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Abstract Background Different anesthetic drugs and techniques may affect survival outcomes for gastric cancer (GC) after surgery. In this study, we investigated the association between sedated and unsedated gastroscopy on survival outcomes in patients with GC after surgery. Methods This was a retrospective study of patients who were diagnosed with GC by gastroscopy and underwent gastrectomy from January 2013 to December 2017. They were grouped based on the examination modality: propofol-based sedated gastroscopy or unsedated gastroscopy. Propensity score matching (PSM) was used to balance the baseline variables. Survival outcomes and distant metastases were compared between these two groups. Results Finally, 673 patients were enrolled, 160 in the sedated gastroscopy group and 513 in the unsedated gastroscopy group. After PSM, there were 160 patients in each group. There was no significant difference in overall survival outcomes in the sedated gastroscopy group compared to the unsedated gastroscopy group before PSM (HR = 0.761, 95% CI: 0.531–1.091, P = 0.139) or after PSM (HR = 0.874, 95% CI: 0.564–1.355, P = 0.547). There was no significant difference in the incidence of distant metastases between the two groups before PSM (16.9% vs. 20.7%, P = 0.294) or after PSM (16.9% vs. 23.8%, P = 0.126). To confirm that our patients behaved similarly to other studies, we performed a multivariate analysis and the results showed that sex, pathological TNM stage, Borrmann type, adjuvant treatment, and surgical resection range were all independent factors affecting survival outcomes in our patients. Conclusion Our results showed no significant difference in the effects of sedated gastroscopy vs. unsedated gastroscopy on survival outcomes or distant metastases of patients after gastrectomy for GC.

Affective disorders, such as depression, are commonly associated with the development of chronic pain, but the underlying mechanisms still remain unclear. The dopaminergic system, located in the midbrain, is considered one of the regions where algesia and emotional processing overlap. This suggests a structural basis hypothesis for the comorbidity of chronic pain and depression, highlighting the interplay between nociceptive and affective processing. But there are more and more evidences show that somatic and head/facial pain involve different neuronal overlap. In previous study, the research show that VTA dopaminergic system involved in pIONT surgery induced depressive-like behaviors in mice. But there still no evidence shows if chronic somatic pain will induce depressive-like behaviors and which neuronal circle pathway is underly. In this study, we assessed depressive-like behaviors and performed artificial interference of VTA (ventral tegmental area) dopaminergic neurons in a mouse model of chronic peripheral neuropathic pain induced by the spared nerve injury (SNI) model. After a 4-week duration of hyperalgesia and allodynia resulting from SNI surgery, social withdraw and other depressive-like behaviors were observed in the SNI group. Furthermore, the dopaminergic cells’ excitability in VTA were significantly increased in SNI mice. The excitability alteration was improved play a key role in the development and modulation of the chronic peripheral neuropathic pain-induced depressive-like behaviors. It has been shown pain and affections have structural and functional circuits to interact with each other, therefore the neuroplastic changes and functional role of VTA dopaminergic neurons within these circuits may serve as potential targets for understanding and therapeutically addressing the development of depressive-like symptoms accompanied by prolonged pain syndromes in humans.

Abstract Aims Both hypercapnia and hypocapnia are common in patients with acute heart failure (AHF), but the association between partial pressure of arterial carbon dioxide (PaCO2) and AHF prognosis remains unclear. The objective of this study was to investigate the connection between PaCO2 within 24 h after admission to the intensive care unit (ICU) and mortality during hospitalization and at 1 year in AHF patients. Methods and results AHF patients were enrolled from the Medical Information Mart for Intensive Care IV database. The patients were divided into three groups by PaCO2 values of 45 mmHg. The primary outcome was to investigate the connection between PaCO2 and in‐hospital mortality and 1 year mortality in AHF patients. The secondary outcome was to assess the prediction value of PaCO2 in predicting in‐hospital mortality and 1 year mortality in AHF patients. A total of 2374 patients were included in this study, including 457 patients in the PaCO2 45 mmHg group. The in‐hospital mortality was 19.5%, and the 1 year mortality was 23.9% in the PaCO2 45 mmHg group was associated with an increased risk of in‐hospital mortality (HR 1.387, 95% CI 1.050–1.832, P = 0.021); the 1 year mortality showed no significant difference (HR 1.286, 95% CI 0.995–1.662, P = 0.055) compared with the PaCO2 = 35–45 mmHg group. The Kaplan–Meier survival curves showed that the PaCO2

Abstract Climate change is one of the biggest challenges to the world at present. Tomato is also suffered from devastating yield loss due to climate change. The domesticated tomato (Solanum lycopersicum) is presumed to be originated from the wild tomato (S. pimpinellifolium). In this study, we compared the climate data of S. pimpinellifollium with the domesticated tomato, predicted the suitable regions of S. pimpinellifollium in China using MaxEnt model and assessed their tolerance to drought stress. We found that the predicted suitable regions of wild tomato are highly consistent with the current cultivated regions of domesticated tomato, suggesting that the habitat demand of domesticated tomato descended largely from its ancestor, hence the habitat information of wild tomato could provide a reference for tomato cultivation. We further predicted suitable regions of wild tomato in the future in China. Finally, we found that while average drought tolerance between wild and domesticated tomato accessions shows no difference, tolerance levels among wild tomato accessions exhibit higher variation, which could be used for future breeding to improve drought resistance. To summarize, our study shows that suitable regions of wild tomato provide insights into domesticated tomato cultivation in China.

The annual prevalence of gastric cancer has increased in recent years. Curcumin (CUR) has shown great potential in the treatment of gastric cancer; however, its low bioavailability and poor efficacy hinder its widespread clinical application. Additionally, CUR has been found to be excellent photosensitizer in photodynamic therapy. In this study, the Fe-based metal-organic framework (MOF) Fe Tetrakis (4-carboxyphenyl) porphyrin (Fe-TCPP，FT) was used as a photosensitizer and mononuclear agent. The natural anti-tumor active ingredient CUR was loaded as both a chemotherapeutic agent and photosensitizer to form the nanoparticles CUR@FT (CF). Finally, a cell-penetrating peptide (CPP10) was modified on the surface of the nanoparticles to construct a drug delivery system (named CPP10-PEG@CUR@FT, CCF) that could actively target tumor cells while exerting a synergistic therapeutic effect of chemotherapy and photodynamic therapy. This can improve the efficacy of CUR as a chemotherapeutic drug or photosensitizer, and the high drug load and pH sensitivity of FT nanoparticles provide an excellent carrier for the efficient delivery of CUR. The polyethene glycol (PEG)-conjugated CPP10 (PEG-CPP10) coating allows nanoparticles to specifically target gastric cancer cells, significantly improving the absorption of nanoparticles in vivo and in vitro and improving biosafety. We evaluated the thermal stability, drug loading capacity, and safety of FT as a drug delivery vehicle. We also assessed the in vitro photodynamic performance and toxicity of various nanoparticles and the targeting and biocompatibility of CPP10-PEG@CUR@FT. CPP10-PEG@CUR@FT could specifically target tumor cells, and its effect on killing gastric cancer cells (MKN45) under light was much stronger than that of free CUR. Its toxicity and side effects to other organs and tissues are low, offering good biosafety. The experimental results showed that FT and CUR exerted synergistic effects on photodynamic therapy and chemotherapy. In summary, our novel CUR-loaded targeted nano drug delivery system offers significant advantages by combining photodynamic therapy and chemotherapy for tumor treatment. This approach introduces a new concept for integrating chemotherapy, photodynamic therapy and targeted drug delivery, potentially providing a new strategy for the clinical treatment of gastric cancer.

Due to the non-specific distribution of drugs in the body and the low concentration at the tumor site in traditional chemotherapy, there are challenges associated with significant side effects and tumor resistance. Therefore, a drug delivery system (DDS) urgently needs to be developed that can precisely target tumors. Metal-organic frameworks (MOFs) possess advantageous characteristics derived from organic and inorganic materials, including small particle size, large specific surface area, high drug loading capacity, adjustable structure and pore size, as well as ease of modification. Consequently, MOFs offer unique advantages for designing active targeting, passive targeting, and stimulus-responsive targeting strategies and have become a hot topic of current research on tumor-targeted drug delivery systems. This review will elaborate on the application of MOFs in tumor-targeted drug delivery systems from the perspective of different targeting strategies. We hope that this paper can provide assistance for tumor-targeted therapy.

AimTo compare the effects of midazolam, propofol, and dexmedetomidine monotherapy and combination therapy on the prognosis of intensive care unit (ICU) patients receiving continuous mechanical ventilation (MV).Methods11,491 participants from the Medical Information Mart for Intensive Care (MIMIC)-IV database 2008–2019 was included in this retrospective cohort study. The primary outcome was defined as incidence of ventilator-associated pneumonia (VAP), in-hospital mortality, and duration of MV. Univariate and multivariate logistic regression analyses were utilized to evaluate the association between sedation and the incidence of VAP. Univariate and multivariate Cox analyses were performed to investigate the correlation between sedative therapy and in-hospital mortality. Additionally, univariate and multivariate linear analyses were conducted to explore the relationship between sedation and duration of MV.ResultsCompared to patients not receiving these medications, propofol alone, dexmedetomidine alone, combination of midazolam and dexmedetomidine, combination of propofol and dexmedetomidine, combination of midazolam, propofol and dexmedetomidine were all association with an increased risk of VAP; dexmedetomidine alone, combination of midazolam and dexmedetomidine, combination of propofol and dexmedetomidine, combination of midazolam, propofol and dexmedetomidine may be protective factor for in-hospital mortality, while propofol alone was risk factor. There was a positive correlation between all types of tranquilizers and the duration of MV. Taking dexmedetomidine alone as the reference, all other drug groups were found to be associated with an increased risk of in-hospital mortality. The administration of propofol alone, in combination with midazolam and dexmedetomidine, in combination with propofol and dexmedetomidine, in combination with midazolam, propofol and dexmedetomidine were associated with an increased risk of VAP compared to the use of dexmedetomidine alone.ConclusionDexmedetomidine alone may present as a favorable prognostic option for ICU patients with mechanical ventilation MV.

Objective Total caving coal mining in the upper reaches of the Yellow River in Inner Mongolia has resulted in large areas of subsidence, causing frequent ecological and environmental problems on the surface. Methods For the study of the surface crack development rule of the goaf and collapse stress and the displacement field evolution characteristics, for a string of the Chuancaogedan Coal Mine 6102 working face as the research object. The distribution range and rule of surface cracks were found by UAV aerial survey, a FLAC3D numerical model was constructed to analyze the variation of stress and displacement of surrounding rock in goaf. Results The results of the analysis were combined with the results of UAV mutual authentication. The results show that (1) The collapse is mainly in the form of ground fissures, which are mainly distributed in the northwest and midwest of the mine. There are two types of ground fractures in the working face. One type of arc-shaped stepped fracture group is distributed in parallel and appears at intervals of 5-20 m. Most of them form staggered platforms with a step height of 15-130 cm, and the fractures develop in the direction of the vertical working face advance at a deviation angle of 3°-5°. For the other kind of linear edge crack belts, exhibiting severe tensile damage, were observed along the working face peripheral, belt development can occur, a few can be spread in the inside of the working face, and the distance from the outermost crack to the working face is 38.53 m. (2) During the excavation of the underground coal seam, an obvious saddle-shaped tensile stress concentration area appears in the roof of the goaf, and with the advance of excavation, the tensile stress in the surface concentration area first increases and then decreases, with a maximum value of 0.181 MPa. (3) Complete collapse occurred at the top of the goaf, with the maximum surface vertical displacement of approximately 5.5 m located at the middle of the goaf. The maximum surface horizontal displacement was located above the coal pillar of the goaf, with a maximum value of 1.93 m. (4) Numerical simulation results regarding settlement and crack angles were found to align closely with the UAV survey data. Conclusion The research results can provide a reference for the solution of ecological environmental problems caused by coal seam mining.

BackgroundBleomycin is a glycopeptide antibiotic with outstanding anti-tumor effects. A major adverse effect of bleomycin is lung fibrosis. However, the development of cataracts as a severe adverse effect has not been reported.Case summaryHerein, we describe the first case of cataract induced by bleomycin therapy in a 22-year-old male with testicular cancer. After surgical intervention and following five successive chemotherapy cycles of the BEP regimen, including bleomycin, etoposide and cisplatin, the patient reported a gradual painless loss of vision, with substantial decline in visual ability, especially in the right eye. Following comprehensive eye examinations, a cataract was diagnosed. Eventually, the patient underwent phacoemulsification and received replacement of the intraocular lenses.ConclusionBleomycin can cause cataracts, which induces a significant loss of vision. Therefore, clinicians should observe early symptoms and properly adjust treatment to prevent aggravation of symptoms.

Abstract The converter transformer is an essential part of the DC transmission system. Compared with the traditional oil‐impregnated AC transformer, the main insulation of the converter transformer bears more complex electric field aging stress during long‐term operation. The influence of the proportion of AC components in the AC/DC composite electric field on insulation aging is still unclear. Therefore, a combined aging test platform of composite electric field and thermal was built in the laboratory, and accelerated aging tests of oil‐paper insulation under different AC/DC ratios were carried out. Through the time‐frequency domain dielectric response characteristics of oil‐paper insulation, the quantitative relationship between the time‐frequency domain dielectric response characteristic parameters and AC proportional coefficient in different aging stages was obtained. The results show that the influence of the AC component on the aging of the oil‐impregnated pressboard is more prominent. The maximum relaxation polarization time and the maximum exponential coefficient of polarization–depolarization current (PDC) can effectively characterize the aging of oil‐paper insulation. Meanwhile, to accurately assess the insulation state of the converter transformer, this paper established the equivalent dielectric relaxation model for the main insulation structure. A quantitative assessment method for moisture content and aging of oil‐paper insulation based on time‐frequency domain dielectric response was proposed. The influence of transformer oil conductivity, test temperature, and main insulation structure was eliminated. The effectiveness of this method was verified by comparative tests, the maximum error for DP is 20, and the maximum error for moisture content is 0.15%. The research results of this paper can provide theoretical support for on‐site assessment of converter transformer insulation status.

Abstract Solitary waves are unique in nonlinear systems, but their formation and propagation in the nonlinear fluid-structure interactions have yet to be further explored. As a typical nonlinear system, the buckling of solid thin films is fundamentally related to the film-substrate interface that is further vulnerable to environments, especially when fluids exist. In this work, we report an anomalous, solitary-wave-like blister (SWLB) mode of MoS2 thin films in a humid environment. Unlike the most common telephone-cord and web buckling deformation, the SWLB propagates forward like solitary waves that usually appear in fluids and exhibits three-dimensional expansions of the profiles during propagation. In situ mechanical, optical, and topology measurements verify the existence of an interfacial water nanolayer, which facilitates a delamination of films at the front side of the SWLB and a readhesion at the tail side owing to the water nanolayer-induced fluid-structure interaction. Furthermore, the expansion morphologies and process of the SWLB are predicted by our theoretical model based on the energy change of buckle propagation. Our work not only demonstrates the emerging SWLB mode in a solid material but also sheds light on the significance of interfacial water nanolayers to structural deformation and functional applications of thin films.

BackgroundA large number of studies have found that the musculoskeletal injury of modern and contemporary dancers has a high incidence. Previous publications have indicated that there are many potential factors that are related to dancing injury; however, they have not been proven, and even some data are conflicting in different research.ResultsThe search yielded 18 prospective studies reporting on professional and pre-professional modern or contemporary dancers from companies and schools. The prevalence of modern and contemporary dancers was 0.82 (95% CI: 0.74~0.90). The injury proportion of trauma, overuse, ankle and foot, lower extremity, joint and ligaments, muscle and tendons, and time-loss were 0.40, 0.26, 0.49, 0.34, 0.33, and 0.29 in the total number of injuries. There was no evidence of a significant difference in sex, age, and education program. The factors of BMI and injury history achieved statistical significance, and the p-values were less than 0.01.ConclusionBased on the results of this article, BMI and injury history may be risk factors for injury in contemporary and modern dancers. Modern and contemporary dancers have a high prevalence of musculoskeletal injuries. Lower extremity injuries are the most common in the whole body, with injuries to the foot and ankle being more frequent. The mechanism of injury is mostly overuse injury, and the injured tissues are mostly muscle tendons and joint ligaments.

Virtual power plants (VPPs), serving as an integration and coordination platform for energy sources, have been rapidly developed in recent years. With the rapid expansion of distributed energy sources, disturbance problems within the VPP and cluster are becoming increasingly prominent. In this study, we commence by addressing the internal fluctuations within the VPP through the construction of a source–load uncertainty model. Then, we integrate the Nash bargaining game theory, treating different VPPs as participants in the game. This approach significantly mitigates disturbances within both VPPs and the cluster through the negotiation of power trading strategies. In addition, the coordination between VPPs and their coordination with the distribution network in the network-wide interaction is considered, and an optimization algorithm for distributed electricity trading based on the alternating direction method of multipliers is proposed to solve the model. The results show that the proposed model effectively copes with the internal and external disturbances of the VPP, improves the system’s ability to cope with the uncertainty risk, and reduces the operation cost.

Ischnothyreus Simon, 1893 is one of the most speciose genera of Oonopidae, with 124 extant species mainly distributed in the Old World. Currently, 27 species are known in China.A new species, Ischnothyreus ruyuanensis Tong, sp. n., is described from Guangdong Province, China. Morphological description and illustrations are provided.

Abstract Dempster–Shafer evidence theory is an effective method to deal with information fusion. However, how to deal with the fusion paradoxes while using the Dempster’s combination rule is still an open issue. To address this issue, a new basic probability assignment (BPA) generation method based on the cosine similarity and the belief entropy was proposed in this paper. Firstly, Mahalanobis distance was used to measure the similarity between the test sample and BPA of each focal element in the frame of discernment. Then, cosine similarity and belief entropy were used respectively to measure the reliability and uncertainty of each BPA to make adjustments and generate a standard BPA. Finally, Dempster’s combination rule was used for the fusion of new BPAs. Numerical examples were used to prove the effectiveness of the proposed method in solving the classical fusion paradoxes. Besides, the accuracy rates of the classification experiments on datasets were also calculated to verify the rationality and efficiency of the proposed method.

The Sustainable Development Goals, adopted by all United Nations Member States, emphasize sustainable cities and communities, aiming to strengthen development planning and foster positive links between urban and rural areas by 2030. As the newly leading platform for urbanization development, characteristic towns (‘Tese Xiaozhen’ in Chinese) contribute to the target of sustainable urbanisation, wherein town policies are especially important for leading the sound development of characteristic towns. However, the effect of these characteristic towns policies remains uncertain. Additionally, most related studies have utilized qualitative methodologies in policy evaluation, which may be inadequate to guide actual practice. Thus, in order to accurately acknowledge the effect of characteristic towns policies, a policy evaluation framework is established in this paper, utilising the multiple streams theory, text mining and the Policy Modelling Consistency Index model (PMC-Index model). Then, taking 225 policy documents promulgated in China from 2015 to 2022 as the research objects, policy evaluation indicators were selected by combining the multiple streams theory to improve the PMC-Index model and a text mining method. Thereafter, an empirical analysis was conducted to evaluate the consistency of 10 characteristic towns policies chosen. The results indicate that the mean value of the PMC indexes of the 10 examined policies is 7.13 in the total of 9 points, which means that the general performance of the characteristic town policies is satisfactory, yet the low scores in terms of effectiveness, content, and guarantee. In the end, some recommendations and suggestions are proposed for clarifying administrative attributes, optimizing the integration of urban and rural resources, and adjusting the policy hierarchy to a bottom-up approach. This study not only provides a policy evaluation framework to comprehensively understand the consistency of global urbanization policies but also offers a beneficial reference for promote urban–rural sustainable development.

Astragalus membranaceus (A. membranaceus) is a homologous plant with high medicinal and edible value. Therefore, the extraction methods of Astragalus polysaccharide (APS) have attracted the attention of many research groups, but the yield of the active components is still not high. The aim of this study was to extract APS by a semi-bionic extraction method, optimize the extraction process, and evaluate the anti-aging activities of APS in vivo. The results showed that the APS yield was 18.23% when extracted by the semi-bionic extraction method. Anti-aging evaluation in rats showed that APS extracted by this method significantly decreased the malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity to cope with D-galactose-induced aging. Serum metabolomic analysis indicated that a total of 48 potential biomarkers showed significant differences, mainly involving 5 metabolic pathways. These altered metabolic pathways were mainly related to energy metabolism, amino acid metabolism, and lipid metabolism. These results indicated that the semi-bionic extraction method can effectively improve the yield of APS, and the extracted APS exhibited anti-aging activity in rats. Our study provided a novel and effective method to extract APS and indicated that APS can be used as functional food and natural medicine to delay aging and prevent its complications.

Abstract Background Migraine is a neurological condition characterized by chronic inflammation. However, not much is known about the potential role of peripheral blood immune cells in the pathophysiology of migraine. Methods We investigated the status of peripheral blood immune cells of 15 adults with frequent episodic or chronic migraine recruited chronologically from a randomized clinical trial (RCT) on Nutrition for Migraine (NCCIH 5R01AT007813-05) and 15 non-migraine, healthy volunteers (control) matched by age, gender, and Body Mass Index (BMI). Continuous variables were presented as means ± standard deviationas well as medians, and comparisons between patients and healthy volunteers were performed with non-parametric Wilcoxon signed rank tests. Statistical analysis was performed using Stata (StataCorp. 2019. Stata Statistical Software). Fluorescence-Activated Cell Sorting (FACS) data were processed using FlowJo software (Ashland, OR: Becton, Dickenson and Company; 2019). Results We observed that migraineurs had a significantly lower percentage of non-classical monocytes (CD14+CD16++) in blood circulation, compared to the control group. In addition, Migraineurs also showed a significantly lower percentage of blood CD3+CD4+ helper T cells and CD4+CD25+ regulatory T cells, compared to controls. Differences in leukocyte surface markers between chronic migraine patients and their matched controls were more prominent than those between episodic migraine patients and their matched controls. Conclusions Our results suggest that migraine is associated with dysregulated peripheral immune homeostasis and that inflammation and autoimmunity may play a role in its pathophysiology.

The study of the mechanical properties of twisted van der Waals structures can provide important information about their interlayer coupling and electronic behaviour. Here, the authors report a nanoindentation-based technique to determine the interlayer shear stress in bilayer MoS2, showing its independence as a function of the twist angle.

Effective and economical processes for the advanced treatment of coking wastewater were urgently needed to reduce the persistent organic pollutants of external drainage. In the present work, we investigated the degradation of organic pollutants in coking wastewater through IHC/FO (imping stream hydrodynamic cavitation (IHC) coupled with the Fenton oxidation (FO) process) and IHC alone for their feasibility in the advanced treatment of coking wastewater. To select the optimum parameters, attention was paid to the effects of main operation conditions including inlet fluid pressure, medium temperature, initial pH, reaction time, and initial Fe(II) and initial H2O2 concentrations. The results showed that the effects of conditions that need energy to be maintained (such as initial pH and inlet pressure) on the organic pollutant removal efficiency through IHC/FO were less pronounced than those through IHC alone. Moreover, the application of IHC/FO could remove more organic pollutants from coking wastewater than IHC even at an energy-efficient condition. For example, the highest COD removal efficiency of 12.5% was achieved in the IHC treatment at 0.4 MPa, pH 3, and 60 min for the reaction time. In the case of IHC/FO, the maximum COD removal of 33.2% was obtained at pH 7, 0.1 MPa, 12 mmol/L H2O2, and 3 mmol/L Fe2+ after reacting for 15 min. The ultraviolet and visible spectrophotometry (UV-Vis) absorption spectra and gas chromatography and mass spectrometry (GC–MS) analysis further revealed that the kinds and amounts of pollutants (especially those that had benzenes) remaining in water treated through IHC/FO were much fewer and smaller than in water treated through IHC alone. The better performances of IHC/FO than IHC alone were likely related to the more hydroxyl radicals produced through IHC/FO. Taken together, our findings indicate that IHC/FO has great application potential in the advanced treatment of coking wastewater.

Abstract Background Limited by difficulties in early detection and availabilities of effective treatments, pancreatic cancer is a highly malignant disease with poor prognosis. Nuclear receptors are a family of ligand‐dependent transcription factors that are highly druggable therapeutic targets playing critical roles in human physiological and pathological development, including cancer. In this study, we explored the therapeutic potential as well as the molecular mechanisms of liver X receptor (LXR) agonist GW3965 in pancreatic cancer. Methods Soft‐agar colony formation assay, xenograft tumors, Oligonucleotide microarray, Reverse transcription real‐time polymerase chain reaction, Western immunoblotting and Immunohistochemistry were used in this study. Results We demonstrated pleotropic in vitro activities of GW3965 in pancreatic cell lines MIA PaCa‐2 and BXPC3 including reduction of cell viability, inhibition of cell proliferation, stimulation of cell death, and suppression of colony formation, which translated to significant inhibition of xenograft tumor growth in vitro. By mapping the gene expression profiles, we identified the up‐regulations of 188 and the down‐regulations of 92 genes common to both cell lines following GW3965 treatment. Genes responsive to GW3965 represent a variety of biological pathways vital for multiple cellular functions. Specifically, we identified that the activating transcription factor 4/thioredoxin‐interacting protein/regulated in development and DNA damage responses 1/mechanistic target of rapamycin (ATF4/TXNIP/REDD1/mTOR) signaling critically controls GW3965‐mediated regulation of cell proliferation/death. The significance of the ATF4/TXNIP/REDD1/mTOR pathway was further supported by associated expressions in xenograft tumors as well as human pancreatic cancer samples. Conclusions This study provides the pre‐clinical evidence that LXR agonist is a promising therapy for pancreatic cancer.

Hibiscus manihot L. seed oil is an emerging high-value edible vegetable oil that also has a variety of important health functions, and concerns about its pressing method have great significance for commercial and consumer health. This study compared triacylglycerols (TAGs), diacylglycerol (DAG), free fatty acids (FFAs), and volatile flavor compounds for discriminating cold-pressed oil from hot-pressed oil. The profiles of TAGs, DAGs, FFAs, and flavor compounds were established by a lipidomic approach and electronic-nose (E-nose). Our results demonstrated that a slight decrease in TAG content and a significant increase in FFA and DAG contents were observed after roasting. The E-nose results showed that sulfides, terpenes, methane, compounds containing oxygen and nitrogen, alcohol and aromatic compounds greatly influenced the oil flavor. The PCA result of the E-nose data indicated that flavor compounds showed great promise for distinguishing the two samples. The quality indices and the oxidative stability of oil samples were detected to identify their nutritional value and edible quality. This study revealed that roasting greatly influenced the lipid and flavor substances of the Hibiscus manihot L. seed oil. Our findings could provide useful information on the impact of the pressing method for Hibiscus manihot L. seed oil.

Fermented sausage is popular with many consumers because of its distinctive flavor, but the safety of it has attracted widespread attention. At present, nitrite is widely used in fermented meat products because of its ideal color and bacteriostatic effect, but nitrite can be transformed into nitrosamines, which cause strong carcinogenic effects. Therefore, it is urgent to actively explore safe and efficient nitrite substitutes. In this study, cranberry powder was selected as a natural substitute for nitrite during the production of fermented sausage due to its unique antioxidant and bacteriostatic properties. The results showed that adding an appropriate amount of cranberry powder (5 g/kg) promoted a better color of the fermented sausage and promoted the accumulation of aromatic compounds. Furthermore, Pediococcus and Staphylococcus became the dominant species, accounting for more than 90% in all samples. According to the Pearson correlation analysis, Staphylococcus and Pediococcus had positive effects on the quality characteristics of fermented sausage products. This study provided the latest information on the application of cranberry powder as a natural substitute for nitrite in the process of manufacturing fermented sausage, and it also introduced an advanced solution to improve the quality characteristics and safety of fermented sausage products during processing.

Abstract Toxoplasma gondii is a worldwide food-borne parasite that can infect almost all warm-blooded animals, including humans. To date, there are no effective drugs to prevent or eradicate T. gondii infection. Recent studies have shown that probiotics could influence the relationship between the microbiota and parasites in the host. Koumiss has been used to treat many diseases based on its probiotic diversity. Therefore, we explored the effect of koumiss on T. gondii infection via its effect on the host intestinal microbiota. BALB/c mice were infected with T. gondii and treated with PBS, koumiss and mares’ milk. Brain cysts were counted, and long-term changes in the microbiota and the effect of koumiss on gut microbiota were investigated with high-throughput sequencing technology. The results suggested that koumiss treatment significantly decreased the cyst counts in the brain (P

The development of vaccines that can efficiently prevent the infection of SARS-CoV-2 is necessary to fight the COVID-19 epidemic. mRNA vaccine has been proven to induce strong humoral and cellular immunity against SARS-CoV-2. Here, we studied the immunogenicity and protection efficacy of a novel mRNA vaccine SYS6006. High expression of mRNA molecules in 293T cells was detected. The initial and boost immunization with a 21-day interval was determined as an optimal strategy for SYS6006. Two rounds of immunization with SYS6006 were able to induce the neutralizing antibodies against the SARS-CoV-2 wild-type (WT) strain, and Delta and Omicron BA.2 variants in mice or non-human primates (NHPs). A3rd round of vaccination could further enhance the titers of neutralization against Delta and Omicron variants. In vitro ELISpot assay showed that SYS6006 could induce memory B cell and T cell immunities specifically against SARS-CoV-2 in mice. FACS analysis indicated that SYS6006 successfully induced SARS-CoV-2-specific activation of T follicular helper cell (Tfh) and Th1 cell, and did not induce CD4+Th2 response in NHPs. SYS6006 vaccine could significantly reduce the viral RNA loads and prevent lung lesions in Delta variant infected hACE2 transgenic mice. Therefore, SYS6006 could provide significant immune protection against SARS-CoV-2.

Toxoplasma gondii is an obligate intracellular parasite that infects nucleated cells of all warm-blooded animals, and most patients have latent infections. The latent infection will be reactivated in the immunocompromised or immunocompromised individuals, which will lead to severe toxoplasmosis. At present, less research has been focused on the reactivation of T. gondii infection. Koumiss is a kind of fermented milk made from fresh mare’s milk through natural fermentation that can be applied to clinical and rehabilitation medicine to mitigate the development of various diseases due to its unique functional characteristics. In this study, we explored the antagonistic effect of koumiss on reactivation of T. gondii infection. Mice were treated with dexamethasone to establish a reactivation model after infection with T. gondii and then treated with koumiss. The survival rate, SHIRPA test, serum cytokine levels, organ parasite burden and intestinal microbiota were measured, respectively. Our results showed that koumiss treatment improved the clinical symptoms of mice, significantly reduced the organ parasite burden of mice, and improved the composition and structure of intestinal flora. This study provides new evidence for the alleviation and treatment of toxoplasmosis and provides a novel idea for the development and utilization of koumiss.

Toxoplasma gondii is an important food-borne zoonotic parasite, and approximately one-third of people worldwide are positive for T. gondii antibodies. To date, there are no specific drugs or vaccines against T. gondii. Therefore, developing a new safe and effective method has become a new trend in treating toxoplasmosis. Koumiss is rich in probiotics and many components that can alleviate the clinical symptoms of many diseases via the functional characteristics of koumiss and its regulation of intestinal flora. To investigate the antagonistic effect of koumiss on T. gondii infection, the model of acute and chronic T. gondii infection was established in this study. The survival rate, SHIRPA score, serum cytokine levels, brain cyst counts, β-amyloid deposition and intestinal flora changes were measured after koumiss feeding. The results showed that the clinical symptoms of mice were improved at 6 dpi and that the SHIRPA score decreased after koumiss feeding (P < 0.05). At the same time, the levels of IL-4, IFN-γ and TNF-α decreased (P < 0.001, P < 0.001, P < 0.01). There was no significant difference of survival rate between koumiss treatment and the other groups. Surprisingly, the results of chronic infection models showed that koumiss could significantly reduce the number of brain cysts in mice (P < 0.05), improve β-amyloid deposition in the hippocampus (P < 0.01) and decrease the levels of IFN-γ and TNF-α (P < 0.01, P < 0.05). Moreover, koumiss could influence the gut microbiota function in resisting T. gondii infection. In conclusion, koumiss had a significant effect on chronic T. gondii infection in mice and could improve the relevant indicators of acute T. gondii infection in mice. The research provides new evidence for the development of safe and effective anti-T. gondii methods, as well as a theoretical basis and data support for the use of probiotics against T. gondii infection and broadened thoughts for the development and utilization of koumiss.

Nonintrusive load monitoring (NILM) plays a key role in the real-time electricity consumption monitoring of household appliances. However, it is difficult to realize high precision load identification by using a single waveform feature. Therefore, this article proposes a two-stream convolutional neural network based on current time-frequency feature fusion for nonintrusive load identification. First, a time series image coding method for current time-frequency multi-feature fusion is proposed. The method can extract the time domain and frequency domain features of the current timing signal effectively. Then, we present a two-stream neural network combining the gated recurrent unit (GRU) and a two-dimensional convolutional neural network (2D-CNN) to improve the load identification performance. Finally, the experimental results on the PLAID and IDOUC datasets show that the proposed model outperforms the state-of-the-art methods.

AimsAcute decompensated right heart failure (RHF) in chronic precapillary pulmonary hypertension is often typified by a swiftly progressive syndrome involving systemic congestion. This results from the impairment of the right ventricular filling and/or a reduction in the flow output of the right ventricle, which has been linked to a dismal prognosis of short duration. Despite this, there are limited therapeutic data regarding these acute incidents. This study examined the effect of levosimendan on acute decompensated RHF in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH).MethodsThis retrospective study included 87 patients with confirmed CTD-PAH complicated acute decompensated RHF between November 2015 and April 2021. We collected biological, clinical, and demographic data, as well as therapy data, from patients with acute decompensated RHF who required levosimendan treatment in the cardiac care unit (CCU) for CTD-PAH. The patients were divided into two groups according to the levosimendan treatment. Patient information between the two groups was systematically compared in hospital and at follow-up.ResultsOxygen saturation of mixed venose blood (SvO2), estimated glomerular filtration rate (eGFR), 24-h urine output, and tricuspid annular plane systolic excursion (TAPSE) were found to be considerably elevated in the levosimendan cohort compared with the control cohort. Patients in the levosimendan cohort exhibited considerably reduced levels of C-reactive protein (CRP), white blood cell (WBC), troponin I, creatinine, NT-proBNP, and RV diameter compared with those in the control cohort. A higher survival rate was observed in the levosimendan cohort.ConclusionsLevosimendan treatment could effectively improve acute decompensated RHF and systemic hemodynamics in CTD-PAH patients, with positive effects on survival in hospital and can, therefore, be considered as an alternative treatment option for improving clinical short-term outcomes.

PurposeSubtraction coronary CT angiography (CCTA) may reduce blooming and beam-hardening artifacts. This study aimed to assess its value in improving the diagnostic accuracy of readers with different experience levels.MethodWe prospectively enrolled patients with target segment who underwent CCTA and invasive coronary angiography (ICA). Target segment images were independently evaluated by three groups of radiologists with different experience levels with CCTA using ICA as the standard reference. Diagnostic accuracy was measured by the area under the curve (AUC), using ≥50% stenosis as the cut-off value.ResultsIn total, 134 target segments with severe calcification from 47 patients were analyzed. The mean specificity of conventional CCTA for each group ranged from 22.4 to 42.2%, which significantly improved with subtraction CCTA, ranging from 81.3 to 85.7% (all p < 0.001). The mean sensitivity of conventional CCTA for each group ranged from 83.3 to 88.0%. Following calcification subtraction, the mean sensitivity decreased for the novice (p < 0.001) and junior (p = 0.017) radiologists but was unchanged for the senior radiologists (p = 0.690). With subtraction CCTA, the mean AUCs of CCTA significantly increased: values ranged from 0.53, 0.54, and 0.61 to 0.70, 0.74, and 0.85 for the novice, junior, and senior groups (all p < 0.001).ConclusionSubtraction CCTA could improve the diagnostic accuracy of radiologists at all experience levels of CCTA interpretation.

Background: Most acute coronary syndromes occur due to coronary thrombosis caused by plaque rupture (PR) and plaque erosion (PE). Precise in vivo differentiation between PR and PE is challenging for intravascular imaging. This study is the first to determine the diagnostic performance of the novel 60 MHz high-definition intravascular ultrasound (HD-IVUS) for differentiating atherosclerotic plaque morphology influenced by local hemodynamic flow in rabbits. This study evaluated the diagnostic performance of 60 MHz HD-IVUS in identifying thrombosis in rabbits. Methods: We established 60 rabbit models of atherosclerosis with left common carotid artery (LCCA) stenosis and 30 FeCl3-induced LCCA thrombosis. Intravascular imaging was assessed with 60 MHz HD-IVUS and fourier-domain optical coherence tomography (FD-OCT). The present study investigated the diagnostic accuracy of 60 MHz HD-IVUS for PR and PE, as well as thrombosis, using OCT-diagnosis as a standard reference. Results: 60 MHz HD-IVUS for identifying atherosclerotic plaque morphology using plaque cavity and minor intimal irregularities showed high sensitivity and specificity; 92.0 and 90.0% for identifying OCT-defined PR, and 80.0 and 70.0% for OCT-defined PE, respectively. In a rabbit thrombus model, 60 MHz HD-IVUS showed high sensitivity (88.0%) and specificity (80.0%) in identifying OCT-defined thrombosis. Conclusions: 60 MHz HD-IVUS can accurately identify PR and thrombosis. Further studies should confirm the clinical value of this novel technique in PE diagnosis.

Background: Exploring the pharmacokinetic (PK) changes of various active components of single herbs and their combinations is necessary to elucidate the compatibility mechanism. However, the lack of chemical standards and low concentrations of multiple active ingredients in the biological matrix restrict PK studies. Methods: A putative multiple reaction monitoring strategy based on liquid chromatography coupled with mass spectrometry (LC–MS) was developed to extend the PK scopes of quantification without resorting to the use of chemical standards. First, the compounds studied, including components with available reference standard (ARS) and components lacking reference standard (LRS), were preclassified to several groups according to their chemical structures. Herb decoctions were then subjected to ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis with appropriate collision energy (CE) in MS2 mode. Finally, multiple reaction monitoring transitions transformed from MS2 of ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were used for ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry to obtain the mass responses of LRS components. LRS components quantification was further performed by developing an assistive group-dependent semiquantitative method. Results: The developed method was exemplified by the comparative PK process of single herbs Radix Ginseng (RG), Radix Polygala (RP), and their combinations (RG–RP). Significant changes in PK parameters were observed before and after combination. Conclusion: Results indicated that Traditional Chinese Medicine combinations can produce synergistic effects and diminish possible toxic effects, thereby reflecting the advantages of compatibility. The proposed strategy can solve the quantitative problem of LRS and extend the scopes of PK studies. Keywords: Herb–herb interactions, Liquid chromatography coupled with mass spectrometry, Pharmacokinetics study, Radix Ginseng, Radix Polygala

Background: Hepatocellular carcinoma (HCC) is a highly fatal malignant cancer worldwide. Elucidating the underlying molecular mechanism of HCC progression is critical for the identification of new therapeutic targets for HCC. This study aimed to determine the role of Non-SMC condensin II complex subunit G2 (NCAPG2) in HCC proliferation and metastasis. Methods: We detected NCAPG2 expression in tissues using immunohistochemistry, western blotting and real-time PCR. The effects of NCAPG2 on cell proliferation and metastasis were evaluated both in vitro and in vivo. Immunocytochemistry, enzyme linked immunosorbent assay, co-immunoprecipitation and luciferase reporter assay were performed to uncover the underlying mechanisms. Findings: We found that NCAPG2 is frequently upregulated in HCC tumour tissues and predicts a poor prognosis. NCAPG2 overexpression promotes HCC proliferation, migration, and invasion through activating STAT3 and NF-κB signalling pathways. Moreover, NCAPG2 is a direct target of miR-188-3p. We demonstrated the existence of a positive feedback loop between NCAPG2 and p-STAT3 and a negative feedback loop between NCAPG2 and miR-188-3p. Interpretation: Our study indicates that NCAPG2 overexpression could drive HCC proliferation and metastasis through activation of the STAT3 and NF-κB/miR-188-3p pathways. These findings may contribute to the identification of novel biomarkers and therapeutic targets for HCC. Fund: National Key Program for Science and Technology Research and Development (Grant No. 2016YFC0905902); the National Natural Scientific Foundation of China (Nos. 81772588, 81602058, 81773194); University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (Grant No. UNPYSCT-2016200); the Innovative Research Program for Graduate of Harbin Medical University (Grant Nos. YJSCX2017-38HYD, YJSCX2016-18HYD). Keywords: NCAPG2, Hepatocellular carcinoma, STAT3, NF-κB, miR-188-3p

We hereby review the perception and responses to the stress hormone Abscisic acid (ABA), along the trajectory of 500M years of plant evolution, whose understanding may resolve how plants acquired this signaling pathway essential for the colonization of land. ABA levels rise in response to abiotic stresses, coordinating physiological and metabolic responses, helping plants survive stressful environments. In land plants, ABA signaling cascade leads to growth arrest and large-scale changes in transcript levels, required for coping with environmental stressors. This response is regulated by a PYRABACTIN RESISTANCE 1-like (PYL)–PROTEIN PHOSPHATASE 2C (PP2C)–SNF1-RELATED PROTEIN KINASE 2 (SnRK2) module, that initiates phosphor-activation of transcription factors and ion channels. The enzymatic portions of this module (phosphatase and kinase) are functionally conserved from streptophyte algae to angiosperms, whereas the regulatory component –the PYL receptors, putatively evolved in the common ancestor of Zygnematophyceae and embryophyte as a constitutive, ABA-independent protein, further evolving into a ligand-activated receptor at the embryophyta. This evolutionary process peaked with the appearance of the strictly ABA-dependent subfamily III stress-triggered angiosperms' dimeric PYL receptors. The emerging picture is that the ancestor of land plants and its predecessors synthesized ABA, as its biosynthetic pathway is conserved between ancestral and current day algae. Despite this ability, it was only the common ancestor of land plants which acquired the hormonal-modulation of PYL activity by ABA. This raises several questions regarding both ABA's function in ABA-non-responsive organisms, and the evolutionary aspects of the ABA signal transduction pathway.

Abstract Natural killer (NK) cells represent a subset of lymphocytes that contribute to innate immunity and have been reported to play a role in autoimmune uveitis. However, the mechanisms regulating NK cellular function in this condition remain unclear. Herein, we investigated the status of NK cells in experimental autoimmune uveitis (EAU). We found that the number of CD83+CD3−NK1.1+ cells was increased in the inflamed eyes and spleens of the EAU mouse model. At the recovery stage of EAU, serum concentrations of soluble CD83 (sCD83) were increased. sCD83 treatment relieved retinal tissue damage and decreased the number of infiltrating NK cells in inflamed eyes. Further analysis of the effects of sCD83 treatment in EAU revealed that it reduced: 1) the expressions of CD11b and CD83 in NK cells, 2) the percent of CD11bhighCD27lowCD3−NK1.1+ cells and 3) the secretion of granzyme B, perforin and IFN-γ in NK cells as demonstrated both in vivo and in vitro. When sCD83 treated-NK cells were transferred into EAU mice, retinal tissue damage was relieved. These results demonstrate sCD83 down-regulate NK cellular function and thus provide important, new information regarding the means for the beneficial effects of this agent in the treatment of autoimmune uveitis.

The entrance and exit sections of a tunnel are the accident black-spots in an expressway. For a safe operation of road tunnels, it is necessary to understand a driver's physiological indices and driving performance when driving through tunnels. In this study, the UC-Win/Road simulation software was used to build 12 tunnel models of different lengths. A simulated driving experiment was carried out in a 6-DoF motion platform. The lateral position of vehicles characterizing the driving performance was measured using the motion platform. Electrocardiogram and eye movement data of 25 recruited drivers were collected simultaneously through the experiment. The spatial changes in a driver's heart rate (HR) growth rate, RMSSD, pupil diameter growth rate and vehicle lateral deviation within 300 m before and after the tunnel entrance and exit were analyzed to determine the variation rules in the different tunnels. The study identified the length range in the tunnel entrance and exit sections that influences the drivers. A quantitative analysis was further carried out to analyze the relationship between the physiological indices and the driving performance indicator. The results showed that a driver's heart rate fluctuates significantly 250 m before the tunnel entrance and 50 m before the exit. In this region, the pupil diameter increases gradually, and drivers tend to shift the vehicle to the left. At the tunnel exit, the HR and RMSSD are affected significantly by the tunnel length, and the variation is higher in longer tunnels. In comparison, the tunnel length has no significant effect on the physiological indicators and driving performance of the drivers at the entrance and exit.

To reduce the impact of acoustic interference in a microelectromechanical system (MEMS) gyroscope and to improve the reliability of output data, a filtering algorithm based on orthogonal demodulation is proposed. According to the working principle and failure mechanism of a MEMS gyroscope, the sound and angular velocity frequencies are not identical, which lead to a different frequency signal output of the original single-channel demodulation scheme. Therefore, a Q channel demodulation filtering process was added to the origin single-channel demodulation scheme. For the Q channel demodulated signal, a Hilbert transform was used to compensate for the 90 degree phase shift. The IQ dual-channel difference can remove the acoustic interference signal. The simulation results indicate that the scheme can effectively suppress the acoustic interference signal and it can eliminate more than 95% of the impact of sound waves. We assembled the acoustic interference experimental platform, collected the driving and sensing data, and verified the denoising performance with our algorithm, which eliminated more than 70% of the noise signal. The simulation and experimental results demonstrate that the scheme can eliminate acoustic interference signal without destroying angular velocity signal.

The age of space electric propulsion arrived and found the space exploration endeavors at a paradigm shift in the context of new space. Mega-constellations of small satellites on low-Earth orbit (LEO) are proposed by many emerging commercial actors. Naturally, the boom in the small satellite market drives the necessity of propulsion systems that are both power and fuel efficient and accommodate small form-factors. Most of the existing electric propulsion technologies have reached the maturity level and can be the prime choices to enable mission versatility for small satellite platforms in Earth orbit and beyond. At the Plasma Sources and Applications Centre/Space Propulsion Centre (PSAC/SPC) Singapore, a continuous effort was dedicated to the development of low-power electric propulsion systems that can meet the small satellites market requirements. This review presents the recent progress in the field of electric propulsion at PSAC/SPC Singapore, from Hall thrusters and thermionic cathodes research to more ambitious devices such as the rotamak-like plasma thruster. On top of that, a review of the existing vacuum facilities and plasma diagnostics used for electric propulsion testing and characterization is included in the present research.

Van der Waals heterojunctions based on transition metal dichalcogenides (TMDs) show promising potential in optoelectronic devices, due to the ultrafast separation of photoexcited carriers and efficient generation of the photocurrent. Herein, this study demonstrated a high-responsivity photovoltaic photodetector based on a MoTe2/MoSe2 type-II heterojunction. Due to the interlayer built-in potential, the MoTe2/MoSe2 heterojunction shows obvious photovoltaic behavior and its photoresponse can be tuned by the gate voltage due to the ultrathin thickness of the heterojunction. This self-powered photovoltaic photodetector exhibits an excellent responsivity of 1.5 A W−1, larger than previously reported TMDs-based photovoltaic photodetectors. Due to the high-efficiency separation of electron-hole pairs and ultrafast charge transfer, the light-induced on/off ratio of current switching is larger than 104 at zero bias, and the dark current is extremely low (~10−13 A). These MoTe2/MoSe2 type-II heterojunctions are expected to provide more opportunities for future nanoscale optoelectronic devices.