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Simulation and optimization methods have been widely used in forklift design due to their cost-effectiveness. However, this type of method involves challenges such as the accuracy of the simulation model and the simulation solution time. These challenges reduce the stability and precision of the surrogate model and hence generate further optimization errors. In this paper, a multi-objective surrogate modeling (MSM) method for telescopic boom forklifts based on closed-loop transfer learning is proposed in order to solve these challenges. The MSM consists of the following two steps: to pre-train an initial deep neural network model (deep model) with a large amount of existing simulation data from the same type of forklift and to transfer the model with a small amount of measurement data collected on the current forklift. A general framework for deep neural network (DNN) training is introduced to improve the approximation ability of the initial model. Moreover, a novel uncertainty-analysis-based sampling method is suggested for measurement data development, and combined with transfer learning to form a closed-loop mode to improve the stability of the final model. The superiority of MSM is demonstrated through comparative studies with the fine-tuning method on a telescopic boom forklift with two objectives. The experimental results show that the Correlation coefficient (R) of the deep model can reach 0.9971 by using only 80 sets of training data. In addition, it can also achieve an improvement of at least a 13.25% reduction in Root Mean Squared Error (RMSE) and a 9.19% reduction on average in Maximum Absolute Error (MAE), as well as stronger robustness compared to the benchmarks. Furthermore, it will provide a valuable reference for the simulation optimization of complex electromechanical products.

Abstract Background Stressful life events (SLEs) and adverse childhood experiences (ACEs) have been reported to be associated with perinatal depression (PND) or perinatal anxiety (PNA) alone; however, in most cases, majority of PND and PNA coexist and could lead to more serious health consequences. The independent effect of recent SLEs and their joint effects with ACEs on perinatal comorbid anxiety and depression (CAD) remain inadequately explored. Methods Based on a longitudinal study, 1082 participants receiving prenatal care in Ma’anshan, China were included. Women were recruited in the first trimester (T1: ≤14+ 6 weeks) and followed up at 15 ~ 27 weeks (T2), 28 ~ 40 weeks (T3), and postpartum (T4). Depression and anxiety status were assessed at all time points, while recent SLEs and ACEs were measured at T1. Logistic regression was conducted to examine the associations of SLEs with the risks of CAD at different time points, as well as their joint effects with ACEs on CAD. Results Approximately 38.5% of women experienced at least one SLE, which was significantly associated with higher risks of CAD at all time points (p

Background: A key challenge in the understanding and treatment of depression is identifying cell types and molecular mechanisms that mediate behavioral responses to antidepressant drugs. Because treatment responses in clinical depression are heterogeneous, it is crucial to examine treatment responders and nonresponders in preclinical studies. Methods: We used the large variance in behavioral responses to long-term treatment with multiple classes of antidepressant drugs in different inbred mouse strains and classified the mice into responders and nonresponders based on their response in the forced swim test. Medial prefrontal cortex tissues were subjected to RNA sequencing to identify molecules that are consistently associated across antidepressant responders. We developed and used virus-mediated gene transfer to induce the gene of interest in specific cell types and performed forced swim, sucrose preference, social interaction, and open field tests to investigate antidepressant-like and anxiety-like behaviors. Results: Cartpt expression was consistently upregulated in responders to four types of antidepressants but not in nonresponders in different mice strains. Responder mice given a single dose of ketamine, a fast-acting non–monoamine-based antidepressant, exhibited high CART peptide expression. CART peptide overexpression in the GABAergic (gamma-aminobutyric acidergic) neurons of the anterior cingulate cortex led to antidepressant-like behavior and drove chronic stress resiliency independently of mouse genetic background. Conclusions: These data demonstrate that activation of CART peptide signaling in GABAergic neurons of the anterior cingulate cortex is a common molecular mechanism across antidepressant responders and that this pathway also drives stress resilience.

Abstract Background Joint Awareness is thought to be closely linked to Quality of Life (QoL) for patients undergoing Total Knee Arthroplasty (TKA), yet to date there have been no longitudinal studies to explore how Joint Awareness actually affects QoL. The purpose of this study was therefore to examine the development of Joint Awareness and QoL after TKA as well as the dynamic impact of Joint Awareness on QoL. Methods A total of 342 patients were followed up at 3 months (T1), 6 months (T2), and 12 months (T3) after TKA. Joint Awareness was evaluated using the Forgotten Joint Score-12 (FJS-12), and QoL was measured by SF-36. We used repeated measures analysis of variance to estimate the development of Joint Awareness and QoL and employed a cross-lagged model to examine the dynamic relationship between Joint Awareness and QoL. Results Both Joint Awareness and QoL improved with postoperative time (p

Abstract Ceruloplasmin (CP) plays an important role in maintaining iron homeostasis. Cp gene knockout (Cp -/- ) mice develop a neurodegenerative disease with aging and show iron accumulation in the brain. However, iron deficiency has also been observed in 3 M Cp -/- mice. The use of systemic Cp gene knockout is insufficient to reveal specific functions for CP in the central nervous system. Considering recent discoveries that astrocytes synthetize the majority of brain CP, we generated astrocyte conditional Cp knockout (Cp Gfap cKO) mice, and found that iron contents decreased in the cerebral cortex and hippocampus of young (6 M) and old (18 M) Cp Gfap cKO mice. Further experiments revealed that 6 M Cp Gfap cKO mice exhibited impaired learning and memory function, while 18 M Cp Gfap cKO mice exhibited improved learning and memory function. Our study demonstrates that astrocytic Cp deletion blocks brain iron influx through the blood-brain-barrier, with concomitantly increased iron levels in brain microvascular endothelial cells, resulting in brain iron deficiency and down-regulation of ferritin levels in neurons, astrocytes, microglia and oligodendrocytes. At the young age, the synapse density, synapse-related protein levels, 5-hydroxytryptamine and norepinephrine, hippocampal neurogenesis and myelin formation were all decreased in Cp Gfap cKO mice. These changes affected learning and memory impairment in young Cp Gfap cKO mice. In old Cp Gfap cKO mice, iron accumulation with aging was attenuated, and was accompanied by the alleviation of the ROS-MAPK-apoptosis pathway, Tau phosphorylation and β-amyloid aggregation, thus delaying age-related memory decline. Overall, our results demonstrate that astrocytic Cp deletion has divergent effects on learning and memory function via different regulatory mechanisms induced by decreased iron contents in the brain of mice, which may present strategies for the prevention and treatment of dementia.

Electricity is the foundation of the entire national economy, and nuclear power has become an important part of the power system with its unique advantages. The main process of nuclear power is the process of the nuclear fuel cycle, including the source and preparation of nuclear fuel, nuclear power plants and nuclear spent fuel processing. In the whole process, nuclear safety is the top priority and the key to the sustainable development of nuclear power. In this paper, aiming at the objective reality of high security risk and strict security requirements for nuclear fuel storage used in nuclear power, based on the analysis of nuclear fuel radiation characteristics and safety monitoring requirements, a nuclear fuel embedded system is designed from the aspects of system overall, software, hardware, data processing, etc. Security intelligent monitoring system. The system uses MCU as the control core, is equipped with motion detection and electronic seal devices, and realizes alarm functions such as identity authentication, unauthorized movement, and illegal unpacking real-time monitoring. Experiments and use show that the system can be easily integrated, installed and deployed on the nuclear fuel packaging container, and the operation is stable and reliable, which effectively promotes the steady improvement of the operating efficiency and operating quality of the nuclear energy system.

Tumor derived small extracellular vesicles (TsEVs) display a great potential as efficient nanocarriers for chemotherapy because of their intrinsic targeting ability. However, the inherited risks of their original cargos (like loaded proteins or RNAs) from parent cancer cells in tumor progression severely hinder the practical application. In this study, a saponin-mediated cargo elimination strategy was established and practiced in glioblastoma (GBM) cell-derived small extracellular vesicles (GBM-sEVs). A high eliminating efficacy of the cargo molecules was confirmed by systematic analysis of the original proteins and RNAs in GBM-sEVs. In addition, the inherited functions of GBM-sEVs to promote GBM progression vanished after saponin treatment. Moreover, the results of cellular uptake analysis and in vivo imaging analysis demonstrated that saponin treatment preserved the homotypic targeting ability of GBM-sEVs. Thus, we developed an efficient nanocarrier with improved biosafety for GBM suppression. Furthermore, doxorubicin (DOX) transported by the saponin-treated GBM-sEVs (sa-GBM-sEVs) displayed an effective tumor suppression in both subcutaneous and orthotopic GBM models of mouse. Collectively, this study provides a feasible way to avoid the potential protumoral risks of TsEVs and can advance the clinical application of TsEVs in chemotherapy.

Methyl methacrylate (MMA) has emerged as an essential industrial monomer. However, the toxic by-production and shortage supply of MMA in the global market has gained great attention. Herein, a one-step synthesis to produce MMA from isobutene via a direct oxidative esterification process has been demonstrated to curb the aforementioned downsides. Thermodynamic analysis via Gibbs free energy minimization method proved the feasibility of this route via the equilibrium constant. Despite tert-butanol and isobutane showed higher equilibrium constant than isobutene, they should be avoided. Isobutane is highly flammable while the precursor of tert-butanol is exorbitant. Thus, isobutene was selected for the equilibrium compositions screening. Isobutene conversion was 90% and 15% MMA yield at 700 °C and IBN: O2: MeOH ratio with 1:7:1. This route is mainly limited by the generation of side reactions from the reaction of CH3OH and O2. By varying the feedstock ratio at 1:2:1, the MMA yield increased to ~25%. Copyright © 2022 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

The bioecological characteristics of plants determine their status and role in the community. The advantages of dominant species in the community compared with companion species in terms of physiological and ecological characteristics remain unclear. When both dominant and companion species in grassland plant communities are clonal, these plants are able to share resources within clones (physiological integration). However, it is unclear how the clonal dominant and companion species differ in the effect of their physiological integration on sexual reproduction. We chose Leymus chinensis, the dominant species of the most widespread meadow plant communities in the semiarid and arid regions of northern China, and its main companion species L. secalinus, Calamagrostis ripidula, C. pseudophragmites, and C. epigeios and conducted a series of in situ field experiments in a homogeneous environment, including the determination of the phenotypic characteristics of reproductive ramets with connected (allowing physiological integration) and disconnected (preventing integration) tillering nodes for each species, as well as 15N leaf labeling of ramet pairs at the milk-ripe stage. In the clonal populations of the five grasses, physiological integration between vegetative ramets and reproductive ramets interconnected by tillering nodes significantly increased the leaf, stem, inflorescence and ramet biomasses of reproductive ramets, and relative changes in ramet biomass were greatest in L. chinensis. 15N labeling showed that vegetative ramets supplied nutrients to reproductive ramets through tillering nodes; the amount of translocated 15N per unit of reproductive ramet biomass was highest in L. chinensis. Overall, our results indicate that in the five clonal grasses, physiological integration between functionally different ramets under tillering node connections had a significant positive effect on sexual reproduction, indicating interspecific consistency in the contribution of physiological integration to sexual reproduction between the dominant and companion species, but this positive effect was greater in the dominant species L. chinensis than in the four main companion species. Therefore, differences in the physiological integration ability between the dominant and main companion species, identified for the first time in this study, may explain, at least partly, the dominance of L. chinensis in the community.

Abstract Resolving inflammation and promoting intestinal tissue regeneration are critical for inflammatory bowel disease (IBD) treatment. Bioactive glass (BG) is a clinically approved bone graft material and has been shown to modulate inflammatory response, but it is unknown whether BG can be applied to treat IBD. Here, it is reported that BG attenuates pro‐inflammatory response of lipopolysaccharide (LPS)‐stimulated macrophages and hence reduces inflammatory damage to intestinal organoids in vitro. In addition, zein/sodium alginate‐based core–shell microspheres (Zein/SA/BG) are developed for oral delivery of BG, which helps prevent premature dissolution of BG in the stomach. The results show that Zein/SA/BG protects BG from a gastric‐simulated environment while dissolved in an intestinal‐simulated environment. When administered to acute and chronic colitis mice model, Zein/SA/BG significantly reduces intestinal inflammation, promotes epithelial tissue regeneration, and partially restores microbiota homeostasis. These findings are the first to reveal the therapeutic efficacy of BG against IBD, which may provide a new therapeutic approach at low cost for effective IBD treatment.

Background: Studies have identified patients’ beliefs about medicines as an important determinant of non-adherence. However, scant data are available on the possible association between patients’ beliefs and statin non-adherence among adult patients in China. The objectives of this study are to assess the prevalence of statin non-adherence, and to identify the factors associated with statin non-adherence, especially the association between inpatients’ beliefs about statins and non-adherence in a tertiary hospital in the Northwestern China.Methods: A cross-sectional questionnaire-based survey was carried out in the department of cardiology and neurology between February and June 2022. The Beliefs about Medicine Questionnaire (BMQ) was used to assess patients’ beliefs about statins. The Adherence to Refills and Medications Scale (ARMS) was used to assess statin adherence. Logistic regression analyses were performed to identify the factors associated with statin non-adherence. Receiver operator characteristic (ROC) was conducted to assess the performance of the logistic regression model in predicting statin non-adherence.Results: A total of 524 inpatients participated and finished the questionnaire, 426 (81.3%) inpatients were non-adherent to statin, and 229 (43.7%) inpatients expressed strong beliefs about the stain treatment necessity, while 246 (47.0%) inpatients expressed strong concerns about the potential negative effects. We found that the low necessity beliefs about statin (adjusted odds ratio [OR] and 95% confidence interval [CI], 1.607 [1.019, 2.532]; p = 0.041), prescribed rosuvastatin (adjusted OR 1.820 [1.124, 2.948]; p = 0.015) and ex-drinker (adjusted OR 0.254 [0.104, 0.620]; p = 0.003) were independent determinants of statin non-adherence.Conclusion: Statin adherence was poor in this study. The findings indicated a significant association between inpatients’ lower necessity beliefs and statin non-adherence. More attention should be focused on statin non-adherence in China. Nurses and pharmacists could play an important role in patient education and patient counseling in order to improve medication adherence.

Lanzhou lily (Lilium davidii var. unicolor) is a renowned edible crop produced in China and relatively sensitive to high temperature (HT). Trichokonins (TKs) are antimicrobial peptaibols secreted from Trichoderma longibrachiatum strain SMF2. Here, we report that TKs application improves the thermotolerance of Lanzhou lily. The activity of the antioxidant enzyme system (SOD, CAT, and POD), the level of heat-resistance-associated phytohormones (ABA, SA, and JA), the relative water content (RWC), the content of chlorophyll (Chl), and the net photosynthetic rate (Pn) were promoted by TKs treatment in Lanzhou lily plants subjected to heat stress (HS). TKs treatment also mitigated cell injury as shown by a lower accumulation of malondialdehyde (MDA) and relative electrolyte leakage (REL) under HS conditions. RNA-seq data analysis showed that more than 4.5 times differentially expressed genes (DEGs) responded to TKs treatment under HS compared to non-HS, and TKs treatment reduced protein folding and enhanced cellular repair function under HS conditions. The analyses of DEGs involved in hormone (ABA, SA and JA) synthesis and signaling pathways suggested that TKs might improve Lanzhou lily heat tolerance by promoting ABA synthesis and signal transduction. TKs highly induced DEGs of the HSF-HSP pathway under HS, in which HSFA2 accounted for most of the HSF family. Furthermore, TKs treatment resulted in the upregulation of heat-protective genes LzDREB2B, LzHsfA2a, LzMBF1c, LzHsp90, and LzHsp70 involved in HSF-HSP signal pathway after long-term HS. LzHsfA2a-1 likely plays a key role in acquisition of TKs-induced thermotolerance of Lanzhou lily as evidenced by the sustained response to HS, the enhanced response to TKs treatment under long-term HS, and the high sequence similarity to LlHsfA2a which is a key regulator for the improvement of heat tolerance in Lilium longiflorum. Our results reveal the underlying mechanisms of TKs-mediated thermotolerance in Lanzhou lily and highlight an attractive approach to protecting crop plants from damage caused by HS in a global warming future.

IntroductionGlyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an essential key enzyme in the glycolytic pathway and plays an important role in stress responses. Although GAPDH family genes have been found in different plant species, the determination of their gene family analysis and their functional roles in soybean are still unknown. MethodsIn this study, gene sequence and expression data were obtained using online tools, and systematic evolution, expression profile analysis, and qRT-PCR analysis were conducted.Results and DiscussionHere a total of 16 GmGAPDH genes were identified on nine chromosomes, which were classified into three clusters. Additionally, all GmGAPDH genes harbor two highly conserved domains, including Gp_dh_N (PF00044) and Gp_dh_C (PF02800). The qRTPCR analysis also showed that most GmGAPDH genes significantly responded to multiple abiotic stresses, including NaHCO3, polyethylene glycol, cold, and salt. Among them, GmGAPDH14 was extraordinarily induced by salt stress. The GmGAPDH14 gene was cloned and overexpressed through soybean hair roots. The overexpressed transgenic soybean plants of the GmGAPDH14 gene have also shown better growth than that of control plants. Moreover, the overexpressed transgenic plants of GmGAPDH14 gene had higher activities of superoxide dismutase but lower malonaldehyde (MDA) content than those of control plants under salt stress. Meanwhile, a total of four haplotypes were found for the GmGAPDH14 gene, and haplotypes 2, 3, and 4 were beneficial for the tolerance of soybean to salt stress. These results suggest that the GmGAPDH14 gene might be involved in the process of soybean tolerance to salt stress. The results of this study will be valuable in understanding the role of GAPDH genes in the abiotic stress response of soybean.

The Chinese yam, an important orphan crop with both high nutrient and health promoting value, is mainly produced in the Yellow-Huai-Hai plain near the river basins in China. The protected designation of origin (PDO)-labeled Chinese yam differs greatly from others in market acceptance and price, which has led to fakes and the need for reliable authentication methods. Hence, stable isotope ratios of δ13C, δ15N, δ2D, and δ18O and 44 multielemental contents were used to explore the authentication of geographical origins and the effect of environmental factors. Twenty-two elements and δ15N were selected as the key variables to authenticate Chinese yams from three river basins as well as to authenticate them among traditional PDOs and others in the Yellow River basin. Moreover, six environmental factors, including the moisture index, maximum temperature, photosynthetically active radiation, soil organic carbon, total nitrogen and pH, were found to be highly related to these variances.

In 2022, persistent extreme precipitation events occurred during the Dragon Boat Water (DBW) period (May to June) over South China, with rainfall-breaking historical extremes at many stations. In this study, the relative importance of the thermodynamic and dynamic effects on this anomalous event was explored through budget equations of moisture and moist static energy (MSE). The moisture budget analysis suggests that the thermodynamic effect contributes to the precipitation anomaly by less than 10% through the advection of abnormal moisture by mean horizontal and vertical motion. However, the dynamic effect, associated with the mean moisture advection by anomalous vertical motion, makes the largest contribution. This seems to imply that the increase in water vapor due to global warming does not play a critical role in this extreme event. Nevertheless, further analysis of the MSE budget equation reveals that the anomalous vertical motion is governed by both the dynamical effect of atmospheric circulation changes and the thermodynamic effect of atmospheric thermal state changes. The thermodynamic effect, which accounts for 47.21% of the total effect (sum of the thermodynamic and dynamic effects), is caused by anomalous moist enthalpy (mainly dry enthalpy) advection due to the mean horizontal motion. In contrast, the dynamical effect is related to the warm and humid air advection caused by the anomalous southwest wind caused by the anomalous anticyclone over the northwest Pacific. Simultaneously, the anomalous northeast wind brings dry cold air, resulting in the convergence of cold and warm air over the Pearl River basin and persistent heavy rainfall events. The results of this study provide valuable insights into the direct and indirect physical mechanisms leading to anomalous DBW period over South China in 2022.

Ginkgo (Ginkgo biloba L.) is a cherished relic among plants, commonly planted as a street tree. However, it faces cultivation challenges due to escalating soil salinization and widespread snowmelt application. Therefore, this study used 4-year-old Ginkgo seedlings to investigate how exogenous melatonin at varying concentrations affects seedling growth and physiology under salinity stress. The results revealed that appropriate melatonin concentrations (0.02, 0.1 mmol·L−1) significantly mitigated leaf yellowing under different NaCl stress levels. Furthermore, they increased ground diameter, current-year branch growth, relative water concentration, free proline, and soluble sugars in leaves. Melatonin also reduced electrolyte exudation rates, flavonoids, and malonic dialdehyde concentration, while enhancing peroxidase and superoxide dismutase activities. This led to reduced chlorophyll content, photosynthetic rate, stomatal conductance, and transpiration rate, stabilizing intercellular CO2 concentration, preserving photosynthetic structures, and enhancing photosynthetic rates. Additionally, the decline in the photosynthetic electron transport rate, the effective photochemical quantum yield of PSII, and the potential efficiency of primary conversion of light energy of PSII was alleviated. Minimal fluorescence and the non-photochemical quenching coefficient also improved. However, high melatonin concentration (0.5 mmol·L−1) exacerbated salinity stress. After analyzing composite scores, the 0.02 mmol·L−1 melatonin treatment was most effective in alleviating NaCl stress, while the 0.5 mmol·L−1 treatment intensified physiological stress under 200 mmol·L−1 NaCl stress. Principal component analysis and correlation analysis identified seven physiological indicators (photosynthetic rate, transpiration rate, photosynthetic electron transport rate, minimal fluorescence, superoxide dismutase, free proline, and chlorophyll a) and three growth indicators (ground diameter, branch length, and current-year branch thickness) as key markers for rapid salinity stress assessment in Ginkgo. These findings are crucial for addressing challenges associated with snowmelt’s impact on roadside Ginkgo trees, expanding planting areas, and breeding exceptional salt-tolerant Ginkgo varieties.

To improve the classification of pig vocalization using vocal signals and improve recognition accuracy, a pig vocalization classification method based on multi-feature fusion is proposed in this study. With the typical vocalization of pigs in large-scale breeding houses as the research object, short-time energy, frequency centroid, formant frequency and first-order difference, and Mel frequency cepstral coefficient and first-order difference were extracted as the fusion features. These fusion features were improved using principal component analysis. A pig vocalization classification model with a BP neural network optimized based on the genetic algorithm was constructed. The results showed that using the improved features to recognize pig grunting, squealing, and coughing, the average recognition accuracy was 93.2%; the recognition precisions were 87.9%, 98.1%, and 92.7%, respectively, with an average of 92.9%; and the recognition recalls were 92.0%, 99.1%, and 87.4%, respectively, with an average of 92.8%, which indicated that the proposed pig vocalization classification method had good recognition precision and recall, and could provide a reference for pig vocalization information feedback and automatic recognition.

Anthurium andraeanum Linden is a prominent ornamental plant belonging to the family Araceae and is cultivated worldwide. The morphology characteristics are crucial because they significantly impact ornamental values, commercial properties, and the efficiency of space utilization in production. However, only a few related investigations have been conducted in anthurium to date. In this study, an F1 genetic segregation population containing 160 progenies was generated through hybridization between potted and cut anthurium varieties. Fifteen morphological traits were assessed and revealed substantial levels of genetic variation and widespread positive correlation. Based on specific length amplified fragment (SLAF) sequencing technology, 8171 single nucleotide polymorphism (SNP) markers were developed, and the high-density linkage map of 2202.27 cM in length distributed on 15 linkage groups was constructed successfully, with an average distance of 0.30 cM. Using the inclusive composite interval mapping (ICIM) method, 59 QTLs related to 15 key morphological traits were successfully identified, which explained phenotypic variance (PVE) ranging from 6.21% to 17.74%. Thirty-three of those associated with 13 traits were designated as major QTLs with PVE > 10%. These findings offer valuable insights into the genetic basis of quantitative traits and are beneficial for molecular marker-assisted selection (MAS) in anthurium breeding.

Wind and solar energy resources show a daily and seasonal fluctuation trend， which puts high pressure on grid dispatching and has become a huge problem that hinders the connection of clean energy to the grid.Based on the whole year measured data of adjacent wind farms and photovoltaic power stations in the west of Jilin， this paper selected coefficient of variation as the metrics， to investigate the stability of transmitted power of the two resources under different utilization ratios， and analyzed their complementary nature from the perspective of diurnal variation and monthly variation.Three typical correlation indexes， Pearson correlation coefficient， Spearman’s rank correlation coefficient and Kendall’s rank correlation coefficient， were used to illustrate the rationality of the stability indexes.The results showed that the diurnal variation of wind and solar resources is more complementary than the monthly variation， and the stability of superimposed resources can be greatly improved by adjusting the utilization ratio of certain resources.In this paper， an measurement of the complementarity of wind and solar energy resources is established based on measured data of a single year in one region.The research conclusions can provide references for dispatching the two kinds of resources simultaneously.

Abstract Background NLRP3 inflammasome activation and pyroptosis play a significant role in myocardial ischemia reperfusion injury (MI/RI). Geniposide was reported to show potential therapeutic use for MI/RI with its anti-inflammatory and anti-oxidative properties. However, research on the specific mechanism of geniposide has not been reported. Methods The MIRI model of animal was created in male C57BL/6J mice and the hypoxia reoxygenation (H/R) model was established for the in vitro experiments. Neonatal rat ventricular myocytes (NRVMs) and H9c2 cells with knockdown of TXNIP or NLRP3 were used. Geniposide was administered to mice before vascular ligation. HE staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, echocardiography, oxidative stress and myocardial enzyme detection were used to evaluate the cardioprotective effect of geniposide. Meanwhile, pharmacological approaches of agonist and inhibitor were used to observe potential pathway for geniposide cardioprotective in vitro and in vivo. Moreover, ELISA kits were adopted to detect the levels of inflammatory factors, such as IL-1β and IL-18. The gene and protein expression of NLRP3 and pyroptosis-related factors in heart tissue were performed by RT-PCR, western blotting and immunofluorescence in vivo and in vitro, respectively. Results Our results indicate that geniposide can reduce the area of myocardial infarction, improve heart function, and inhibit the inflammatory response in mice after MI/RI. In addition, RT-PCR and western blotting shown geniposide promoting AMPK phosphorylation to activate myocardium energy metabolism and reducing the levels of genes and proteins expression of NLRP3, ASC, N-GSDMD and cleaved caspase-1, IL-1β, IL-18. Meanwhile, geniposide improved NRVMs energy metabolism, which decreased ROS levels and the protein expression of TXNIP and thus suppressed the expression of NLRP3. AMPK antagonist or agonist and siRNA downregulation of TXNIP or NLRP3 were also verify the effect of geniposide against H/R injury. Further research found that geniposide promoted the translocation of TXNIP and reduce the binding of TXNIP and NLRP3. Conclusions In our study, geniposide can significantly inhibit NLRP3 inflammasome activation via the AMPK signaling pathway and inhibit pyroptosis of cardiomyocytes in myocardial tissues.

Abstract Background Constructivism theory has suggested that constructing students’ own meaning is essential to successful learning. The erroneous example can easily trigger learners’ confusion and metacognition, which may “force” students to process the learning material and construct meaning deeply. However, some learners exhibit a low level of elaboration activity and spend little time on each example. Providing instructional scaffolding and elaboration training may be an efficient method for addressing this issue. The current study conducted a randomized controlled trial to examine the effectiveness of erroneous example elaboration training on learning outcomes and the mediating effects of metacognitive load for Chinese students in medical statistics during the COVID-19 pandemic. Methods Ninety-one third-year undergraduate medical students were randomly assigned to the training group (n = 47) and the control group (n = 44). Prerequisite course performance and learning motivation were collected as covariates. The mid-term exam and final exam were viewed as posttest and delayed-test to make sure the robustness of the training effect. The metacognitive load was measured as a mediating variable to explain the relationship between the training and academic performance. Results The training significantly improved both posttest and delayed-test performance compared with no training (F posttest = 26.65, p

Abstract Background Neuroinflammation-induced injury is intimately associated with poor prognosis in patients with cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase–stimulator of interferon gene (cGAS–STING) axis is a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as a crucial mediator of neuroinflammation in ischemic stroke. However, the role of the cGAS–STING pathway in modulating post-CVST inflammation and the underlying mechanisms involved remain unclear. Methods A CVST model was induced by ferric chloride in male C57BL/6J mice. The selective cGAS inhibitor RU.521, STING agonist 2′3′-cGAMP, and STING siRNA were delivered by intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C staining, dihydroethidium staining, western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA and flow cytometry. Results cGAS, STING, NLRP3 and GSDMD were significantly upregulated after CVST and mostly in the microglia of the mouse brain. CVST triggered the release of dsDNA into the cytoplasm and elicited an inflammatory response via activating the cGAS–STING axis. RU.521 decreased the levels of 2′3′-cGAMP, STING and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- and cleaved IL-1β, and cleaved IL-1β/pro-IL-1β. Besides, RU.521 treatment also reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration along with neurological deficits post-CVST. 2′3'-cGAMP delivery enhanced the expressions of STING and related inflammatory mediators, NLRP3 inflammasome and pyroptosis-relevant proteins, whereas these alterations were significantly abrogated by the silencing of STING by siRNA. Conclusions Our data demonstrate that repression of the cGAS–STING pathway diminishes the neuroinflammatory burden of CVST and highlight this approach as a potential therapeutic tactic in CVST-mediated pathologies.

The small GTPase ADP-ribosylation factor 6 (ARF6) mediates chemokine (C-C motif) ligand 18 (CCL18)-induced activation of breast cancer (BC) metastasis through its downstream effector AMAP1. However, the molecular mechanisms underlying CCL18 up-regulating ARF6 remain largely unclear. Here, microRNAs (miRNAs) that target ARF6 were predicted and selected in high metastatic BC cells treated with CCL18. Next, we assessed the role of exosomal miR-760 in vitro and in vivo. We further analyzed the expression of ARF6, AMAP1, and phosphorylated (p)-AMAP1 in tumor and adjacent normal tissues. We first observed that CCL18 increased the expression of ARF6 and p-AMAP1 and activated the Src/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. ARF6 knockdown significantly impaired CCL18-induced malignant cellular behaviors and the Src/PI3K/Akt signaling pathway. Next, ARF6 was confirmed as a target gene of miR-760 in exosomes derived from CCL18-stimulated high metastatic BC cells. Moreover, recipient MCF-7 cells could effectively uptake these miR-760-rich exosomes that significantly promoted proliferation, tumor growth in vivo, migration, invasion, and chemoresistance by activating ARF6-mediated Src/PI3K/Akt signaling and the epithelial-mesenchymal transition (EMT) pathway. Together, our results support that exosomal miR-760 secreted by CCL18-stimulated high metastatic BC cells promoted the malignant behaviors in low metastatic BC cells by up-regulating the ARF6-mediated Src/PI3K/Akt signaling pathway.

Introduction The management of perinatal depression (PND) is challenging in China. The Thinking Healthy Programme (THP), developed under the core theory of cognitive–behavioural therapy, is an evidence-based approach that is recommended as a psychosocial intervention for managing PND in low/middle-income countries. Sparse evidence has been generated, however, to assess the effectiveness of THP and guide its implementation in China.Methods and analysis A hybrid type II effectiveness–implementation study is ongoing in four cities in Anhui Province, China. A comprehensive online platform, Mom’s Good Mood (MGM), has been developed. Perinatal women are screened using the WeChat screening tool (ie, Edinburgh Postnatal Depression Scale embedded as metrics) in clinics. Different intensities of the intervention are delivered through the mobile application for different degrees of depression, according to the stratified care model. The THP WHO treatment manual has been tailored to be the core component of intervention. Guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, process evaluations will be conducted to identify the facilitators and barriers to implementation and to modify the implementation strategy; summative evaluations will be carried out to examine the effectiveness of MGM in the management of PND within the primary healthcare system in China.Ethics and dissemination Ethics approval and consent for this programme were obtained from Institutional Review Boards in China: Anhui Medical University, Hefei, People’s Republic of China (20170358). Results will be submitted to relevant conferences and peer-reviewed journals.Trial registration number ChiCTR1800016844.

Abstract The drift history of the Lhasa terrane is crucial for understanding the tectonic evolution of Tethyan Oceans and Jurassic true polar wander. However, high‐quality Middle Jurassic paleomagnetic data from the Lhasa terrane are limited in number. Here we report a combined paleomagnetic and geochronologic study on the Yeba Formation volcanic rocks, dated at ∼170 Ma, from the Lhasa terrane. Robust field and reversal tests indicate that the characteristic remanent magnetizations are primary. Our results provide a reliable Middle Jurassic (∼170 Ma) paleopole at 29.8°N, 180.7°E with A95 = 5.7° and a paleolatitude of 14.4 ± 5.7°N for the Lhasa area. Compared with previous paleomagnetic and geologic evidence, we propose that the Meso‐Tethys Ocean probably began to close in the eastern part at ∼168 Ma and that the Lhasa terrane underwent a ∼2,900 km southward “monster shift” during the Late Jurassic.

Abstract Small extracellular vesicles derived from human pluripotent stem cells (hPSC‐sEVs) have shown great application potential in regenerative medicine. To standardise its research and clinical application, the first set of guidelines on hPSC‐sEVs in China ‘Requirements for human pluripotent stem cell derived small extracellular vesicles’ was released by the Chinese Research Hospital Association on 28 December 2021 and came into effect on 1 January 2022. It was jointly drafted and agreed upon by the experts from the Chinese Society of Extracellular Vesicles. This standard specifies the technical requirements, test methods and regulations, packaging, instructions for use, labelling, storage, transportation, and waste handling for hPSC‐sEVs, which apply to the production and quality control of hPSC‐sEVs. We hope that the publication of these guidelines will make it one step closer to international standardisation of hPSC‐sEVs for research and application.

The increasing sodium salts (NaCl, NaHCO3, NaSO4 etc.) in agricultural soil is a serious global concern for sustainable agricultural production and food security. Soybean is an important food crop, and their cultivation is severely challenged by high salt concentration in soils. Classical transgenic and innovative breeding technologies are immediately needed to engineer salt tolerant soybean plants. Additionally, unfolding the molecular switches and the key components of the soybean salt tolerance network are crucial for soybean salt tolerance improvement. Here we review our understandings of the core salt stress response mechanism in soybean. Recent findings described that salt stress sensing, signalling, ionic homeostasis (Na+/K+) and osmotic stress adjustment might be important in regulating the soybean salinity stress response. We also evaluated the importance of antiporters and transporters such as Arabidopsis K+ Transporter 1 (AKT1) potassium channel and the impact of epigenetic modification on soybean salt tolerance. We also review key phytohormones, and osmo-protectants and their role in salt tolerance in soybean. In addition, we discuss the progress of omics technologies for identifying salt stress responsive molecular switches and their targeted engineering for salt tolerance in soybean. This review summarizes recent progress in soybean salt stress functional genomics and way forward for molecular breeding for developing salt-tolerant soybean plant.

BackgroundThe emergence of the new WHO classification standard in 2021 incorporated molecular characteristics into the diagnosis system for meningiomas, making the diagnosis and treatment of meningiomas enter the molecular era.Recent findingsAt present, there are still some problems in the clinical molecular detection of meningioma, such as low attention, excessive detection, and a long cycle. In order to solve these clinical problems, we realized the intraoperative molecular diagnosis of meningioma by combining real-time fluorescence PCR and AIGS, which is also the first known product applied to the intraoperative molecular diagnosis of meningioma.Implications for practiceWe applied AIGS to detect and track a patient with TERTp mutant meningioma, summarized the process of intraoperative molecular diagnosis, and expounded the significance of intraoperative molecular diagnosis under the new classification standard, hoping to optimize the clinical decision-making of meningioma through the diagnosis and treatment plan of this case.

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. However, different PTC variants reveal high heterogeneity at histological, cytological, molecular and clinicopathological levels, which complicates the precise diagnosis and management of PTC. Alternative splicing (AS) has been reported to be potential cancer biomarkers and therapeutic targets.Method: Here, we aim to find a more sophisticated molecular subclassification and characterization for PTC by integrating AS profiling. Based on six differentially expressed alternative splicing (DEAS) events, a new molecular subclassification was proposed to reclassify PTC into three new groups named as Cluster0, Cluster1 and Cluster2 respectively.Results: An in silico prediction was performed for accurate recognition of new groups with the average accuracy of 91.2%. Moreover, series of analyses were implemented to explore the differences of clinicopathology, molecular and immune characteristics across them. It suggests that there are remarkable differences among them, but Cluster2 was characterized by poor prognosis, higher immune heterogeneity and more sensitive to anti-PD1 therapy. The splicing correlation networks proved the complicated regulation relationships between AS events and splicing factors (SFs). An independent prognostic indicator for PTC overall survival (OS) was established. Finally, three compounds (orantinib, tyrphostin-AG-1295 and AG-370) were discovered to be the potential therapeutic agents.Discussion: Overall, the six DEAS events are not only potential biomarkers for precise diagnosis of PTC, but also the probable prognostic predictors. This research would be expected to highlight the effect of AS events on PTC characterization and also provide new insights into refining precise subclassification and improving medical therapy for PTC patients.

Abstract Background The association between gestational diabetes mellitus (GDM) and perinatal depression (PND) remains controversial. Our study aimed to comprehensively assess this association in a longitudinal cohort study with repeated measurements of depression. Methods Our cohort study was nested in a pilot study of an implementation study aiming to screen and manage perinatal depression within the primary health system in China. Women were recruited in the first trimester from May–September 2019 and followed four times up to 1 year postpartum. Data on sociodemographic characteristics and depression were collected using self-developed questionnaires incorporating the Edinburgh Postnatal Depression Scale (EPDS). Oral glucose tolerance test at 24 ~ 28 weeks and fasting plasma glucose (FPG) data were extracted from medical records. Depression throughout the whole period was divided into different trajectories. Associations of GDM with PND at different time periods and PND of different trajectories were determined by logistic regression. The path of association between blood glucose and depression over time was estimated with an autoregressive cross-lagged model. Results In total, 1043 women were included in this analysis and 313 (30.0%) were diagnosed with GDM. The prevalence of depression in the first, second, and third trimesters and postpartum period were 17.2, 6.9, 6.8 and 9.0%, respectively. GDM was neither significantly associated with PND at any time point nor with any specific trajectory of depression. Except for autoregressive paths, no cross-lagged path of FPG and scores of EPDS was significant. Conclusions Our study indicates no association between GDM/blood glucose and PND.

Abstract Objective To study structure-specific solubilization effect of Sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on Remdesivir (RDV) and to understand the experimental clathration with the aid of quantum mechanics (QM), molecular docking and molecular dynamics (MD) calculations. Methods The experiment was carried out by phase solubility method at various pH and temperatures, while the concentration of Remdesivir in the solution was determined by HPLC. The complexation mechanism and the pH dependence of drug loading were investigated following a novel procedure combining QM, MD and molecular docking, based on accurate pKa predictions. Results The phase solubility and solubilization effect of RDV in SBE-β-CD were explored kinetically and thermodynamically for each assessed condition. An optimal drug / SBE-β-CD feeding molar ratio was determined stoichiometrically for RDV solubility in pH1.7 solution. The supersaturated solubility was examined over time after pH of the solution was adjusted from 1.7 to 3.5. A possible hypothesis was raised to elucidate the experimentally observed stabilization of supersaturation based on the proposed RDV Cation A /SBE-β-CD pocket conformations. Conclusion The computational explorations conformed to the experimentally determined phase solubilization and well elucidated the mechanism of macroscopic clathration between RDV and SBE-β-CD from the perspective of microscopic molecular calculations. Graphical Abstract

Water demand prediction is crucial for effective planning and management of water supply systems to handle the problem of water scarcity. Taking into account the uncertainties and imprecisions within the framework of water demand forecasting, the uncertain time series prediction method is introduced for water demand prediction. Uncertain time series is a sequence of imprecisely observed values that are characterized by uncertain variables and the corresponding uncertain autoregressive model (UAR) is employed to describe it for predicting future values. The main contributions of this paper are shown as follows. Firstly, by defining the auto-similarity of uncertain time series, the identification algorithm of UAR model order is proposed. Secondly, a new parameter estimation method based on the uncertain programming is developed. Thirdly, the imprecisely observed values are assumed as the linear uncertain variables and a ratio-based method is presented for constructing the uncertain time series. Finally, the proposed methodologies are applied to model and forecast Beijing's water demand under different confidence levels and compared with the traditional time series, i.e. ARIMA method. The experimental results are evaluated on the basis of performance criteria, which shows that the proposed method outperforms over the ARIMA method for water demand prediction. HIGHLIGHTS Considering the uncertainty of water demand, the uncertain time series method for demand estimation of water resources is presented.; The auto-similarity of uncertain time series is defined, and the identification algorithm of uncertain autoregressive model order is proposed.; An uncertain programming approach to estimate the parameters of model is proposed.; The construction of liner uncertain time series is investigated due to the interval-valued data frequently encountered in real life.;

Abstract Background Colorectal poorly differentiated adenocarcinoma is rarely founded, especially in early-stage. Endoscopic features of early poorly differentiated colorectal cancer in magnifying endoscopy and chromoendoscopy haven’t been clarified. Case presentation A 49-year-old man was referred to our hospital for endoscopic treatment of a lateral spread tumor located in the rectum. We performed pre-resection endoscopic examination for the patient. In magnifying endoscopy with crystal violet staining, the lesion showed irregular microvessels and turned out to be poorly stained with predominantly non-structural pit pattern and a few roundish pits scattered on the surface. The histology revealed a poorly differentiated adenocarcinoma of the rectum invading the deep submucosal layer with negative lymphovascular invasion. Conclusions In this case report, we presented a case of poorly differentiated colorectal adenocarcinoma detected at an early stage, showing interesting endoscopic findings in magnifying endoscopy with crystal violet staining.

Abstract Our previous study demonstrates that a juxtamembrane 2 (JM2) mimic peptide can inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism remains unclear. In this study, JM2 is found to suppress the growth of 4T1 breast tumors by inducing apoptosis and inhibiting the proliferation of 4T1 tumor cells. Further study indicates that JM2 can stimulate the mitochondria to gather near the microtubule-organizing center of tumor cells and subsequently induce ROS-induced ROS release responses, which results in mitochondrial dysfunction and mitochondria-mediated apoptosis. In addition, JM2 can arrest cell cycle in S phase by regulating the expression of cell cycle-related proteins and consequently inhibit proliferation of tumor cells. Then, a previously designed JM2 grafted hyaluronic acid (HA) injectable hydrogel system (HA-JM2) is injected in a breast tumor-resected model and the HA-JM2 hydrogel can inhibit the malignant proliferation of residual tumor cells and suppress the breast tumor recurrence. These findings not only confirm the application potentials of JM2 in anti-tumor therapy and tumor post-surgery treatments but also provide greater understanding on the mechanisms by which JM2 inhibits tumor growth.

Ocean currents, mechanical collisions and electronic damage can cause faults in an autonomous underwater vehicle (AUV), including sensors and thrusters. For such problems, this paper designs a fault-tolerant controller that is independent of the results of the fault diagnosis. An adaptive reaching law is developed based on sliding mode control to shorten convergence times. For the chattering phenomenon, a weighted hyperbolic tangent function is adopted instead of the traditional sign function in sliding mode control. Simulations are carried out when thruster and sensor fail under the condition of ocean current disturbance, model uncertainty and sensor noise. Comparative simulation results show that the proposed method can accelerate the convergence speed of the state point and improve the trajectory tracking effect of the AUV. Consequently, the effectiveness of the proposed method is confirmed.

Transdermal administration of chemo therapeutics into burn healing may be an effective treatment to reduce toxic side effects and improve patient compliance for burns. As a transdermal delivery system, Camelina lipid droplets (CLDs) have received great attention due to their biocompatibility, high drug payload, and rapid absorption. However, the absorbed-related mechanisms of Camelina lipid droplets have not yet been reported. Thus, this paper not only demonstrated that CLD can accelerate skin burn healing through promoting hFGF2 absorption, but also elucidated the mechanism between the skin tissue and keratinocytes using Franz, HE staining, DSC, FTIR spectroscopy, and atomic force microscopy with the presence of CLD-hFGF2 freeze-dried powder. We found that the cumulative release rate of CLD-hFGF2 freeze-dried powder was significantly higher than that of free hFGF2 freeze-dried powder into the skin. At the same time, CLD can change the structure and content of lipids and keratin to increase the permeability of hFGF2 freeze-dried powder in skin tissue. Unlike the free state of hFGF2, the biophysical properties of single cells, including height and adhesion force, were changed under CLD-hFGF2 freeze-dried powder treatment. Meanwhile, CLD-hFGF2 freeze-dried powder was more easily taken up through keratinocytes without damaging cell integrity, which provided a new viewpoint for understanding the absorption mechanism with the CLD system for cellular physiology characteristics. Overall, our findings demonstrated that CLD could break through the stratum corneum (SC) barrier and elucidated the transport mechanism of lipid droplets in skin tissue, which provides a crucial guideline in drug delivery applications for future engineering.

The growing proliferation of geographic information presents a substantial challenge to the traditional framework of a geographic information analysis and service. The dynamic integration and representation of geographic knowledge, such as triples, with spatio-temporal information play a crucial role in constructing a comprehensive spatio-temporal knowledge graph and facilitating the effective utilization of spatio-temporal big data for knowledge-driven service applications. The existing knowledge graph (or geographic knowledge graph) takes spatio-temporal as the attribute of entity, ignoring the role of spatio-temporal information for accurate retrieval of entity objects and adaptive expression of entity objects. This study approaches the correlation between geographic knowledge and spatio-temporal information as a text classification problem, with the aim of addressing the challenge of establishing meaningful connections among spatio-temporal data using advanced deep learning techniques. Specifically, we leverage Wikipedia as a valuable data source for collecting and filtering geographic texts. The Open Information Extraction (OpenIE) tool is employed to extract triples from each sentence, followed by manual annotation of the sentences’ spatio-temporal relevance. This process leads to the formation of quadruples (time relevance/space relevance) or quintuples (spatio-temporal relevance). Subsequently, a comprehensive spatio-temporal classification dataset is constructed for experiment verification. Ten prominent deep learning text classification models are then utilized to conduct experiments covering various aspects of time, space, and spatio-temporal relationships. The experimental results demonstrate that the Bidirectional Encoder Representations from Transformer-Region-based Convolutional Neural Network (BERT-RCNN) model exhibits the highest performance among the evaluated models. Overall, this study establishes a foundation for future knowledge extraction endeavors.

This study aimed to reveal the effects of the hydration products AH3 and AFt phases on the hydration and hardening properties of calcium sulfoaluminate (CSA) cement. In addition, the effects of anhydrite (CS¯) and gypsum (CS¯H2) on the properties of CSA cement were compared. Calcium sulfoaluminate (C4A3S¯) was synthesized with analytical reagents, and the C4A3S¯-CS¯-H2O system with different molar ratios of CS¯ and C4A3S¯ was established. The phase compositions and contents of AFt and AH3 were determined by X-ray diffraction (XRD), Rietveld quantitative phase analysis, and thermogravimetric analysis (TG). The effects of pore structure and hydration product morphology on mechanical properties were analyzed by mercury intrusion porosity (MIP) and scanning electron microscopy (SEM). The results showed that the compressive strength exhibited a correlation with the AH3 content. In the case of relatively sufficient anhydrite or gypsum, C4A3S¯ has a high degree of hydration, and the AH3 content can be considered to contribute more to the strength of the hardened cement paste. When anhydrite was selected, the combined and interlocked AFt crystals were covered or wrapped by a large amount of AH3. The mechanical properties of the hardened cement paste mixed with anhydrite were better than those of that mixed with gypsum.

In this study, the prestressed coating reinforcement method was employed to create kyanite-coated zirconia toughened alumina (ZTA) prestressed ceramics. Due to the mismatch of the coefficient of thermal expansion (CTE) between the coating and substrate, compressive residual stress was introduced in the coating. The effects of compressive residual stress on the mechanical properties of ZTA have been demonstrated. Results show that the flexural strength of the kyanite-coated ZTA ceramics improved by 40% at room temperature compared to ZTA ceramics. In addition, the temperature dependence of mechanical properties has also been discussed. And the results show that the reinforcement gradually diminished with increasing temperature and eventually disappeared at 1000 °C. The modulus of elasticity of the material also exhibits a decreasing trend. Furthermore, the introduction of the prestressing coating enhanced the thermal shock resistance, but the strengthening effect diminished as the temperature increased and completely disappeared at 800 °C.

Abstract This study investigated the exosomal circular RNAs (CircRNAs) produced by tumor-associated macrophages and delivered into the microenvironment of cholangiocarcinoma cells in order to use them as molecular targets for clinical therapy. Tumor-associated M2 macrophages (TAMs) were induced from THP-1 cells and identified by flow cytometry. The TAM-secreted exosomes were isolated from conditioned medium and a CircRNA microarray assay was performed to identify CircRNAs that were uniquely expressed in the isolated exosomes. Circ_0020256 was especially identified based on having the highest differential expression level among all of the CircRNA candidates. In vitro and in vivo experiments were performed to assess the effects of TAMs, exosomes, and Circ_0020256 on the growth and migration of cholangiocarcinoma (CCA) cells. The induced TAMs promoted the proliferation, migration, and invasion of CCA cells and those effects were mediated by exosomes secreted by the TAMs. In CCA cells (RBE and HCCC-9810), Circ_0020256 significantly promoted cellular activity by interacting with its intra-cellular microRNA target, miR-432-5p. In contrast, overexpression of transcription factor E2F3 in CCA cells restored the CCA cellular activities that were inhibited by miR-432-5p. On the other hand, treatment with small interference RNA (siRNA) for Circ_0020256 inhibited CCA cell proliferation, migration, and invasion both in vitro and in vivo. In conclusion, Circ_0020256 in TAM-secreted exosomes promoted the proliferation, migration, and invasion of CCA cells, and that promotional activity was regulated via a Circ_0020256/miR-432-5p/E2F3 axis.

Abstract Effective modification of the structure and properties of halide perovskites via the pressure engineering strategy has attracted enormous interest in the past decade. However, sufficient effort and insights regarding the potential properties and applications of the high‐pressure amorphous phase are still lacking. Here, the superior and tunable photoelectric properties that occur in the pressure‐induced amorphization process of the halide perovskite Cs3Bi2I9 are demonstrated. With increasing pressure, the photocurrent with xenon lamp illumination exhibits a rapid increase and achieves an almost five orders of magnitude increment compared to its initial value. Impressively, a broadband photoresponse from 520 to 1650 nm with an optimal responsivity of 6.81 mA W−1 and fast response times of 95/96 ms at 1650 nm is achieved upon successive compression. The high‐gain, fast, broadband, and dramatically enhanced photoresponse properties of Cs3Bi2I9 are the result of comprehensive photoconductive and photothermoelectric mechanisms, which are associated with enhanced orbital coupling caused by an increase in BiI interactions in the [BiI6]3− cluster, even in the amorphous state. These findings provide new insights for further exploring the potential properties and applications of amorphous perovskites.

SK-2 borehole in Songliao Basin provides unprecedented geological materials for investigating the Early Cretaceous continental paleoenvironment and paleoclimate in northeastern China. The lacustrine successions of the lower Shahezi (K1sh) Formation at the depth from 4,542 to 5,695 m was systematically studied using environmental magnetism and cyclostratigraphy in this study. Magnetic analysis reveals an inverse correlation between magnetic susceptibility (MS) and lithological ranks in fine clastic sediments, with the highest values in mudstones and the lowest in sandstones. The main magnetism carriers in the lower K1sh are pseudo-single-domain (PSD) and/or multi-domain (MD) magnetite with minor presence of hematite. MS was used to further explore the genesis of the environmental and climatic variations through cyclostratigraphic analysis. Sedimentary cycles of 113 m, 34 m, 13 m and 6 m can be identified in the power spectrum, which were interpreted as long and short eccentricity, obliquity, and precession cycles, demonstrating the impact of astronomical cyclicity on sedimentary rhythmicity. Floating astronomical time scale (FATS) of 4,090 kyr and 4,148 kyr were established by tuning the inferred long and short eccentricity cycles to the artificial 405-kyr and 105-kyr orbital eccentricity curves respectively. The estimated sediment accumulation rate around 28 cm/kyr confirms the rapid deposition process within the faulted lacustrine basin. Based on this study, the lake level oscillations in Songliao Basin are assumed to be shaped by long and short eccentricity, precession and semi-precession cycles during Early Cretaceous. This study also indicates that the sand-mudstone alternations deposition in K1sh is most likely driven by the seasonal discrepancies of summer insolation during semi-precession periods.

Abstract “Requirements for human mesenchymal stem cell‐derived small extracellular vesicles” is the first set of guidelines on human mesenchymal stem cell‐derived small extracellular vesicles (hMSC‐sEVs) in China, jointly drafted and agreed upon by experts from the Chinese Society for Extracellular Vesicles. It was released by the Chinese Research Hospital Association on 28 December 2021 and came into effect on 1 January 2022. This standard specifies the technical requirements, test methods and regulations, packaging, instructions for use, labeling, storage, transportation, and waste handling for hMSC‐sEVs, which apply to the production and quality control of hMSC‐sEVs. We hope that the publication of these guidelines will promote consensus on the research and application of human mesenchymal stem cell‐derived small extracellular vesicles and accelerate its international standardization.

This paper concerns a linear porous thermoelastic system, where the heat conduction is given by Cattaneo’s law. By using the theory of the semigroup of the linear operator, the well-posedness is proven. By constructing some suitable multipliers, we establish exponential and polynomial decay rates of the system depending on a stability number π. In addition, we remove the assumption that the constant b is positive in the previous works, which extends some existing results in the literature.

In the field of biological control, there are a large number of systems that gradually evolve over a certain period of time. However, due to some natural or human intervention behavior, the system state will be subjected to some relatively short time interference, so that the system state changes in an instant. This sudden change of state makes the system not simply described by continuous or discrete dynamical systems, but by means of impulse dynamical systems. In this paper, the multi-point boundary value problem of a class of second-order nonlinear impulsive integral differential equations is studied on the basis of impulsive differential equation theory. The main results of this kind of equation are obtained by using the fixed point theorem of strict set contraction operator. Under certain assumptions, the existence of the solution of the equation is proved by constructing the operator on the special cone. Finally, combined with the practical application, the theory was applied to the stability prediction of biological ecosystem, and the correctness of the conclusion was verified.

IntroductionTo determine the clinical effects of laparoscopic surgery (LS) in the treatment of endometriosis and endometriosis-fertility.MethodsTwo hundred twenty-six patients with endometriosis who underwent LS (LS group, n = 176) or laparotomy (LT group, n = 50) at the Third Hospital of Shijiazhuang City from June 2011 to June 2013 were included in this study, and their clinical outcomes for endometriosis and infertility were compared. All patients were followed up for 1 year after surgery to determine postoperative pregnancies in patients with endometriosis.ResultsThe operative times between the LS and LT groups were not significantly different (P > 0.05); however, the length of stay in the hospital and blood loss in the LS group were significantly different from the LT group (P

Soybean (Glycine max L.) is susceptible to low temperatures. Increasing lines of evidence indicate that abiotic stress-responsive genes are involved in plant low-temperature stress response. However, the involvement of photosynthesis, antioxidants and metabolites genes in low temperature response is largely unexplored in Soybean. In the current study, a genetic panel of diverse soybean varieties was analyzed for photosynthesis, chlorophyll fluorescence and leaf injury parameters under cold stress and control conditions. This helps us to identify cold tolerant (V100) and cold sensitive (V45) varieties. The V100 variety outperformed for antioxidant enzymes activities and relative expression of photosynthesis (Glyma.08G204800.1, Glyma.12G232000.1), GmSOD (GmSOD01, GmSOD08), GmPOD (GmPOD29, GmPOD47), trehalose (GmTPS01, GmTPS13) and cold marker genes (DREB1E, DREB1D, SCOF1) than V45 under cold stress. Upon cold stress, the V100 variety showed reduced accumulation of H2O2 and MDA levels and subsequently showed lower leaf injury compared to V45. Together, our results uncovered new avenues for identifying cold tolerant soybean varieties from a large panel. Additionally, we identified the role of antioxidants, osmo-protectants and their posttranscriptional regulators miRNAs such as miR319, miR394, miR397, and miR398 in Soybean cold stress tolerance.

Soybean [Glycine max (L.) Merr.] provides a rich source of plant protein and oil worldwide. The commercial use of transgenic technology in soybean has become a classical example of the application of biotechnology to crop improvement. Although genetically modified soybeans have achieved commercial success, hybrid soybean breeding is also a potential way to increase soybean yield. Soybean cytoplasmic male-sterile (CMS) lines have been used in three-line hybrid breeding systems, but their application to exploiting soybean heterosis has been limited by rare germplasm resource of sterile lines. The generation of various genetic diversity male-sterile soybean lines will help to overcome the shortcoming. In this study, we used targeted editing of AMS homologs in soybean by CRISPR/Cas9 technology for the first time to generate stable male-sterile lines. Targeted editing of GmAMS1 resulted in a male-sterile phenotype, while editing of GmAMS2 failed to produce male-sterile lines. GmAMS1 functions not only in the formation of the pollen wall but also in the controlling the degradation of the soybean tapetum. CRISPR/Cas9 technology could be used to rapidly produce stable male-sterile lines, providing new sterile-line materials for soybean hybrid breeding systems.

Abstract Numerous studies have confirmed the great application potentials of small extracellular vesicles (sEVs) in biological medical field, especially in tissue repair and regeneration. However, the production capability of sEVs by noncancerous cells is very limited, while their dosage requirements in disease treatments are usually very high. Meanwhile, as cell aging, the sEV production capability of cells decreases and the biological function of sEVs changes accordingly. In addition, for special applications, sEVs carrying desired bioactive substances should be designed to perform their expected biological function. Therefore, improving the production of sEVs and precisely regulating their biological function are of great significance for promoting the clinical applications of sEVs. In this review, some of the current classic strategies in affecting the cellular behaviors of donor cells and subsequently regulating the production and biological function of their sEVs are summarized, including gene engineering methods, stress-inducing conditions, chemical regulators, physical methods, and biomaterial stimulations. Through applying these strategies, increased yield of sEVs with required biological function can be obtained for disease treatment and tissue repair, such as bone regeneration, wound healing, nerve function recovery and cancer treatment, which could not only reduce the harvest cost of sEV but promote the practical applications of sEVs in clinic. Graphical Abstract