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The structural characteristics, acetylcholinesterase inhibitory activity, and immune effects of two purified acid polysaccharides from Chrysanthemum morifolium cv. Gongju were investigated. GJP-1 and GJP-2 were isolated and purified using DEAE-sepharose and Sephadex G-100 chromatography. GJP-1 consisted of Man, Rha, Ara, Glc, Gal, and GalA, with a ratio of 1.99:3.98:81.2:2.65:7.03:3.15, while GJP-2 comprised of Man, Rha, Ara, Glc, Gal, and GalA in a ratio of 0.27:2.36:8.03:38.44:2.38:48.52. GJP-2 is a kind of pectin-type polysaccharide. GJP-1 and GJP-2 differed in average molecular weight of 5.86 kDa and 4.92 kDa. The results indicated that GJP-1 and GJP-2 significantly inhibited the activity of acetylcholinesterase and had good immunomodulatory activities. GJP-1 and GJP-2 are bioactive polysaccharides with the potential to improve cognitive function. GJP-2 promoted more proliferation, as well as the release of tumor necrosis factor-α and interferon γ. Clarifying the structures and bioactivities of polysaccharides could lay a foundation for the application of Gongju in functional foods and medicines production., Competing Interests: Declaration of competing interest The authors confirm that they have no conflicts of interest with respect to the study described in this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Accurate segmentation of the left atrium (LA) from late gadolinium-enhanced cardiac magnetic resonance (LGE CMR) images is crucial for aiding the treatment of patients with atrial fibrillation. Few-shot learning holds significant potential for achieving accurate LA segmentation with low demand on high-cost labeled LGE CMR data and fast generalization across different centers. However, accurate LA segmentation with few-shot learning is a challenging task due to the low-intensity contrast between the LA and other neighboring organs in LGE CMR images. To address this issue, we propose an Adaptive Dynamic Inference Network (ADINet) that explicitly models the differences between the foreground and background. Specifically, ADINet leverages dynamic collaborative inference (DCI) and dynamic reverse inference (DRI) to adaptively allocate semantic-aware and spatial-specific convolution weights and indication information. These allocations are conditioned on the support foreground and background knowledge, utilizing pixel-wise correlations, for different spatial positions of query images. The convolution weights adapt to different visual patterns based on spatial positions, enabling effective encoding of differences between foreground and background regions. Meanwhile, the indication information adapts to the background visual pattern to reversely decode foreground LA regions, leveraging their spatial complementarity. To promote the learning of ADINet, we propose hierarchical supervision, which enforces spatial consistency and differences between the background and foreground regions through pixel-wise semantic supervision and pixel-pixel correlation supervision. We demonstrated the performance of ADINet on three LGE CMR datasets from different centers. Compared to state-of-the-art methods with ten available samples, ADINet yielded better segmentation performance in terms of four metrics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Available evidence suggests that air pollutants can cause stroke, but little research has investigated the confounding effects of urban-rural differences. Here, we investigated the urban-rural difference in the correlation between particulate matter (PM 2.5 and PM 10 ) exposure and stroke. This cohort study was based on a prospective multi-city community-based cohort (Guizhou Population Health Cohort Study (GPHCS)) in Guizhou Province, China. A total of 7988 eligible individuals (≥18 years) were enrolled with baseline assessments from November 2010 to December 2012, and follow-up was completed by June 2020. Two major particulate matters (PMs, including PM 2.5 and PM 10 ) were assessed monthly from 2000 by using satellite-based spatiotemporal models. The risk of stroke was estimated using a Cox proportional hazard regression model. The association between particulate matters' exposure and stroke in different areas (total, urban, and rural) and the potential modification effect of comorbidities (hypertension, diabetes, and dyslipidemia) and age (≤65/>65 years) were examined using stratified analyses. The risk of stroke increased for every 10 μg/m 3 increase in mean PMs' concentrations during the previous 1 year at the residential address (HR: 1.26, 95%CI: 1.24, 1.29 (PM 2.5 ); HR: 1.13, 95%CI: 1.11, 1.15 (PM 10 )). The presence of diabetes and dyslipidemia increased the risk of PM 10 -induced stroke in whole, urban, and rural areas. Specifically, people living in rural areas were more likely to experience the effects of PMs in causing a stroke. The risk of stroke due to PMs was statistically increased in the young and older populations living in rural areas. In conclusion, long-term exposure to PMs increased the risk of stroke and such association was more pronounced in people living in rural areas with lower income levels. Diabetes and dyslipidemia seemed to strengthen the association between PMs and stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria, while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The advent of online education has become indispensable for nursing students seeking to acquire knowledge. However, the efficacy of online education often falls short of initial expectations. Deep learning (DL) can assist learners tackle complex problems and make innovative decisions. Despite its potential, there has been limited exploration into the underlying mechanisms of DL among nursing students, both domestically and globally. This study examined the potential moderating effect of psychological capital (PC) on the association between academic self-concept (AS-c) and DL among nursing students from China enrolled in online courses. Conducted from October 2022 to January 2023, the survey involved 635 nursing students from four public universities in eastern China, utilizing convenience sampling. Data was collected using the AS-c scale, psychological capital scale, and DL scale in online courses. Correlation analyses, univariate analyses, multiple linear regression analyses, and the PROCESS macro were employed for a comprehensive examination. The results revealed a strong positive relationship between nursing students' DL and both their AS-c (r = 0.766, P  < 0.01) and PC (r = 0.714, P  < 0.01), respectively. Additionally, the effect of AS-c on DL was stronger among individuals with high PC (β = 0.34, SE = 0.03, P  < 0.001) compared to those with low (β = 0.29, SE = 0.02, P  < 0.001) or medium (β = 0.24, SE = 0.02, P  < 0.001) levels of PC, indicating that PC exerts moderating effects and promotes DL among nursing students enrolled in online courses. Based on these findings, several implications are suggested for the theory and practice of facilitating DL., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Siai Zhang reports financial support was provided by Tianjin Education Bureau. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Ovarian cancer is a malignant tumor that seriously endangers health. Early ovarian cancer symptoms are frequently challenging to detect, resulting in a large proportion of patients reaching an advanced stage when diagnosed. Conventional diagnosis relies heavily on serum biomarkers and pathological examination, but their sensitivity and specificity require improvement. Targeted therapy inhibits tumor growth by targeting certain characteristics of tumor cells, such as signaling pathways and gene mutations. However, the effectiveness of targeted therapy varies among individuals due to differences in their unique biological characteristics and requires individualized strategies. Immunotherapy is a promising treatment for ovarian cancer due to its long-lasting antitumor effect. Nevertheless, issues such as variable efficacy, immune-associated adverse effects and drug resistance remain to be resolved. The present review discusses the diagnostic strategies, rationale, treatment strategies and prospects of targeted therapy and immunotherapy for ovarian cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Li et al.)

Purpose: To develop and validate an end-to-end model for automatically predicting hematoma expansion (HE) after spontaneous intracerebral hemorrhage (sICH) using a novel deep learning framework., Methods: This multicenter retrospective study collected cranial noncontrast computed tomography (NCCT) images of 490 patients with sICH at admission for model training (n = 236), internal testing (n = 60), and external testing (n = 194). A HE-Mind model was designed to predict HE, which consists of a densely connected U-net for segmentation process, a multi-instance learning strategy for resolving label ambiguity and a Siamese network for classification process. Two radiomics models based on support vector machine or logistic regression and two deep learning models based on residual network or Swin transformer were developed for performance comparison. Reader experiments including physician diagnosis mode and artificial intelligence mode were conducted for efficiency comparison., Results: The HE-Mind model showed better performance compared to the comparative models in predicting HE, with areas under the curve of 0.849 and 0.809 in the internal and external test sets respectively. With the assistance of the HE-Mind model, the predictive accuracy and work efficiency of the emergency physician, junior radiologist, and senior radiologist were significantly improved, with accuracies of 0.768, 0.789, and 0.809 respectively, and reporting times of 7.26 s, 5.08 s, and 3.99 s respectively., Conclusions: The HE-Mind model could rapidly and automatically process the NCCT data and predict HE after sICH within three seconds, indicating its potential to assist physicians in the clinical diagnosis workflow of HE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

MicroRNAs (miRNAs) reportedly play significant roles in the progression of various cancers and hold huge potential as both diagnostic tools and therapeutic targets. Given the ongoing uncertainty surrounding the precise functions of several miRNAs in cholangiocarcinoma (CCA), this research undertakes a comprehensive analysis of CCA data sourced from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The present study identified a novel miRNA, specifically miR-26b-3p, which exhibited prognostic value for individuals with CCA. Notably, miR-26b-3p was upregulated within CCA samples, with an inverse correlation established with patient prognosis (Hazard Ratio = 8.19, p = 0.018). Through a combination of functional enrichment analysis, analysis of the LncRNA-miR-26b-3p-mRNA interaction network, and validation by qRT PCR and western blotting, this study uncovered the potential of miR-26b-3p in potentiating the malignant progression of CCA via regulation of essential genes (including PSMD14, XAB2, SLC4A4) implicated in processes such as endoplasmic reticulum (ER) stress and responses to misfolded proteins. Our findings introduce novel and valuable insights that position miR-26b-3p-associated genes as promising biomarkers for the diagnosis and treatment of CCA., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with limited treatment options and poor prognosis. In this study, we reveal the pivotal role of Stratifin (SFN), also recognized as 14-3-3σ, in driving HCC progression. Our investigation underscores a substantial upregulation of SFN within HCC tissues, manifesting a significant association with worse prognostic outcomes among HCC patients. In vitro and in vivo experiments reveal that SFN overexpression significantly amplifies proliferation, mitigates sorafenib-induced effects on HCC cells, and enhances tumorigenesis. While SFN silencing exerts converse effects on HCC progression. Additionally, we unveil a critical interaction between SFN and AKT, where SFN boosts AKT kinase activity by disrupting the binding of PHLPP2 and AKT, thereby intensifying the malignant progression of HCC cells. In conclusion, this study identifies the oncogenic role of SFN and elucidates the regulatory mechanism of the SFN/AKT axis in HCC, which may provide valuable insights into the mechanisms of HCC progression and potential targets for therapeutic intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In the realm of organic synthesis, the catalytic and stereoselective formation of C-glycosidic bonds is a pivotal process, bridging carbohydrates with aglycones. However, the inherent chirality of the saccharide scaffold often has a substantial impact on the stereoinduction imposed by a chiral ligand. In this study, we have established an unprecedented zirconaaziridine-mediated asymmetric nickel catalysis, enabling the diastereoselective coupling of bench-stable glycosyl phosphates with a range of (hetero)aromatic and glycal iodides as feasible coupling electrophiles. Our developed method showcases a broad scope and a high tolerance for various functional groups. More importantly, precise stereocontrol toward both anomeric configurations of forming C(sp 2 )-glycosides can be realized by simply utilizing the popular chiral bioxazoline (biOx) ligands in this reductive Ni catalysis. Regarding the operating mechanism, both experimental and computational studies support the occurrence of a redox transmetalation process, leading to the formation of a transient, bimetallic Ni-Zr species that acts as a potent and efficient single-electron reductant in the catalytic process.

Background: Ergothioneine (EGT) is an antioxidant, which could be detected in human tissues, and human skin cells could utilize EGT and play an anti-oxidative role in keratinocytes. And in this study we are going to elucidate whether EGT could protect the skin from photoaging by Ultraviolet (UV) exposure in mice and its molecule pathway., Methods: Histological analysis was performed for evaluating the skin structure change. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured with biological assay for evaluating oxidative and antioxidative ability of skin exposed to UV light. And the level of marker molecules in mouse skin were detected by hydroxyproline (Hyp) assay, immunohistochemical analysis, Western blot, and quantitative real-time PCR (qRT-PCR). The markers of skin aging and cell death were tested by cell culture and treatment, Western blot and qRT-PCR., Results: EGT decreased the levels of inflammatory factors induced by UV exposure in mouse skin. MDA and SOD activity detection showed that EGT decreased MDA levels, increased SOD activity, and upregulated PI3K/Akt/Nrf2 signals in mouse skin exposed to UV, which further activated Nrf2 in the nucleus and enhanced the expression of Nrf2 target genes. In the cell model, we revealed that EGT could inhibit the increase in senescence-associated β-galactosidase-positive cells and p16 and γ-H2A.X positive cells induced by etoposide and activate PI3K/Akt/Nrf2 signaling. Moreover, a PI3K inhibitor blocked EGT protection against etoposide-induced cell death., Conclusion: The study showed EGT may play an important protective role against cell damage or death through the PI3K/Akt/Nrf2 signaling pathway in skin., Competing Interests: Ergothioneine production patent (WO-2014100752-A1) has been assigned from Boston University to Ergo-health LLC and Pinghua Liu is one of the co-founders of Ergo-health. The authors declare that they have no other competing interests in this work., (© 2024 Li et al.)

Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuates older HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated in older livers, especially during HIRI. Overexpressing FTO improves older HIRI phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) and transferrin receptor protein 1 (TFRC), two key positive contributors to ferroptosis, are FTO targets. For ameliorative effect, FTO requires the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrate nicotinamide mononucleotide can upregulate FTO demethylase activity, suppressing ferroptosis and decreasing older HIRI. Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO to improve graft function after older donor liver transplantation., (© 2024. The Author(s).)

In this study, a potassium ferrate (K 2 FeO 4 )-modified biochar (Fe-BC) was prepared and characterized. Afterwards, Fe-BC was applied to activated periodate (PI) to degrade tetracycline (TC), an antibiotic widely used in animal farming. The degradation effects of different systems on TC were compared and the influencing factors were investigated. In addition, several reactive oxygen species (ROS) generated by the Fe-BC/PI system were identified, and TC degradation pathways were analyzed. Moreover, the reuse performance of Fe-BC was evaluated. The results exhibited that the Fe-BC/PI system could remove almost 100% of TC under optimal conditions of [BC] = 1.09 g/L, initial [PI] = 3.29 g/L, and initial [TC] = 20.3 mg/L. Cl - , HCO 3 - , NO 3 - , and humic acid inhibited TC degradation to varying degrees in the Fe-BC/PI system due to their quenching effects on ROS. TC was degraded into intermediates and even water and carbon dioxide by the synergistic effect of ROS generated and Fe on the BC surface. Fe-BC was reused four times, and the removal rate of TC was still maintained above 80%, indicating the stable nature of Fe-BC., Competing Interests: The authors declare there is no conflict., (© 2024 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY-NC-ND 4.0), which permits copying and redistribution for non-commercial purposes with no derivatives, provided the original work is properly cited (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Calophaca sinica is a rare plant endemic to northern China which belongs to the Fabaceae family and possesses rich nutritional value. To support the preservation of the genetic resources of this plant, we have successfully generated a high-quality genome of C. sinica (1.06 Gb). Notably, transposable elements (TEs) constituted ~73% of the genome, with long terminal repeat retrotransposons (LTR-RTs) dominating this group of elements (~54% of the genome). The average intron length of the C. sinica genome was noticeably longer than what has been observed for closely related species. The expansion of LTR-RTs and elongated introns emerged had the largest influence on the enlarged genome size of C. sinica in comparison to other Fabaceae species. The proliferation of TEs could be explained by certain modes of gene duplication, namely, whole genome duplication (WGD) and dispersed duplication (DSD). Gene family expansion, which was found to enhance genes associated with metabolism, genetic maintenance, and environmental stress resistance, was a result of transposed duplicated genes (TRD) and WGD. The presented genomic analysis sheds light on the genetic architecture of C. sinica, as well as provides a starting point for future evolutionary biology, ecology, and functional genomics studies centred around C. sinica and closely related species., (© The Author(s) 2024. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

Background: This bibliometric analysis explored the knowledge structure of and research trends in the relationship between light and myopia., Methods: Relevant literature published from 1981 to 2024 was collected from the Web of Science Core Collection database. Visual maps were generated using CiteSpace and VOSviewer. We analyzed the included studies in terms of the annual publication count, countries, institutional affiliations, prolific authors, source journals, top 10 most cited articles, keyword co-occurrence, and cocitations., Results: A total of 525 papers examining the relationship between light and myopia published between 1981 and 2024 were collected. The United States ranked first in terms of the number of publications and actively engaged in international cooperation with other countries. The New England College of Optometry, which is located in the United States, was the most active institution and ranked first in terms of the number of publications. Schaeffel Frank was the most prolific author. The most active journal in the field was Investigative Ophthalmology & Visual Science. The most frequently cited paper in the included studies was written by Saw, SM and was published in 2002. The most common keywords in basic research included "refractive error," "longitudinal chromatic aberration," and "compensation." The most common keywords in clinical research mainly included "light exposure," "school," and "outdoor activity." The current research hotspots in this field are "progression," "refractive development," and "light exposure." The cocitation analysis generated 17 clusters., Conclusion: This study is the first to use bibliometric methods to analyze existing research on the relationship between light and myopia. In recent years, the intensity and wavelength of light have become research hotspots in the field. Further research on light of different intensities and wavelengths may provide new perspectives in the future for designing more effective treatments and interventions to reduce the incidence of myopia., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To investigate the correlation between socioeconomic status (SES) and the incidence of hypertension among adults aged 18 or above in southwest China., Methods: A multistage proportional stratified cluster sampling method was employed to recruited 9280 adult residents from 12 counties in southwest China, with all participants in the cohort tracked from 2016 to 2020. The questionnaire survey gathered information on demographics, lifestyle habits, and household income. The physical exam recorded height, weight, and blood pressure. Biochemical tests measured cholesterol levels. The chi-square test was employed to assess the statistical differences among categorical variables, while the Cox proportional hazards regression model was applied to evaluate the association between socioeconomic status (SES) and the incidence of hypertension., Results: The finally effective sample size for the cohort study was 3546 participants, after excluding 5734 people who met the exclusion criteria. Adults in the highest household income group had a significantly lower risk of hypertension compared to those in the lowest income group (HR = 0.636, 95% CI: 0.478-0.845). Besides, when compared to individuals in the illiterate population, the risk of hypertension among adults with elementary school, junior high school, senior high school and associate degree educational level decreased respectively by 34.4% (HR = 0.656, 95%CI: 0.533-0.807), 44.9% (HR = 0.551, 95%CI: 0.436-0.697), 44.9% (HR = 0.551, 95%CI: 0.405-0.750), 46.1% (HR = 0.539, 95%CI: 0. 340-0.854). After conducting a thorough analysis of socioeconomic status, compared with individuals with a score of 6 or less, the risk of hypertension in participants with scores of 8, 10, 11, 12, and greater than 12 decreased respectively by 23.9% (HR = 0.761, 95%CI: 0.598-0.969), 29.7% (HR = 0.703, 95%CI: 0.538-0.919), 34.0% (HR = 0.660, 95%CI: 0.492-0.885), 34.3% (HR = 0.657, 95%CI: 0.447-0.967), 43.9% (HR = 0.561, 95%CI: 0.409-0.769)., Conclusion: The findings indicate a negative correlation between socioeconomic status and hypertension incidence among adults in southwest China, suggesting that individuals with higher socioeconomic status are less likely to develop hypertension., (© 2024. The Author(s).)

Background: Curcubita ficifolia Bouché (Cucurbitaceae) has high value as a food crop and medicinal plant, and also has horticultural value as rootstock for other melon species. China is home to many different cultivars, but the genetic diversity of these resources and the evolutionary relationships among them, as well as the differences between C. ficifolia and other Cucurbita species, remain unclear., Results: We investigated the chloroplast (cp) genomes of 160 C. ficifolia individuals from 31 populations in Yunnan, a major C. ficifolia production area in China. We found that the cp genome of C. ficifolia is ~151 kb and contains 128 genes, of which 86 are protein coding genes, 34 encode tRNA, and eight encode rRNAs. We also identified 64 SSRs, mainly AT repeats. The cp genome was found to contain a total of 204 SNP and 57 indels, and a total of 21 haplotypes were found in the 160 study individuals. The reverse repeat (IR) region of C. ficifolia contained a few differences compared with this region in the six other Cucurbita species. Sequence difference analysis demonstrated that most of the variable regions were concentrated in the single copy (SC) region. Moreover, the sequences of the coding regions were found to be more similar among species than those of the non-coding regions. The phylogenies reconstructed from the cp genomes of 61 representative species of Cucurbitaceae reflected the currently accepted classification, in which C. ficifolia is sister to the other Cucurbita species, however, different interspecific relationships were found between Cucurbita species., Conclusions: These results will be valuable in the classification of C. ficifolia genetic resources and will contribute to our understanding of evolutionary relationships within the genus Cucurbita., (© 2024. The Author(s).)

The accumulation of lanthanide fission products carries the risk of altering the structure and properties of the nuclear fuel carrier salt LiF-BeF 2 (Flibe), thereby downgrading the operating efficiency and safety of the molten salt reactor. However, the condition-limited experimental measurements, spatiotemporal-limited first-principles calculations, and accuracy-limited classical dynamic simulations are unable to capture the precise local structure and reliable thermophysical properties of heterogeneous molten salts. Therefore, the deep potential (DP) of LaF 3 and Flibe molten mixtures is developed here, and DP molecular dynamics simulations are performed to systemically study the densities, diffusion coefficients, viscosities, radial distribution functions and coordination numbers of multiple molten Flibe + x LaF 3 , the quantitative relationships between these properties and LaF 3 concentration are investigated, and the potential structure-property relationships are analyzed. Eventually, the transferability of DP on molten Flibe + LaF 3 with different formulations as well as the predictability of structures and properties are achieved at the nanometer spatial scale and the nanosecond timescale.

Background and Aims: To investigate the impact of intrahepatic cholestasis of pregnancy (ICP) with hepatitis B virus (HBV) infection on pregnancy outcomes., Methods: We selected 512 pregnant women, collected the data including maternal demographics, main adverse pregnancy outcomes and maternal HBV infected markers HBeAg and HBV-DNA loads status, then have a comparative analysis., Results: There were 319 solitary ICP patients without HBV infection (Group I) and 193 ICP patients with HBV infection. Of the latter, there were 118 cases with abnormal liver function(Group II) and 80 cases with normal liver function(Group III). All HBV-infected pregnant women with ICP were divided into hepatitis Be antigen (HBeAg)-positive group (102 cases) and HBeAg-negative group (91 cases), according to the level of the serum HBeAg status; and into high viral load group (92 cases), moderate viral load group (46 cases) and low viral load group (55 cases) according to the maternal HBV-DNA level. Group II had a higher level of serum total bile acids, transaminase, bilirubin as well as a higher percentage of premature delivery, neonatal intensive care unit (NICU) admission and meconium-stained amniotic fluid (MSAF) compared with the other two groups(P < 0.05), but there were no significant differences in the above indicators between the Group I and Group III. Among the HBV-infected patients with ICP, HBeAg-positive group had a higher level of serum transaminase, bilirubin and bile acid as well as earlier gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission than HBeAg-negative group (P < 0.05). Those with a high viral load (HBV-DNA > 10 6  IU/ml) had a higher level of transaminase, bilirubin, and bile acid as well as shorter gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission compared with those with a low or moderate viral load (P < 0.05)., Conclusion: HBV-infected pregnant women with ICP combined with abnormal liver function have more severe liver damage, a higher percentage of preterm birth and NICU admission. HBeAg-positive status and a high HBV-DNA load will increase the severity of conditions in HBV-infected pregnant women with ICP. HBV-infected patients with ICP who have abnormal liver function, HBeAg-positive or a high viral load should be treated more actively., (© 2024. The Author(s).)

Ischemic strokes, prevalence and impactful, underscore the necessity of advanced research models closely resembling human physiology. Our study utilizes nonhuman primates (NHPs) to provide a detailed exploration of ischemic stroke, integrating neuroimaging data, behavioral outcomes, and serum proteomics to elucidate the complex interplay of factors involved in stroke pathophysiology. We observed a consistent pattern in infarct volume, peaking at 1-month postmiddle cerebral artery occlusion (MCAO) and then stabilized. This pattern was strongly correlated to notable changes in motor function and working memory performance. Using diffusion tensor imaging (DTI), we detected significant alterations in fractional anisotropy (FA) and mean diffusivity (MD) values, signaling microstructural changes in the brain. These alterations closely correlated with the neurological and cognitive deficits that we observed, highlighting the sensitivity of DTI metrics in stroke assessment. Behaviorally, the monkeys exhibited a reliance on their unaffected limb for compensatory movements, a common response to stroke impairment. This adaptation, along with consistent DTI findings, suggests a significant impact of stroke on motor function and spatial perception. Proteomic analysis through MS/MS functional enrichment identified two distinct groups of proteins with significant changes post-MCAO. Notably, MMP9, THBS1, MB, PFN1, and YWHAZ were identified as potential biomarkers and therapeutic targets for ischemic stroke. Our results underscore the complex nature of stroke and advocate for an integrated approach, combining neuroimaging, behavioral studies, and proteomics, for advancing our understanding and treatment of this condition.

Objective: This study aimed to evaluate the management effect of music therapy on the psychological health of patients undergoing maintenance hemodialysis (MHD), with focus on improving levels of depression, anxiety and stress., Methods: A retrospective analysis of clinical data was conducted for 218 patients with sleep disorders accompanied by hemodialysis (HD) from January 2020 to December 2023. The subjects were categorized into a control group comprising 122 cases and an observational group comprising 96 cases. The observation group received music therapy in addition to routine management for 3 months. The psychological health status of patients was assessed using the Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Hemodialysis Stressor Scale (HSS), among other indicators. t Tests, χ2 test and Wilcoxon test were performed., Results: After 3 months, the SDS and SAS scores of the observation group were significantly lower than those of the control group (P < 0.05). The scores for the "psychological stressors," "physiological stressors" and "social stressors" dimensions of HSS were also significantly lower in the observation group compared with those in the control group (P < 0.05). The overall satisfaction rate of the observation group was significantly higher than that of the control group (96.88% vs. 88.52%, P = 0.022)., Conclusion: Music therapy exerted a positive effect on improving the psychological health of HD patients, particularly in reducing stress levels. This study provides clinical evidence for music therapy as a low-cost and effective adjunctive treatment., (Copyright © 2024 Noise & Health.)

Aim: To elaborate the underlying mechanisms by which IL-1β promote progression of Dry eye disease(DED) through effect on pyroptosis and apoptosis of corneal epithelial cells(CECs)., Methods: 400 mOsM solutions were used to establish the DED model (hCECs- DED). RT-qPCR was performed to measure IL-1β mRNA and miR-146a-5p in CECs. Western blotting was performed to measure STAT3, GSDMD, NLRP3, and Caspase-1 levels. Cell counting kit-8 assay was adopted to check cell viability. Apoptosis was detected by flow cytometry. ELISAs were performed to determine IL-18, IL-33 and LDH. The luciferase test detects targeting relationships., Results: After treatment with 400 mOsM solution, cell viability decreased and apoptosis increased. Compared with hCECs, IL-1β was increased and miR-146a-5p was decreased in hCECs-DED. At the same time, GSDMD, NLRP3, Caspase-1, IL-18, IL-33 and LDH were significantly higher in hCECs-DED than in hCECs, while IL-1β silencing reversed this effect. In addition, IL-1β negatively regulated miR-146a-5p. MiR-146a-5p mimics eliminated the inhibition of hCECs-DED pyroptosis and apoptosis caused by IL-1β silencing. At the same time, miR-146a-5p reduced STAT3 levels in hCECs., Conclusion: Highly expressed IL-1β promoted pyroptosis and apoptosis of hCECs- DED through downregulated miR-146a-5p and inhibited STAT3., (© 2024. The Author(s).)

Background: Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion., Methods: Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation., Results: Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD)., Conclusions: YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Acute rejection (AR) after liver transplantation (LT) remains an important factor affecting the prognosis of patients. CD8 + T cells are considered to be important regulatory T lymphocytes involved in AR after LT. Our previous study confirmed that autophagy mediated AR by promoting activation and proliferation of CD8 + T cells. However, the underlying mechanisms regulating autophagy in CD8 + T cells during AR remain unclear., Methods: Human liver biopsy specimens of AR after orthotopic LT were collected to assess the relationship between JNK and CD8 + T cells autophagy. The effect of JNK inhibition on CD8 + T cells autophagy and its role in AR were further examined in rats. Besides, the underlying mechanisms how JNK regulated the autophagy of CD8 + T cells were further explored., Results: The expression of JNK is positive correlated with the autophagy level of CD8 + T cells in AR patients. And similar findings were obtained in rats after LT. Further, JNK inhibitor remarkably inhibited the autophagy of CD8 + T cells in rat LT recipients. In addition, administration of JNK inhibitor significantly attenuated AR injury by promoting the apoptosis and downregulating the function of CD8 + T cells. Mechanistically, JNK may activate the autophagy of CD8 + T cells through upregulating BECN1 by inhibiting the formation of Bcl-2/BECN1 complex., Conclusion: JNK signaling promoted CD8 + T cells autophagy to mediate AR after LT, providing a theoretical basis for finding new drug targets for the prevention and treatment of AR after LT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zhu, Chen, Li, Zheng, Zhang, Fan, Chen and Wang.)

Herein, using an electrophoretic deposition strategy, a S-scheme CdS (cubic)/BiVO 4 (monoclinic) heterostructured photocatalyst is fabricated. The as-synthesized photocatalysts exhibit high carrier separation efficiency, prominent hydrogen evolution ability and high stability. The results of the detailed density functional theory (DFT) prove that the photogenerated electrons and holes are located in BiVO 4 and CdS components, respectively. Besides, an explicit solvent model based on the electron-enriched region in CdS/BiVO 4 heterojunction is designed deliberately to investigate the solid/liquid interface issues. Intriguing findings demonstrate that the surface hydrogen diffusing rate in CdS/BiVO 4 /H 2 O is faster than that of BiVO 4 /H 2 O and is highly associated with the electron-enrich effect, which has a greater capacity to promote water decomposition, the possibility of proton collision and photocatalytic hydrogen evolution. Notably, the H p orbital can participate in the electron-enrich effect during solvation, thus reforming the orbital energy level and activating the HER of the BiVO 4 component in the CdS/BiVO 4 system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Panax notoginseng (Burk) F. H. Chen is one of the most famous Chinese traditional medicinal plants. The taproot is the main organ producing triterpenoid saponins, and its development is directly linked to the quality and yield of the harvested P. notoginseng. However, the mechanisms underlying the dynamic metabolic changes occurring during taproot development of P. notoginseng are unknown., Results: We carried out metabolomic and transcriptomic analyses to investigate metabolites and gene expression during the development of P. notoginseng taproots. The differentially accumulated metabolites included amino acids and derivatives, nucleotides and derivatives, and lipids in 1-year-old taproots, flavonoids and terpenoids in 2- and 3-year-old taproots, and phenolic acids in 3-year-old taproots. The differentially expressed genes (DEGs) are related to phenylpropanoid biosynthesis, metabolic pathway and biosynthesis of secondary metabolites at all three developmental stages. Integrative analysis revealed that the phenylpropanoid biosynthesis pathway was involved in not only the development of but also metabolic changes in P. notoginseng taproots. Moreover, significant accumulation of triterpenoid saponins in 2- and 3-year-old taproots was highly correlated with the up-regulated expression of cytochrome P450s and uridine diphosphate-dependent glycosyltransferases genes. Additionally, a gene encoding RNase-like major storage protein was identified to play a dual role in the development of P. notoginseng taproots and their triterpenoid saponins synthesis., Conclusions: These results elucidate the molecular mechanism underlying the accumulation of and change relationship between primary and secondary metabolites in P. notoginseng taproots, and provide a basis for the quality control and genetic improvement of P. notoginseng., (© 2024. The Author(s).)

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is the most prominent analytical platform for the exploration of novel active compounds from complex matrices. However, the LC-HRMS-based analysis workflow suffers from several bottleneck issues, such as trace content of target compounds, limited acquisition for fragment information, and uncertainty in interpreting relevant MS 2 spectra. Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus, while the reported structures are merely focused on dicaffeoylspermidines due to their low content. To comprehensively detect the new structures of lycibarbarspermidine derivatives, a "depict" strategy was developed in this study. First, potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway, and a comprehensive database was established, which enlarged the coverage of lycibarbarspermidine derivatives. Second, the polarity-oriented sample preparation of potential new compounds increased the concentration of the target compounds. Third, the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification. Finally, the weak response signals were captured by data-dependent scanning (DDA) followed by parallel reaction monitoring (PRM), and the efficiency of acquiring MS 2 fragment ions of target compounds was significantly improved. Based on the integrated strategy above, 210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus, and in particular, 170 potential new compounds were structurally characterized. The integrated strategy improved the sensitivity of detection and the coverage of low-response components, and it is expected to be a promising pipeline for discovering new compounds., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Objectives: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with severe type II respiratory failure have a high probability of ventilation failure using conventional non-invasive positive pressure ventilation (NPPV). This study aims to investigate the clinical efficacy of high intensity NPPV (HI-NPPV) for the treatment of AECOPD combined with severe type II respiratory failure., Methods: The data of patients with AECOPD combined with severe type II respiratory failure (blood gas analysis pH≤7.25) treated with NPPV in the Second Affiliated Hospital of Chongqing Medical University from July 2013 to July 2023 were collected to conduct a retrospective case-control study. The patients were divided into 2 groups according to the inspired positive airway pressure (IPAP) used during the NPPV treatment: a NPPV group (IPAP<20 cmH 2 O, 1 cmH 2 O=0.098 kPa) and a HI-NPPV group (20 cmH 2 O≤IPAP< 30 cmH 2 O). Ninety-nine and 95 patients were included in the NPPV group and the HI-NPPV group, respectively. A total of 86 pairs of data were matched using propensity score matching (PSM) for data matching. The primary outcome indexes (mortality and tracheal intubation rate) and secondary outcome indexes [blood gas analysis pH, arterial partial pressure of oxygen (PaO 2 ) and arterial partial pressure of carbon dioxide (PaCO 2 ), adverse reaction rate, and length of hospitalization] were compared between the 2 groups., Results: The tracheal intubation rates of the NPPV group and the HI-NPPV group were 6.98% and 1.16%, respectively, and the difference between the 2 groups was statistically significant ( χ 2 =4.32, P <0.05); the mortality of the NPPV group and the HI-NPPV group was 23.26% and 9.30%, respectively, and the difference between the 2 groups was statistically significant ( χ 2 =11.64, P <0.01). The PaO 2 at 24 h and 48 h after treatment of the HI-NPPV group was higher than that of the NPPV group, and the PaCO 2 of the HI-NPPV group was lower than that of the NPPV group, and the differences were statistically significant (all P <0.05). The differences of pH at 24 h and 48 h after treatment between the 2 groups were not statistically significant (both P >0.05). The differences between the 2 groups in adverse reaction rate and hospitalization length were not statistically significant (both P >0.05)., Conclusions: HI-NPPV can reduce mortality and tracheal intubation rates by rapidly improving the ventilation of patients with AECOPD combined with severe type II respiratory failure. This study provides a new idea for the treatment of patients with AECOPD combined with severe type II respiratory failure.

Two new compounds ( R )-6-((8 S )-hydroxypropyl)-2-methyl-5,6-dihydro-4 H -pyran-4-one ( 1 ) and ( R )-6-((8 R )-hydroxypropyl)-2-methyl-5,6-dihydro-4 H -pyran-4-one ( 2 ), together with four known compounds were isolated from the marine-derived fungus Cladosporium halotolerans FS702. The structures of these compounds were determined on the basis of extensive spectroscopic analysis including 1D/2D NMR, IR, UV, HRESIMS, ECD calculations as well as the modified Mosher's method. Cytotoxic assay results showed that compound 2 had significant cytotoxic activity against SF-268, MCF-7, HepG-2, and A549 cells lines with IC 50 values of 0.16, 0.47, 0.33 and 0.23 µM, respectively.

Aquaporin-4 (AQP4) is essential for normal functioning of the brain's glymphatic system. Impaired glymphatic function is associated with neuroinflammation. Recent clinical evidence suggests the involvement of glymphatic dysfunction in LRRK2-associated Parkinson's disease (PD); however, the precise mechanism remains unclear. The pro-inflammatory cytokine interferon (IFN) γ interacts with LRRK2 to induce neuroinflammation. Therefore, we examined the AQP4-dependent glymphatic system's role in IFNγ-mediated neuroinflammation in LRRK2-associated PD. We found that LRRK2 interacts with and phosphorylates AQP4 in vitro and in vivo. AQP4 phosphorylation by LRRK2 R1441G induced AQP4 depolarization and disrupted glymphatic IFNγ clearance. Exogeneous IFNγ significantly increased astrocyte expression of IFNγ receptor, amplified AQP4 depolarization, and exacerbated neuroinflammation in R1441G transgenic mice. Conversely, inhibiting LRRK2 restored AQP4 polarity, improved glymphatic function, and reduced IFNγ-mediated neuroinflammation and dopaminergic neurodegeneration. Our findings establish a link between LRRK2-mediated AQP4 phosphorylation and IFNγ-mediated neuroinflammation in LRRK2-associated PD, guiding the development of LRRK2 targeting therapy., (© 2024. The Author(s).)

Rationale: Connective tissue disease (CTD) is a heterogeneous group of chronic inflammatory autoimmune disorders derived from a systemically auto-immunological deregulation. CTD may affect cardiac structures through multiple pathophysiological mechanisms, and subclinical cardiac injury is common. Heart failure (HF) is one of the common complications in these patients., Patient Concerns: Patients with CTD suffer an increased risk of cardiovascular disease and may have chest pain and shortness of breath., Diagnosis: HF is characterized by dyspnea or exertional limitation due to impaired ventricular filling and/or blood ejection. HF can be caused by other systemic diseases, not only by cardiovascular disorders but CTD. CTD may cause HF due to diffuse myocardial damage, heart valve damage, coronary ischemia, and so on., Interventions: The patient with catastrophic antiphospholipid syndrome take prednisone and warfarin. The patient with anti-synthetase syndrome was treated with immunoglobulin, followed by long-term oral medicines of prednisone, methotrexate, and folic acid., Outcomes: The symptoms of chest pain and shortness of breath for patients with CTD improved., Lessons: HF is one of the common complications in these patients with CTD, which has poor prognosis and severe aggravation. Once such patients experience chest pain, chest tightness, shortness of breath, etc, we should consider the possibility of HF. Early identification and correct treatment can delay the progression of HF, improve the prognosis, and enhance the quality of life for patients. Therefore, we should pay more attention to patients with CTD combined with HF., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Podophyllotoxin (PPT) is a naturally occurring aryltetralin lignan. However, its clinical application has been limited due to its neurotoxicity, the mechanism of which remains unclear. This study aimed to investigate the potential involvement of the microbiota-gut-brain (MGB) axis in PPT-induced neurotoxicity using the toxicological evidence chain concept. Our approach included behavioral testing in rats, evaluation of colon and hippocampal pathological changes, examination of proinflammatory factors, brain-gut peptides, and an in-depth analysis of gut microbiome and metabolic profiles. Our results demonstrated that PPT exposure compromised cognitive functions, induced damage to the colon and hippocampus, and increased intestinal permeability in rats. Furthermore, it elevated proinflammatory factors, particularly TNF-α and IL-6, while causing disruptions in the gut microbiota, favoring Escherichia-Shigella over Lactobacillus. Significant alterations in metabolic profiles in feces, serum, and hippocampus, particularly in tryptophan metabolism with a correlation to inflammatory factors and Escherichia-Shigella, were also observed. Our findings suggest that PPT promotes the enrichment of Escherichia-Shigella leading to inflammatory factor production and alterations in kynurenine metabolism in the hippocampus, potentially contributing to neurotoxicity. The study provides novel insights into the mechanistic pathways of PPT-induced neurotoxicity, emphasizing the role of the MGB axis and offering avenues for therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Three new compounds phomtersines A-C (1-3) together with nine known compounds were isolated from the marine-derived fungus Phomopsis tersa FS441. Their structures were sufficiently established by spectroscopic methods, including extensive 1D and 2D NMR techniques and modified Snatzke's method. Moreover, compounds 1-12 were evaluated for cytotoxic and anti-inflammatory activities. As a result, phomtersine B (2) and the known compound 10 showed moderate cytotoxic activity against the four tested cell lines with IC 50 values ranging from 20.21 to 36.53 μM, and phomtersine A (1) exhibited moderate inhibitory activity against LPS-induced NO production., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In the realm of photocatalysis, understanding the interface issues (solid/solid and solid/liquid) inherent in heterojunction at the atomic level is the ultimate for engineering an efficient photocatalyst. Herein, an electrophoretic deposition technique is adopted to synthesize BiOI/β-Bi 2 O 3 heterojunction, exhibiting superior photocatalytic activity and stability in H 2 evolution (91.5 μmol g -1 h -1 ) and H 2 O 2 production (11.3 mg L -1 h -1 ). Combined with the experimental and computational results, a lower free energy of hydrogen evolution reaction (252.4 meV) has been observed contrast to BiOI and β-Bi 2 O 3 samples. A carrier transfer process of like S-scheme heterojunction is proposed based on density of states (DOS) and carrier distribution calculations. The theoretical calculations illustrate the transition dipole moment, migration and accumulation of carrier in BiOI/β-Bi 2 O 3 heterojunction. Subsequent ab initio molecular dynamics (AIMD) results of solid/liquid interface systems (BiOI/β-Bi 2 O 3 /H 2 O and β-Bi 2 O 3 /H 2 O) unravel the interface H 2 O (solvent) behaviors. The local aggregation of photo-generated electrons in BiOI/β-Bi 2 O 3 /H 2 O leads to a large potential drop, high proton migration rate and the steady electric double layer (EDL) structure compared to the β-Bi 2 O 3 /H 2 O, which facilitates the occurrence of photocatalytic reactions in solution. In addition to offering new insights into the hydrogen evolution and proton transfer in the EDL model and the association between the heterojunction effect and EDL structure, this work also introduces a novel design strategy for Bi-based heterojunctions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is increasing interest in developing quinoa products due to their unique nutritional value. Starch and protein are the primary components in quinoa, and the interaction between them affects the quality of quinoa products. This study extracted the starch and protein from quinoa and simulated the thermal processing of quinoa to investigate the effects of starch on the solubility and structure of quinoa protein isolates during heat treatment. The structure of quinoa protein isolates was characterized by fluorescence spectroscopy, Fourier transform infrared spectroscopy, laser particle size analysis, and scanning electron microscopy. The results showed that starch decreased protein solubility, and the maximum solubility was obtained after heating for 5 min. After starch addition during heat treatment, the surface charge distribution of protein changed, the degree of protein aggregation increased, the particle size of proteins increased, the thermal stability increased, and the β-sheet ratio of the proteins increased, suggesting that the protein structure is more ordered, which is the structural foundation of protein solubility decreasing. The research about the interaction between starch and protein and the effects on the solubility of protein could provide a reference for quinoa products processing.

The effect of the combination of 10-Hydroxycamptothecin (HCPT) and crizotinib (CRI) on EGFR- and KRAS-mutant lung cancer cells was investigated and the conjugates of the two drugs were synthesised. HCPT combined with CRI synergistically inhibited the cell growth and proliferation of H1975, HCC827, and H460 without aggravating adverse effect on the normal cells. The combination synergistically enhanced the cell apoptosis rate through releasing Cyto-C by activation of Bcl-2 family-mediated mitochondrial signalling, which was associate with inactivating of EGFR related downstream signalling pathways including AKT, ERK, JNK, and p38 MAPK. Based on this synergy, the conjugates of HCPT and CRI (compounds CH-1 and CH-2 ) with different chemical bonds were synthesised. Compound CH-1 exhibited stronger cytotoxicity than HCPT and CRI alone or in combination. The combination of HCPT and CRI might be a promising therapeutic regimen and the conjugate CH-1 was a potential target drug for the treatment of lung cancer.

It has been established that monotherapy yields limited efficacy in treating hepatocellular carcinoma (HCC), especially advanced HCC. Increasing evidence from preclinical studies and clinical trials indicates that combining multiple drugs can potentially refine treatment efficacy. Accordingly, it is crucial to explore more effective clinically feasible combination therapies to enhance the treatment outcomes of HCC patients. This study evaluated the antitumor efficacy and safety of combination therapy involving aspirin and lenvatinib in HCC. Through in vitro and in vivo assays, we demonstrated that this combination yielded stronger antitumor effects compared to lenvatinib or aspirin monotherapy. Furthermore, no significant adverse events were observed in an HCC mouse model during treatment. Mechanistic studies revealed that aspirin plus lenvatinib could target multiple oncogenes and tumor suppressors, affecting diverse signaling pathways in various biological processes conducive to antitumor effects. Overall, our findings suggest that aspirin plus lenvatinib could serve as a promising combination regimen to improve the therapeutic outcomes of HCC., (© 2023. The Author(s).)

Colorectal cancer (CRC) is a common malignant tumor with a high incidence and mortality worldwide. Preoperative chemoradiotherapy is a common treatment for patients with metastatic colorectal cancer (mCRC) as it reduces colostomy and local recurrence. The RAS (rat sarcoma)-RAF (extracellular signal-regulated kinase)-MEK (mitogen-activated protein kinase)-ERK (extracellular signal-regulated kinase) pathway regulates important cellular processes in the CRC. Abnormal ERK activation stimulates cell growth and provides a survival advantage. Our group has previously reported that the compound KZ02 has a stronger ability to inhibit tumor growth than AZD6244 (a MEK inhibitor). In this study, we evaluated the antitumor activity of KZ02 in combination with ionizing radiation (IR) and investigated its mechanism of action in BRAF-mutated colorectal cancer. Our results showed that this combination kills tumor cells better than either radiation or drugs alone, both in vivo and in vitro. Furthermore, studies have shown that KZ02 inhibits ERK overactivation. The combination resulted in a G1 phase arrest, a reduction in the radioresistant S phase, and aggravating DNA damage. It can also inhibit Pim-1 (Moloney murine leukemia virus-1), p-BAD (Bcl-2 associated agonist of cell death), Bcl-2 (B-cell lymphoma 2) and Bcl-XL (B-cell lymphoma-extra large) levels and promote apoptosis when combined with radiation. Our results suggest that KZ02 significantly increases the radiosensitivity of BRAF-mutated CRC cells by perturbing the cell cycle, increasing DNA damage, and promoting tumor apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Glycine soja Sieb. & Zucc. is the wild ancestor from which the important crop plant soybean was bred. G. soja provides important germplasm resources for the breeding and improvement of cultivated soybean crops, however the species is threatened by habitat loss and fragmentation, and is experiencing population declines across its natural range. Understanding the patterns of genetic diversity in G. soja populations can help to inform conservation practices., Methods: In this study, we analyzed the genetic diversity and differentiation of G. soja at different sites and investigated the gene flow within the species. We obtained 147 G. soja accessions collected from 16 locations across the natural range of the species from China, Korea and Japan. Samples were analyzed using SLAF-seq (Specific-Locus Amplified Fragment Sequencing)., Results: We obtained a total of 56,489 highly consistent SNPs. Our results suggested that G. soja harbors relatively high diversity and that populations of this species are highly differentiated. The populations harboring high genetic diversity, especially KR, should be considered first when devising conservation plans for the protection of G. soja , and in situ protection should be adopted in KR. G. soja populations from the Yangtze River, the Korean peninsula and northeastern China have a close relationship, although these areas are geographically disconnected. Other populations from north China clustered together. Analysis of gene flow suggested that historical migrations of G. soja may have occurred from the south northwards across the East-Asia land-bridge, but not across north China. All G. soja populations could be divided into one of two lineages, and these two lineages should be treated separately when formulating protection policies., Competing Interests: The authors declare that they have no competing interests., (© 2023 Meng et al.)

Despite being a powerful weapon against cancer cells, cisplatin's therapeutic potential is hampered by numerous adverse reactions, including acute kidney injury (AKI). Compound 5 has 3-SH fragments at the end of the vertical short alkyl side chain, which is an ROS scavenger synthesized. In this study, we evaluated the protective effect of compound 5 on the kidney after cisplatin administration and its mechanism. The results founded that compound 5 can alleviate serum urea nitrogen and serum creatinine induced by cisplatin administration in vivo. In addition, histopathological analysis of the kidneys showed that compound 5 significantly reduced cisplatin-induced (Cis-induced) renal toxicity compared with the cisplatin group. A mechanism study showed that compound 5 significantly reduces NOX4 levels, improves the activity of antioxidant enzymes (SOD and GSH-Px), reduces Malondialdehyde (MDA) levels, increases the total antioxidant level, reduces oxidative stress, and thus reduces kidney tissue damage. At the same time, compound 5 activated the Nrf2 signaling pathway. In addition, it can increase the expression of Bax, reduce the expression of Bcl-2 and caspase-3, a marker of apoptosis, which is beneficial to the survival of kidney cells. Additionally, compound 5 did not interfere with the antitumor effects of cisplatin in in vivo xenotransplantation models., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Boletus auripes is edible and medicinal boletus mushrooms rich in diverse nutrients and bioactive compounds, of which indigestible dietary polysaccharides are the most abundant compounds involved the regulation of gut microbes. However, the physicochemical, digestive, and fermentation characteristics of Boletus auripes polysaccharide (BAP) are not well studied. This study aimed to investigate the influence of different digestive stages on BAP's physicochemical characteristics and biological activities, and its effect on intestinal flora. We found that mannose (0.23 %), glucose (0.31 %), galactose (0.17 %), and fucose (0.19 %) were the main monosaccharides of BAP, with a high-molecular-weight (Mw) and a low-Mw fraction of 2084.83 and 62.93 kDa, respectively. During the course of digestion, there were slight alterations in the chemical composition, monosaccharide composition, and Mw of BAP. Despite these changes, the fundamental structural features of BAP remained largely unaffected. Moreover, the antioxidant and hypoglycemic activities of BAP were weakened under simulated saliva-gastrointestinal digestion. However, gut microbiota decomposed and utilized BAP to generate various short-chain fatty acids during fermentation, which decreased the pH of fecal cultures. Meanwhile, BAP modulated the gut microbiota composition and increased the relative abundance of Bacteroidetes. These findings suggest that BAP have potential for maintaining intestinal health and protecting against interrelated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Soybean whey and soybean hydrolyzate can be used for the biotechnological production of high-value products. Herein, we isolate soybean whey (SW)-and soybean hydrolyzate (SH)-derived bacterial cellulose (BC, produced by kombucha) and characterize it by a range of instrumental techniques to reveal differences in micromorphology, crystallinity, and themal behavior. Studies have shown that the amounts of wet state BC produced from HS, SW and SH was 181 g/L, 47 g/L and 83 g/L, respectively. The instrumental analysis of BC, included SEM, AFM, FT-IR, XRD and TGA. It is shown that the FT-IR spectra of BC have a similar character, but we found differences in the micromorphology,crystallinity and thermal temperature of BC. The minimum average widths of the fibers produced from SH medium was 100 ± 29 nm. The CrI values of BC produced from SH medium was 61.8%. The maximum thermal degradation rate temperature of BC produced from SW medium was 355.73 °C. The combined results demonstrate that soybean industrial waste can be used as a cost-effective raw material for BC production., (© 2023. Springer Nature Limited.)

The cytokinin response regulator (RR) gene is essential for cytokinin signal transduction, which plays a crucial role in plant growth and development. Here, we applied bioinformatics to Rhododendron delavayi 's genome to identify its RR gene family and systematically analyzed their gene characteristics, phylogenetic evolution, chromosomal localization, collinearity analysis, promoter cis-elements, and expression patterns. Overall, 33 RdRR genes were distinguished and classified into three types. All these genes harbored motif 5 (YEVTTVNSGLEALELLRENKB), the most conserved one, along with the plant-conserved domain (REC domain), and could be mapped to 10 chromosomes with four gene pairs of segmental replication events but no tandem replication events; 13 RdRR genes showed collinearity with Arabidopsis thaliana genes. Promoter analysis revealed multiple hormone-related cis -elements in the RR genes. After a TDZ (thidiazuron) treatment, 13 genes had higher expression levels than the control, whose magnitude of change depended on the developmental stage of leaves' adventitious buds. The expression levels of RdRR14 , RdRR17 , RdRR20 , and RdRR24 agreed with the average number of adventitious buds post-TDZ treatment. We speculate that these four genes could figure prominently in bud regeneration from R. delavayi leaves in vitro. This study provides detailed knowledge of RdRRs for research on cytokinin signaling and RdRR functioning in R. delavayi .

Iron overload often occurs during blood transfusion and iron supplementation, resulting in the presence of non-transferrin-bound iron (NTBI) in host plasma and damage to multiple organs, but effects on the intestine have rarely been reported. In this study, an iron overload mouse model with plasma NTBI was established by intraperitoneal injection of iron dextran. We found that plasma NTBI damaged intestinal morphology, caused intestinal oxidative stress injury and reactive oxygen species (ROS) accumulation, and induced intestinal epithelial cell apoptosis. In addition, plasma NTBI increased the relative abundance of Ileibacterium and Desulfovibrio in the cecum, while the relative abundance of Faecalibaculum and Romboutsia was reduced. Ileibacterium may be a potential microbial biomarker of plasma NTBI. Based on the function prediction analysis, plasma NTBI led to the weakening of intestinal microbiota function, significantly reducing the function of the extracellular structure. Further investigation into the mechanism of injury showed that iron absorption in the small intestine significantly increased in the iron group. Caco-2 cell monolayers were used as a model of the intestinal epithelium to study the mechanism of iron transport. By adding ferric ammonium citrate (FAC, plasma NTBI in physiological form) to the basolateral side, the apparent permeability coefficient (Papp) values from the basolateral to the apical side were greater than 3×10 -6 cm s -1 . Intracellular ferritin level and apical iron concentration significantly increased, and SLC39A8 (ZIP8) and SLC39A14 (ZIP14) were highly expressed in the FAC group. Short hairpin RNA (shRNA) was used to knock down ZIP8 and ZIP14 in Caco-2 cells. Transfection with ZIP14-specific shRNA decreased intracellular ferritin level and inhibited iron uptake. These results revealed that plasma NTBI may cause intestinal injury and intestinal flora dysbiosis due to the uptake of plasma NTBI from the basolateral side into the small intestine, which is probably mediated by ZIP14., (© 2023. Science China Press.)

Scutellaria baicalensis is a functional food that has the potential to treat various diseases. Scutellaria baicalensis can be divided into two types: Ziqin (strip types) and (rotten xylem). Ziqin is used to clear lower energizer large intestine heat syndrome, while Kuqin is used for the treatment of upper energizer lung heat syndrome. At present, the substance basis of the differences between Ziqin and Kuqin is not clear. The changes in metabolite accumulation and protein expression between them were analyzed by the non-targeted metabolomic technique in combination with the label-free proteomics approach. The results showed that the differentially accumulated metabolites and abundant proteins were mainly enriched in the pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylpropanoid biosynthesis, flavonoid biosynthesis, flavone and flavonol biosynthesis, isoflavonoid biosynthesis, and anthocyanin biosynthesis. Collectively, these results reveal the changes of Scutellaria baicalensis in different growth years and provide a reference for selecting the appropriate harvest period., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Phototherapy, including photothermal and photodynamic therapy, has gained extensive attention in the tumor treatment field recently, while synergistic therapy can significantly improve curative effects. However, a complicated photo-responsive nanosystem, different excitation wavelengths, and low tissue depth hindered its actual application. Herein, single near-infrared responsive PEGylated defective MoO 2 nanocrystals were fabricated by a green hydrothermal method. The photothermal and photodynamic performances of the samples were presented in detail under a safe power of 1064 nm (NIR-II, 1.0 W cm -2 ). Interestingly, the photodynamic properties were prompted by the localized surface plasmon resonance (LSPR) photothermal effect obviously, and the collaborative enhancement mechanism was explored in depth. Subsequently, the in vitro cytotoxicity was evaluated on the 4T1 cancer cells under NIR-II irradiation. This work may provide guidance for the facile fabrication of TMOs for NIR-II responsive and enhanced dual-modal phototherapy.

This study focuses on the characteristics of fractured and vuggy high-temperature and high-salt reservoirs in the Tahe Oilfield. The Acrylamide/2-acrylamide-2-methylpropanesulfonic copolymer salt was selected as a polymer; the hydroquinone and hexamethylene tetramine was selected as the crosslinking agent with a ratio of 1:1; the nanoparticle SiO 2 was selected, and its dosage was optimized to 0.3%; Additionally, a novel nanoparticle coupling polymer gel was independently synthesized. The surface of the gel was a three-dimensional network structure, with grids arranged in pieces and interlaced with each other, and the structure was very stable. The SiO 2 nanoparticles were attached to the gel skeleton, forming effective coupling and enhancing the strength of the gel skeleton. To solve the problem of complex gel preparation and transportation, the novel gel is compressed, pelletized, and dried into expanded particles through industrial granulation, and the disadvantage of the rapid expansion of expanded particles is optimized through physical film coating treatment. Finally, a novel nanoparticle coupling expanded granule plugging agent was developed. Evaluation of the performance of the novel nanoparticle coupling expanded granule plugging agent. With an increase in temperature and mineralization, the expansion multiplier of granules decreases; aged under high-temperature and high-salt conditions for 30 days, the expansion multiplier of granules can still reach 3.5 times, the toughness index is 1.61, and the long-term stability of the granules can be good; the water plugging rate of granules is 97.84%, which is superior to other widely used particle-based plugging agents.

Background: Dysbiosis commonly occurs in pancreatic cancer, but its specific characteristics and interactions with pancreatic cancer remain obscure., Materials and Methods: The 16S rRNA sequencing method was used to analyze multisite (oral and gut) microbiota characteristics of pancreatic cancer, chronic pancreatitis, and healthy controls. Differential analysis was used to identify the pancreatic cancer-associated genera and pathways. A random forest algorithm was adopted to establish the diagnostic models for pancreatic cancer., Results: The chronic pancreatitis group exhibited the lowest microbial diversity, while no significant difference was found between the pancreatic cancer group and healthy controls group. Diagnostic models based on the characteristics of the oral (area under the curve (AUC) 0.916, 95% confidence interval (CI) 0.832-1) or gut (AUC 0.856; 95% CI 0.74, 0.972) microbiota effectively discriminate the pancreatic cancer samples in this study, suggesting saliva as a superior sample type in terms of detection efficiency and clinical compliance. Oral pathogenic genera ( Granulicatella , Peptostreptococcus , Alloprevotella , Veillonella , etc.) and gut opportunistic genera ( Prevotella , Bifidobacterium , Escherichia/Shigella , Peptostreptococcus , Actinomyces , etc.), were significantly enriched in pancreatic cancer. The 16S function prediction analysis revealed that inflammation, immune suppression, and barrier damage pathways were involved in the course of pancreatic cancer., Conclusion: This study comprehensively described the microbiota characteristics of pancreatic cancer and suggested potential microbial markers as non-invasive tools for pancreatic cancer diagnosis.

Intrauterine growth retardation (IUGR) is a major complication of pregnancy and is the second leading cause of perinatal morbidity and mortality. The etiology of IUGR is multifactorial and the maternal factors are easily identifiable and modifiable. The present study aimed to perform a meta-analysis to identify the association between various maternal factors and IUGR. Eight electronic databases (PubMed, Cochrane, Embase, CIHNAL Plus, CNKI, VIP database, CBM, and WanFang database) were searched from their inception until July 2020. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Form and the Joanna Briggs Institute critical appraisal tool were used to evaluate the quality of included studies. The outcomes of study were calculated by OR with 95%CI. The study protocol was registered with PROSPERO (No. CRD42020210615). A total of 15 studies were included, with a sample size range from 152 to 9372. The quality of included studies ranged from moderate to high. The pooled results identified seven factors: smoking (OR = 1.62, 95%CI 1.38-1.90), primiparity (OR = 1.64, 95%CI 1.20-2.24), and prepregnancy.BMI < 18.5 (OR = 1.98, 95%CI 1.29-3.03), anemia (OR = 2.01, 95%CI 1.44-2.82), hypoproteinemia (OR = 2.91, 95%CI 1.94-4.36), pregnancy-induced hypertension (OR = 3.45, 95%CI 1.80-6.58), and maternal gestational weight gain (OR = 2.51, 95%CI 1.88-3.35). The present study identified several maternal factors for IUGR: smoking, primiparity, prepregnancy BMI < 18.5, poor gestational weight gain, PIH, anemia, and hypoproteinemia. The result could serve to generate risk factors prediction models, improve the management and education for child-bearing or early pregnant women., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)