Search

Abstract Traditionally, lactate has been considered a ‘waste product’ of cellular metabolism. Recent findings have shown that lactate is a substance that plays an indispensable role in various physiological cellular functions and contributes to energy metabolism and signal transduction during immune and inflammatory responses. The discovery of lactylation further revealed the role of lactate in regulating inflammatory processes. In this review, we comprehensively summarize the paradoxical characteristics of lactate metabolism in the inflammatory microenvironment and highlight the pivotal roles of lactate homeostasis, the lactate shuttle, and lactylation (‘lactate clock’) in acute and chronic inflammatory responses from a molecular perspective. We especially focused on lactate and lactate receptors with either proinflammatory or anti-inflammatory effects on complex molecular biological signalling pathways and investigated the dynamic changes in inflammatory immune cells in the lactate-related inflammatory microenvironment. Moreover, we reviewed progress on the use of lactate as a therapeutic target for regulating the inflammatory response, which may provide a new perspective for treating inflammation-related diseases.

Abstract Activatable afterglow luminescence nanoprobes enabling switched “off-on” signals in response to biomarkers have recently emerged to achieve reduced unspecific signals and improved imaging fidelity. However, such nanoprobes always use a biomarker-interrupted energy transfer to obtain an activatable signal, which necessitates a strict distance requisition between a donor and an acceptor moiety (

ABSTRACTIn this study, mice undergoing either short maternal separation (MS) or long MS during early postnatal life and then experiencing chronic unpredictable mild stress (CUMS) in adulthood were established to explore the critical mechanism of the ginseng total saponins (GTS), extractions of ginseng, on early-life stress (ELS) and subsequent susceptibility to depression-like behaviors in adulthood. The behavioral assessment confirmed that GTS could reduce susceptible effects on mice induced by ELS to develop subsequent adult depression-like behaviors. The epigenetic changes of brain-derived neurotrophic factor (BDNF), its receptor tropomyosin-related kinase B (TrkB), and the downstream target cAMP-response element-binding protein (CREB) in the hippocampal tissue were elevated after GTS treatment. Interestingly, the inhibitor of TrKB, K252a further verified the above findings. All evidence showed that GTS had potential neuroprotective effects due to GTS could restore behavioral abnormalities and alter hippocampal protein levels via the CREB-BDNF-TrkB pathway, thereby ameliorating depression-like behaviors induced by MS.

Higher education faculty's autonomous support of online teaching can promote students engagement in online context. This study collected 492 Chinese university students' survey questionnaires and applied structural equation model to measure their teacher autonomy support, self-efficacy, self-regulated learning (SRL), and online learning engagement. This study adopted self-determination theory (SDT), systematically explored the relationship between teachers' autonomy support and student learning engagement from the perspective of online contexts, and examined the mediating effects of students' self-efficacy and self-regulated learning (SRL) in online contexts. This study found that teacher autonomy support had a significant effect on student engagement in online learning, and was mediated by self-efficacy. Teacher-directed support had a significant effect on student engagement in online learning mediated by SRL. Teacher-directed support had a significant impact on online learning with self-efficacy and SRL as the main mediating variables. Therefore, this study gave a fresh perspective to improve students' online learning engagement, that is to say, teachers were encourage to improve students' autonomy in practical teaching on the basis of giving students autonomy support. Students can promote online learning engagement by strengthening self-efficacy and self-regulation through organizational exchanges and mutual assistance and cooperation of students.

Higher education faculty’s autonomous support of online teaching can promote students engagement in online context. This study collected 492 Chinese university students’ survey questionnaires and applied structural equation model to measure their teacher autonomy support, self-efficacy, self-regulated learning (SRL), and online learning engagement. This study adopted self-determination theory (SDT), systematically explored the relationship between teachers’ autonomy support and student learning engagement from the perspective of online contexts, and examined the mediating effects of students’ self-efficacy and self-regulated learning (SRL) in online contexts. This study found that teacher autonomy support had a significant effect on student engagement in online learning, and was mediated by self-efficacy. Teacher-directed support had a significant effect on student engagement in online learning mediated by SRL. Teacher-directed support had a significant impact on online learning with self-efficacy and SRL as the main mediating variables. Therefore, this study gave a fresh perspective to improve students’ online learning engagement, that is to say, teachers were encourage to improve students’ autonomy in practical teaching on the basis of giving students autonomy support. Students can promote online learning engagement by strengthening self-efficacy and self-regulation through organizational exchanges and mutual assistance and cooperation of students.

Abstract Precise detection of early osteolytic metastases is crucial for their treatment but remains challenging in the clinic because of the limited sensitivity and specificity of traditional imaging techniques. Although fluorescence imaging offers attractive features for the diagnosis of osteolytic metastases, it is hampered by limited penetration depth. To address this issue, a fluoro‐photoacoustic dual‐modality imaging probe comprising a near‐infrared dye caged by a cathepsin K (CTSK)‐cleavable peptide sequence on one side and functionalized with osteophilic alendronate through a polyethylene glycol linker on the other side is reported. Through systematic in vitro and in vivo experiments, it is demonstrated that in response to CTSK, the probe generated both near‐infrared fluorescent and photoacoustic signals from bone metastatic regions, thus offering a potential strategy for detecting deep‐seated early osteolytic metastases.

Few studies have focused on the link between active surveillance (AS) and Gleason score upgrade (GSU) and its impact on the prognosis of patients with prostate cancer (PCa). This study aimed to analyze the effect of AS duration on GSU and prognostic value based on risk stratification. All eligible patients were risk-stratified according to AUA guidelines into low-risk (LR), favorable intermediate-risk (FIR), and unfavorable intermediate-risk (UIR) PCa. Within the Surveillance, Epidemiology, and End Results Program (SEER) database, 28,368 LR, 27,243 FIR, and 12,210 UIR PCa patients were included. The relationship between AS duration and GSU was identified with univariate and multivariate logistic regression. Discrimination according to risk stratification of AS duration and GSU was tested by Kaplan–Meier analysis and competing risk regression models. The proportion of patients who chose AS was the highest among LR PCa (3434, 12.1%), while the proportion in UIR PCa was the lowest (887, 7.3%). The AS duration was only associated with GSU in LR PCa, with a high Gleason score (GS) at diagnosis being a strong predictor of GSU for FIR and UIR PCa. Kaplan–Meier analysis indicated that long-term surveillance only made a significant difference in prognosis in UIR PCa. The competing risk analysis indicated that once GS was upgraded to 8 or above, the prognosis in each group was significantly worse. AS is recommended for LR and FIR PCa until GS is upgraded to 8, but AS may not be suitable for some UIR PCa patients.

Written corrective feedback in Second Language Writing is one of the most important parts in L2 Acquisition and Language Teaching. CiteSpace is a convenient and effective bibliometric analysis tool which is widely used by researchers to explore the development tends of a certain field. The Web of Science core collection database was used as the primary source for data collection. There were 272 effective articles were selected from 2001 to 2021. The hot research topics in recent 20 years and emerging trends were showed. It was found that the research of written corrective feedback has entered a period of rapid development after the accumulation of basic knowledge in the early stage. Many empirical studies have been carried out. The distribution, cooperation, development trends and hotpots of current research are presented through visual map analysis in this study. In the future, the written corrective feedback research could try to concentrate on the psychological process and feedback providers, and it is also suggested to combine interdisciplinary knowledge such as education, psychology, neurology, etc., and use new research and measurement methods to promote the development of written corrective feedback.

Abstract Dorzagliatin is a novel allosteric glucokinase activator targeting both pancreatic and hepatic glucokinase currently under clinical investigation for treatment of type 2 diabetes (T2D). This study aimed to investigate the effect of renal impairment (RI) on dorzagliatin’s pharmacokinetics (PKs) and safety, and to guide appropriate clinical dosing in patients with diabetic kidney disease, including end‐stage renal disease (ESRD). Based on the results from physiologically‐based pharmacokinetic modeling, the predicted outcome of RI on dorzagliatin PK property would be minimum that the plasma exposure area under concentration (AUC) of dorzagliatin in patients with ESRD would increase at about 30% with minimal change in peak concentration (Cmax) comparing to those in healthy volunteers (HVs). To definitively confirm the prediction, a two‐part RI study was designed and conducted based on regulatory guidance starting with the patients with ESRD matched with HVs. Results of the RI study showed minimum difference between patients with ESRD and HVs with respect to dorzagliatin exposure with geometric mean ratio of ESRD to HV at 0.81 for Cmax and 1.11 for AUC. The elimination half‐life, volume of distribution, and systemic clearance for dorzagliatin were similar between the two groups. Dorzagliatin was well‐tolerated in patients with ESRD during the study. Therefore, RI showed no significant impact on dorzagliatin PK, suggesting that dorzagliatin can be readily used in patients with T2D at all stages of RI without need for dose adjustment.

It is generally recognized that the quality differences in plant germplasm resources are genetically determined, and that only a good "pedigree" can have good quality. Ecological memory of plants and rhizosphere soil fungi provides a new perspective to understand this phenomenon. Here, we selected 45 tea tree germplasm resources and analyzed the rhizosphere soil fungi, nutrient content and tea quality. We found that the ecological memory of tea trees for soil fungi led to the recruitment and aggregation of dominant fungal populations that were similar across tea tree varieties, differing only in the number of fungi. We performed continuous simulation and validation to identify four characteristic fungal genera that determined the quality differences. Further analysis showed that the greater the recruitment and aggregation of Saitozyma and Archaeorhizomyces by tea trees, the greater the rejection of Chaetomium and Trechispora, the higher the available nutrient content in the soil and the better the tea quality. In summary, our study presents a new perspective, showing that ecological memory between tea trees and rhizosphere soil fungi leads to differences in plants' ability to recruit and aggregate characteristic fungi, which is one of the most important determinants of tea quality. The artificial inoculation of rhizosphere fungi may reconstruct the ecological memory of tea trees and substantially improve their quality. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of lycorine hydrochloride (LH) on the proliferation, migration and invasion of human gastric cancer cell line MGC-803 and its possible mechanism. Methods Cell proliferation ability was detected by MTT assay and colony formation assay. Distribution of cell cycle was detected by flow cytometry. The migration ability of cells was detected by wound healing assay. Transwell assay was used to detect the invasion ability of cells. RT-qPCR was used to detect the effects of LH on gene expression of cell migration and invasion. Results The inhibitory rate of LH on MGC-803 cells was concentration and time dependent (P＜0.05, P＜0.01), and the IC50 value at 48 h was 3.76 μmol/L. The colony formation of MGC-803 cells was significantly inhibited by LH, and the colony formation was completely inhibited when the concentration reached 20 μmol/L (P＜0.01). Cell cycle was arrested in S phase after LH treatment (P＜0.01). With the increase of LH concentration, cell migration and invasion were significantly inhibited (P＜0.01), the expression level of miR-203 gene was up-regulated, while the expression levels of Slug, MMP2 and MMP9 were down-regulated in a concentration-dependent manner (P＜0.05, P＜0.01). Conclusions LH significantly inhibited the proliferation of MGC-803 cells, induced cell cycle arresting in the S phase, and inhibited cell migration and invasion. The expression level of miR-203 gene was up-regulated.

The purpose of this study was to investigate the predictors of metastatic patterns of upper tract urothelial carcinoma (UTUC) and to analyze the surgical outcomes of different metastatic patterns of UTUC. Data on patients with UTUC from 2010 to 2017 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan–Meier analysis was applied to compare the patients' survival distributions. Univariate and multivariate logistic regression was used to assess the specific predictors of site-specific metastases, while competitive risk regression was applied to estimate the predictors of cancer-specific mortality in patients with metastases. A total of 9,436 patients were enrolled from the SEER database, of which 1,255 patients had distant metastases. Lung metastasis (42.5%) was most common and patients with single distant lymph node metastasis had a better prognosis. Clinical N stage (N1, N2, N3) was the strongest predictors of the site specific metastatic sites. Renal pelvis carcinoma was more prone to develop lung metastases (OR = 1.67, P

The three-dimensional carbon fiber fabric was densified by chemical vapor infiltration and precursor impregnation cracking composite process, and the high thermal conductivity 3D C/C composite material with density of 1.95 g/cm3 was obtained. Using SEM, XRD, thermal conductivity test, linear expansion coefficient test and three-point bending experiment to study the effect of different heat treatment temperatures of 2350,2550,2850℃ on the microscopic morphology,structure, thermal conductivity, linear expansion coefficient and bending performance of 3D C/C composites. The results show that with the increase of the heat treatment temperature, the mesophase pitch-based carbon fiber graphite sheet structure becomes more obvious, the order of the pyrolytic carbon sheets evenly wrapped around the carbon fiber increases, and the arrangement between the sheets becomes more dense; the graphitization and thermal conductivity of 3D C/C composite materials improve; in the test temperature range of 250-1400℃, the linear expansion coefficient increases slightly with the increase of the test temperature, and the 3D C/C composite after different heat treatment temperatures. The linear expansion coefficient of the materials is -1×10-6-2×10-6℃-1, showing good "zero expansion". In addition, when the heat treatment temperature increases, the bonding of the carbon fiber and the matrix of the 3D C/C composite materials are weakened, resulting in the decrease in the bending strength and flexural modulus of the materials. A large number of long fibers are pulled out on the bending fracture surface of the materials after the high temperature heat treatment at 2850℃. In general, the fracture after three different heat treatment temperatures shows "pseudoplastic" fracture characteristics.

Abstract Existing data on the prognosis and clinicopathological features of patients with metastatic renal cell carcinoma (mRCC) are limited. This study aims to investigate the prognostic value and clinicopathological features of different metastatic sites in patients with mRCC. A dataset from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database consisting of 18 registries (1973–2015) was selected for a retrospective mRCC cohort study. Information was included on the metastatic sites in lung, bone, liver, and brain. Kaplan–Meier analysis was applied to compare the survival distribution. Univariate and multivariate Cox regression models were used to analyze survival outcomes. From the SEER database, a total of 10,410 patients with primary mRCC from 2010 to 2015 were enrolled in this cohort study. Analysis indicated that 54.9%, 37.7%, 19.5%, and 10.4% of patients were found to have lung, bone, liver, and brain metastasis, respectively. There was a significantly higher risk for sarcomatoid RCC patients to develop liver metastasis as compared to patients with clear cell RCC. The median survival for patients with lung, bone, liver, or brain metastasis was 7 months, 7 months, 4 months, and 5 months, respectively. Various clinicopathological features and prognostic values are associated with different metastatic sites. Understanding these differences may enable targeted pre-treatment assessment of primary mRCC and personalized curative intervention for patients.

Online learning have played a very significant role for achieving professional and academic qualifications in higher education. There have been more and more researches that explore the issues of learning activities, satisfaction, engagement, and interactions between instructors and students. To promote learning engagement in online learning environments in higher education, this study collected data from 334 full-time undergraduate students in a large public Chinese university and explored the correlation of online interaction, self-regulation learning and social presence on learning engagement in online environments. The research findings indicated that online interaction affected social presence and indirectly affected learning engagement through social presence. In addition, social presence affected learning engagement, self-regulation affected social presence, and social presence also mediated the relationship between self-regulation and learning engagement. This study reported that self-regulation learning and social presence had positive correlation with on students’ learning engagement in online environments. The findings of this study have significant practical implications for teaching practices.

Hepatocellular carcinoma (HCC) is typically fatal, and patients with hepatocellular carcinoma are usually diagnosed at the late stages. Although the treatments for HCC have been rapidly advancing, novel targets for HCC are still desperately needed, especially for targeted therapies. Here, we identified an enriched long non-coding RNA, AC006262.5, associated with HCC, that promoted the proliferation, migration, and invasiveness of HCC cells, both in vitro and in vivo. In addition, our results revealed that AC006262.5 bound to and regulated miR-7855-5p, a tumor-suppressive miRNA, in HCC. Moreover, our data show that AC006262.5 regulates the expression of BPY2C via miR-7855-5p. Finally, we found that AC006262.5 and miR-7855-5p formed a regulatory loop. Upregulation of AC006262.5 resulted in decreased expression of miR-7855-5p, and downregulation of miR-7855-5p further facilitated the expression of AC006262.5. Our work provides novel targets for HCC diagnosis and treatment, and sheds light on the lncRNA-miRNA regulatory nexus that controls the pathology of HCC. Key words: HCC, LncRNA, AC006262.5, miR-7855-5p, BPY2C. Le carcinome hépatocellulaire (CHC) constitue une menace énorme pour l'humain et les patients atteints de carcinome hépatocellulaire sont généralement diagnostiqués à des stades tardifs. Bien que le traitement du CHC ait récemment progressé rapidement, de nouvelles cibles en lien avec le CHC sont toujours désespérément nécessaires, en particulier en médecine de précision. Les auteurs ont identifié ici un ARN long non codant enrichi dans le CHC, l'AC006262.5, qui favorise la prolifération, la migration et l'invasion du CHC in vitro et in vivo. En outre, leurs résultats ont révélé que l'AC006262.5 se liait au miR-7855-5p, un miARN suppresseur de tumeur dans le CHC, et le régulait. De plus, leurs données ont montré que l'AC006262.5 régulait l'expression de BPY2C par l'intermédiaire du miR-7855-5p. Enfin, ils ont constaté que l'AC006262.5 et le miR-7855-5p formaient une boucle de régulation. La régulation à la hausse de l'AC006262.5 entraînait une diminution de l'expression du miR-7855-5p et la régulation à la baisse du miR-7855-5p facilitait l'expression de l'AC006262.5. Ces travaux ont fourni de nouvelles cibles pour le diagnostic et le traitement du CHC et ont mis en lumière le lien de régulation entre l'ARNlnc et le miRNA qui contrôle la pathologie du CHC. [Traduit par la Rédaction] Mots-clés: CHC, ARNlnc, AC006262.5, miR-7855-5p, BPY2C., Introduction Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide (D. Li et al. 2018). Even with the rapid accumulation of studies illustrating the mechanisms behind [...]

Context Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. Objective To observe the clinical safety and tolerability of CALAS. Materials and methods Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. Results Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). Discussion and conclusions CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.

There are obvious differences in quality between different varieties of the same plant, and it is not clear whether they can be effectively distinguished from each other from a bacterial point of view. In this study, 44 tea tree varieties (Camellia sinensis) were used to analyze the rhizosphere soil bacterial community using high-throughput sequencing technology, and five types of machine deep learning were used for modeling to obtain characteristic microorganisms that can effectively differentiate different varieties, and validation was performed. The relationship between characteristic microorganisms, soil nutrient transformation, and tea quality formation was further analyzed. It was found that 44 tea tree varieties were classified into two groups (group A and group B) and the characteristic bacteria that distinguished them came from 23 genera. Secondly, the content of rhizosphere soil available nutrients (available nitrogen, available phosphorus, and available potassium) and tea quality indexes (tea polyphenols, theanine, and caffeine) was significantly higher in group A than in group B. The classification result based on both was consistent with the above bacteria. This study provides a new insight and research methodology into the main reasons for the formation of quality differences among different varieties of the same plant. [ABSTRACT FROM AUTHOR]

Tea plant is an acidophilic plant, and soil pH has an important effect on the absorption and enrichment of elements, tea plant growth and quality. In this study, rhizosphere soils and leaves of tea plants from 30 tea plantations were collected to determine soil pH and multi-element content of soil and leaves of tea plants, to obtain and validate key elements that are enriched by pH affecting tea plants, and to analyze the effects of pH on the growth and quality of tea plants. The results showed that soil pH significantly affected the enrichment of 15 elements by tea plants, and the enrichment coefficients of 11 elements (C, Mg, Si, N, P, Mn, Sr, Cd, S, Ca and Sb) tended to increase significantly with the increase of soil pH, while the opposite was true for the other four elements (Cu, Rb, Ba and Al). TOPSIS analysis showed that soil pH had the greatest effect on tea plant enrichment of seven elements, namely N (100%), Mn (43.32%), C (39.22%), P (27.66%), Sr (15.30%), Mg (13.41%) and Ba (10.47%). Pot experiments with tea seedlings also verified that soil pH significantly affected the enrichment of tea leaves for seven key elements. Moreover, with the increase of soil pH, the growth indexes, photosynthesis indexes and quality indexes of tea seedlings showed a significant upward trend. Interaction analysis showed that the enhanced enrichment of N, Mn, C, P, Sr and Mg by tea plants was beneficial to increase the photosynthetic capacity of tea plants, promote the growth of tea plants and improve the quality of tea leaves. This study provides an important theoretical basis for the cultivation and management of tea plants. [ABSTRACT FROM AUTHOR]

Aviation mutagenesis is a breeding method for the rapid selection of superior plant varieties. In this study, rhizosphere soil chemical indexes, soil enzyme activities, and soil metabolites were measured in Dahongpao tea trees with aviation mutagenesis (TM) and without aviation mutagenesis (CK). The main soil metabolites distinguishing TM and CK and their relationships with soil chemical indexes and soil enzyme activities were analyzed and obtained. The results showed that there was no significant change in the rhizosphere soils' pH of TM tea trees compared to CK (p = 0.91), while all other chemical indexes of TM were significantly higher than CK (p < 0.05). In addition, the activities of enzymes related to soil nutrient cycling such as urease, protease, sucrase, acid phosphatase and cellulase, and enzymes related to soil antioxidants such as superoxide dismutase, catalase, peroxidase, and polyphenol oxidase were significantly increased (p < 0.05) in the rhizosphere soils of TM tea trees compared to CK. Soil metabolite analysis showed that the main soil metabolites distinguishing CK from TM were carbohydrates, nitrogen compounds, and amines. Of these, carbohydrates and nitrogen compounds were significantly positively correlated with soil chemical indexes and soil enzymes, whereas amine was significantly negatively correlated with soil chemical indexes such as organic matter, total nitrogen, total potassium, available nitrogen, available phosphorus; amine showed significant negative correlation with soil enzymes such as catalase, peroxidase, polyphenol oxidase, and urease. It can be seen that aviation mutagenesis is conducive to improving the ability of tea tree rhizosphere aggregation and transformation of soil nutrients, increasing the total amount of soil nutrients and the content of available nutrients, which is more conducive to promoting the uptake of nutrients by the tea tree, and thus promoting the growth of the tea tree. [ABSTRACT FROM AUTHOR]

The quality of the Dahongpao mother tree (Camellia sinensis) remains a mystery to this day. In this study, for the first time, the differences between the Dahongpao mother tree (MD) and Dahongpao cuttings (PD), in terms of odor characteristics and taste characteristics were analyzed by metabomics. The results showed that MD had stronger floral, fruity, green, and woody odor characteristics than PD, and that the contributions were mainly from dihydromyrcenol, methyl salicylate, 2-isobutylpyrazine, 1,6-dihydrocarveol, gamma-terpineol, and linalyl acetate. Further, fresh and brisk taste and mellowness taste characteristics of MD were significantly higher than PD, with contributions mainly from amino acids and derivatives and organic acids. Secondly, bitterness taste characteristics of PD were significantly higher than MD, with contributions from phenolic acids, flavones, and flavonols. This study preliminarily unraveled the legend of the superior quality of the Dahongpao mother tree, and also provided an important reference for the breeding of tea-tree cuttings. [ABSTRACT FROM AUTHOR]