteria by both investigators and independent radiology review (IRC). Results 81 patients were enrolled. The investigator-assessed overall response rate (ORR) was 13.7% (10/73), all responses were observed in the 350 mg group of which ORR up to 20.0% (10/50), with 10 of them having EGFR overexpression and 4 having EGFR amplification. Per IRC assessment, ORR for all patients and 350 mg group were 13.9% (10/72) and 16.3% (8/50). In the 350 mg group, median overall survival (OS) and progression-free survival (PFS) were 8.0 (95% CI 4.9–10.2) months and 3.4 (95% CI 2.4–3.7) months, respectively. The most common treatment-related adverse events (TRAEs) were diarrhea, rash, and palmar-plantar erythrodysesthesia syndrome, elevated AST/ALT, vomiting, similarly with other EGFR TKIs. Conclusions Larotinib demonstrated promising antitumor activity and manageable safety profiles in patients with pre-treated advanced ESCC with EGFR overexpression or amplification, especially at the dose of 350 mg, which showed better efficacy and acceptable safety. A phase 3 study is underway on 350 mg larotinib in ESCC patients with EGFR overexpression. Trial registration This trial was retrospectively registered on 25/03/2019, NCT03888092. https://clinicaltrials.gov/ct2/show/NCT03888092 .

Camellia fascicularis is a unique plant rich in bioactive components. However, the isolation of the active substances in C. fascicularis leaves via sequential extraction with solvents of different polarity and the determination of their antioxidant and antitumor activities have not been reported. In this study, the total methanol extract of C. fascicularis leaves was sequentially extracted with different polar solvents, and the corresponding petroleum ether extract (PEE), ethyl acetate extract (EAE), and water extract (WE) were analyzed for their contents in active substances such as flavonoids, polyphenols, polysaccharides, and saponins. The antioxidant ability of the polar extracts was investigated by determining their reducing power and the radical scavenging rate on 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl radicals, and CCK-8 and Annexin-FITC/propidium iodide staining assays were conducted to investigate their inhibitory effects on HCCLM6 and HGC27 tumor cells. The results showed that PEE had a high saponin content of 197.35 ± 16.21 mg OAE/g, while EAE and WE exhibited a relatively higher polysaccharide content of 254.37 ± 1.99 and 373.27 ± 8.67 mg GE/g, respectively. The EAE demonstrated the greatest reducing power and the strongest clearing abilities on ABTS and DPPH radicals with respective EC50 values of 343.45 ± 20.12 and 14.07 ± 0.06 μg/ml. Moreover, the antitumor ability of the different polar extracts was dose-dependent, with WE showing the most potent inhibitory ability against HCCLM6 and HGC27 cells.

IntroductionAlzheimer’s disease (AD) is the most common form of dementia worldwide. The biological mechanisms underlying the pathogenesis of AD aren’t completely clear. Studies have shown that the gut microbiota could be associated with AD pathogenesis; however, the pathways involved still need to be investigated.AimsTo explore the possible pathways of the involvement of gut microbiota in AD pathogenesis through metabolites and to identify new AD biomarkers.MethodsSeven-month-old APP/PS1 mice were used as AD models. The Morris water maze test was used to examine learning and memory ability. 16S rRNA gene sequencing and widely targeted metabolomics were used to identify the gut microbiota composition and fecal metabolic profile, respectively, followed by a combined analysis of microbiomics and metabolomics.ResultsImpaired learning abilities were observed in APP/PS1 mice. Statistically significant changes in the gut microbiota were detected, including a reduction in β-diversity, a higher ratio of Firmicutes/Bacteroidota, and multiple differential bacteria. Statistically significant changes in fecal metabolism were also detected, with 40 differential fecal metabolites and perturbations in the pyrimidine metabolism. Approximately 40% of the differential fecal metabolites were markedly associated with the gut microbiota, and the top two bacteria associated with the most differential metabolites were Bacillus firmus and Rikenella. Deoxycytidine, which causes changes in the pyrimidine metabolic pathway, was significantly correlated with Clostridium sp. Culture-27.ConclusionsGut microbiota may be involved in the pathological processes associated with cognitive impairment in AD by dysregulating pyrimidine metabolism. B. firmus, Rikenella, Clostridium sp. Culture-27, and deoxyuridine may be important biological markers for AD. Our findings provide new insights into the host-microbe crosstalk in AD pathology and contribute to the discovery of diagnostic markers and therapeutic targets for AD.

BackgroundTotally implantable venous access port (TIVAP) implantation is usually performed under general anesthesia with endotracheal intubation in children. Procedural sedation without endotracheal intubation has been applied to minor pediatric surgeries like central venous catheter insertion. To explore a more efficient and less invasive anesthesia mode to implant TIVAPs for children, we aimed to evaluate the efficacy and safety of procedural sedation using propofol and S(+)-ketamine compared with general anesthesia.MethodsSixty-six patients aged 6 months to 10 years undergoing TIVAP implantation were randomly allocated to two groups. Patients under procedural sedation [S(+)-ketamine-propofol (sketofol) group] were given target-controlled infusion of propofol 4 μg/ml using the Paedfusor model and S(+)-ketamine 0.5 mg/kg as induction, and had target-controlled infusion of propofol 3–4 μg/ml as maintenance. Patients in sketofol group received medium-flow oxygen inhalation through facemasks during surgery. Patients under general anesthesia (control group) were given propofol 2 mg/kg, cisatracurium 0.2 mg/kg, fentanyl 3 μg/kg as induction, and sevoflurane 0.8 minimum alveolar concentration as maintenance after endotracheal intubation. Primary outcome was the postoperative emergence agitation evaluated 5 min after awakening.ResultsPostoperative emergence agitation evaluated 5 min after awakening was lower in sketofol group versus control group [1.0 (0.5, 1.0) vs. 3.0 (2.0, 4.0); median difference (95% CI): 2.0 (1.0, 2.0); P < 0.001]. Time to awakening was significantly lower in sketofol group versus control group [15.0 (5.0, 23.0) vs. 26.0 (20.5, 37.5); median difference (95% CI): 11.0 (7.0, 19.0); P < 0.001], as well as time to discharge from post anesthesia care unit [35.0 (24.0, 45.0) vs. 45.0 (37.5, 59.5); median difference (95% CI): 10.0 (10.0, 23.0); P < 0.001]. Postoperative complications or adverse events were not reported in sketofol group.ConclusionsCompared to general anesthesia with endotracheal intubation, procedural sedation using propofol and S(+)-ketamine improves the postoperative emergence agitation right after the recovery of consciousness, and has advantage in shortening anesthetic recovery time for pediatric patients undergoing TIVAP implantation.

Cytokinin is an important endogenous hormone in plants performing a wide spectrum of biological roles. The type-A response regulators (RRAs) are primary cytokinin response genes, which are important components of the cytokinin signaling pathway and are involved in the regulation of plant growth and development. By analysis of the whole genome sequence of wheat, we identified 20 genes encoding RRAs which were clustered into eight homologous groups. The gene structure, conserved motifs, chromosomal location, and cis-acting regulatory elements of the TaRRAs were analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the expression levels of most of the TaRRAs increased rapidly on exogenous cytokinin application. Moreover, the TaRRA family members displayed different expression profiles under the stress treatments of drought, salt, cold, and heat. This study provides valuable insights into the RRA gene family in wheat and promotes the potential application of these genes in wheat genetic improvement.

Merchant ships sometimes fail to detect small ships at night and in poor visibility, leading to urgent situations and even collisions. Infrared (IR) cameras have inherent advantages in small target detection and become essential environmental awareness equipment on unmanned ships. The existing target detection models are complex and difficult to deploy on small devices. Lightweight detection algorithms are needed with the increase in the number of shipborne cameras. Therefore, herein, a lightweight model for small IR ship detection was selected as the research object. IR videos were collected in the Bohai Strait, the image sampling interval was calculated, and an IR dataset of small ships was constructed. Based on the analysis of the characteristics of the IR ship images, gamma transform was used to preprocess the images, which increased the gray difference between the target and background. The backbone of YOLOv5 was replaced with that of Mobilev3 to improve the computing efficiency. Finally, the results showed that the parameters of the proposed model were reduced by 83% compared with those of the YOLOv5m model, while the detection performance was almost the same.

Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. circARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p. In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.

ObjectivesShip collision is one of the main factors threatening the navigation safety of intelligent ships. A calculation model of ship collision risk should identify potential collision risks in time and provide the basic information for the intelligent ship's autonomous collision avoidance decision-making.MethodsThis paper first analyzes the domain-based collision risk parameter calculation model according to the degree of domain violation and other parameters. The navigation scene is divided into a single-ship encounter situation and an encounter between a ship and target ship group, and a new collision risk parameter calculation model for multi-ship encounters is given. Second, based on the Wiener process, the uncertainty of ship position prediction is modeled and obtained according to the Chi-squared distribution. Finally, a calculation method for collision risk parameters which considers the uncertainty of ship position prediction is given.ResultsOn this basis, the influence of ship position prediction uncertainty on ship collision risk is considered. ConclusionsThis method can further guarantee the safety of intelligent ships at sea.

Abstract Starch is the main component of wheat (Triticum aestivum L.) grain and a key factor in determining wheat processing quality. The Wx gene is the gene responsible for amylose synthesis. An ethyl methanesulfonate (EMS) mutagenized population was generated using common wheat cv. Gao 8901, a popular and high-quality cultivar in China. A waxy mutant (Wx-null) was isolated by screening M3 seeds with KI-I2 staining of endosperm starch. No obvious waxy proteins in Wx-null line were detected using Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). DNA sequencing revealed three SNPs and a 3-bp InDel in the first exon, and a 16-bp InDel at the junction region of the first Wx-A1 intron from the Wx-null line. Six SNPs were identified in Wx-B1 gene of Wx-null line compared to the wild-type Gao 8901, including four missense mutations. One nonsense mutation was found at position 857 in the fourth exon, which resulted in a premature stop codon. Expression levels of Wx genes were dramatically reduced in the Wx-null line. There were no detectable differences in granule size and morphology between Wx-null and wild-type, but the Wx-null line contained more B-type starch granules. The amylose content of the Wx-null line (0.22%) was remarkably lower compared to the wild-type Gao 8901 (24.71%). Total starch is also lower in the Wx-null line. The Wx-null line may provide a potential waxy material with high agronomic performance in wheat breeding programs.