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Purpose: Bloodstream infections (BSIs) are associated with significant morbidity, mortality and costs, while prolonged blood culture (BC) diagnosis may delay the initiation of targeted therapy. This study evaluates the impact of an optimized microbiology laboratory process on turnaround times, antibiotic use, clinical outcomes and economics for hospitalized BSI patients., Methods: A pre-post study was conducted in a Chinese hospital in which BSI derived BC results before (Oct. 2020- Sep. 2021) and after (Oct. 2021- Sep. 2022) newly implemented microbiology diagnostics and workflow changes were analyzed. Turnaround times, antibiotic initiation, length of stay and in-hospital costs were compared., Results: From 213 included patients, 134 were pre-optimization (pre-op) and 79 were post-optimization (post-op) cases. The median time from blood sample collection (BSC) to pathogen identification (ID) decreased from 70.12 to 47.43 h post-op (P < 0.001). The median time from BSC to the first ID report related initiation of pathogen-directed antibiotic use decreased from 88.48 to 47.85 h post-op (P < 0.001). The average hospital stay decreased from 19.54 to 16.79 days and 30-day readmissions declined from 18.7 to 13.9%, while the mean total antimicrobial drug usage costs decreased by 3,889 CNY per patient (P = 0.022) after optimization., Conclusions: Implementing new diagnostics technologies and optimizing laboratory workflows significantly reduced antimicrobial drug usage costs, shortened the time to ID results and improved the timeliness of appropriate antibiotic choices to treat BSIs. Investments in faster testing and process improvements were clearly beneficial for patient outcomes and healthcare economics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Observational studies have discovered a contradictory phenomenon between Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between H. pylori and IBD, including ulcerative colitis (UC) and Crohn's disease (CD)., Methods: We conducted a Mendelian randomization (MR) study with two sample Genome-Wide Association Studies (GWAS) to determine whether there is a causal relationship between H. pylori infection and IBD, as well as the possible pathogenic factors that may be involved. The reliability of the main MR assumptions was examined through a series of sensitivity analyses., Results: Two genetic variants (SNPs) previously identified were employed as instrumental variables (IVs) for H. pylori infection. GWAS data for IBD, UC, and CD were obtained from the recent DF10 release10 of the FinnGen study. Our findings indicated a significant association between H. pylori seropositivity and an increased risk of IBD and UC (IBD: OR: 1.16, 95% CI, 1.03-1.31, P < 0.05; UC: OR: 1.22, 95% CI, 1.08-1.37, P < 0.001) while no causal relationship with CD ( P > 0.05). Analysis of the main virulence pathogenic factors revealed a causal relationship between cytotoxin-associated protein A (CagA) and IBD and UC (IBD: OR: 1. 06, 95% CI, 1.001-1.11, P < 0.05; UC: OR: 1.07, 95% CI, 1.004-1.14, P < 0.05), while no correlation was found for vacuolar cytotoxin A (VacA) ( P > 0.05). After applying the False Discovery Rate (FDR) correction, the causal relationship between CagA and the risk of IBD or UC was no longer statistically significant., Conclusion: This study suggests a potential causal relationship between H. pylori infection and IBD, particularly UC. The effect may be more pronounced in individuals with previous H. pylori infections., 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 Cui, Li, Zhao and Liu.)

Background: Considerable research has shown that ethnic trust reflects the existence of friendly relations among all ethnic groups and ethnic individuals, and can help in resolving ethnic conflicts and contradictions, promoting exchanges among various ethnic groups, which is highly relevant to social stability., Methods: This research, including three studies, aimed to explore the conceptual structure of ethnic trust in China, and develop and validate a measurement of the ethnic trust scale. In the first study, we used free association and in-depth interview methodology, applied cluster analysis, multidimensional scaling analysis, and grounded theory to construct the theoretical framework of Chinese people's ethnic trust concept. In the second study, we constructed an initial inventory based on the concept dimensions of ethnic trust established in the first study. We screened items by item analysis and extracted common factors using exploratory factor analysis (EFA), thus determining a total of 48 items in the two subscales (interpersonal-oriented ethnic trust subscale and the intergroup-oriented subscale), which consisted of two dimensions including particular trust and universal trust. In the third study, we used first-and second-order confirmatory factor analysis (CFA) to test the scale's construct validity., Results: The results indicated a good fit between the two-factor model and the data. And the ethnic trust scale showed very good internal consistency (Cronbach alpha >0.89) and test-retest reliability >0.70., Discussion: Based on our results, have formed a ethnic trust scale by keeping 48 items, which can beused to measure the levels of interpersonal-oriented and group-oriented ethnic trust within the Chinese cultural context., 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 Li, Yang, Liu, Wang and Mao.)

Objectives: This study aimed to examine the potential correlation between myosteatosis and the prognosis of patients diagnosed with liver cirrhosis by a meta-analysis., Methods: Cohort studies of relevance were acquired through comprehensive searches of the Medline, Web of Science, and Embase databases. To account for heterogeneity, a random-effects model was employed to combine the findings., Results: The meta-analysis included 10 retrospective and four prospective cohort studies, encompassing a total of 4287 patients diagnosed with cirrhosis. The pooled findings indicated a notable decline in transplant-free survival (TFS) among individuals with liver cirrhosis and myosteatosis compared to those without this condition (risk ratio: 1.94; 95% confidence interval: 1.61 to 2.34, p < 0.001; I2 = 49%). The predefined subgroup analyses demonstrated consistent findings across various categories, including Asian and non-Asian studies, prospective and retrospective cohort studies, patients with cirrhosis overall and those who underwent transjugular intrahepatic portosystemic shunt, studies with different follow-up durations (< or ≥ 24 months), studies employing univariate and multivariate analyses, and studies with and without an adjustment for sarcopenia (p > 0.05 for all subgroup differences). Additionally, Egger's regression test indicated the presence of significant publication bias (p = 0.044). However, trim-and-fill analysis by including three hypothesized studies showed consistent results., Conclusions: The presence of myosteatosis in individuals diagnosed with liver cirrhosis may potentially be linked to a poor TFS prognosis. Further investigations are required to ascertain whether enhancing myosteatosis could potentially yield a survival advantage for this particular patient population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tea drinks/beverage has a long history and milk is often added to enhance its taste and nutritional value, whereas the interaction between the tea bioactive compounds with proteins has not been systematically investigated. In this study, a milk-tea model was prepared by mixing green tea solution with milk and then heated at 100°C for 15 min. The milk tea was then measured using biochemical assay, antioxidant detection kit, microscopy as well as HPLC-QTOF-MS/MS after ultrafiltration. The study found that as the concentration of milk protein increased in the milk-tea system, the total phenol-protein binding rate raised from 19.63% to 51.08%, which led to a decrease in free polyphenol content. This decrease of polyphenol was also revealed in the antioxidant capacity, including 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability and ferric ion reducing antioxidant power, in a dose-dependent manner. Untargeted metabolomics results revealed that the majority of small-molecule compounds/polyphenols in tea, such as epigallocatechin gallate, (-)-epicatechin gallate, and Catechin 5,7,-di-O-gallate, bound to milk proteins and were removed by ultrafiltration after addition of milk and heat treatment. The SDS-PAGE and Native-PAGE results further indicated that small molecule compounds in tea formed covalent and non-covalent complexes by binding to milk proteins. All above results partially explained that milk proteins form conjugates with tea small-molecule compounds. Consistently, the particle size of the tea-milk system increased as the tea concentration increased, but the polymer dispersity index decreased, indicating a more uniform molecular weight distribution of the particles in the system. Addition of milk protein enhanced foam ability in the milk-tea system but reduced foam stability. In summary, our findings suggest that the proportion of milk added to tea infusion needs to be considered to maintain the quality of milk-tea from multiple perspectives, including stability, nutritional quality and antioxidant activity., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Bioelectrochemical reactions using whole-cell biocatalysts are promising carbon-neutral approaches because of their easy operation, low cost, and sustainability. Bidirectional (outward or inward) electron transfer via exoelectrogens plays the main role in driving bioelectrochemical reactions. However, the low electron transfer efficiency seriously inhibits bioelectrochemical reaction kinetics. Here, a three dimensional and artificial nanoparticles-constituent inverse opal-indium tin oxide (IO-ITO) electrode is fabricated and employed to connect with exoelectrogens (Shewanella loihica PV-4). The above electrode collected 128-fold higher cell density and exhibited a maximum current output approaching 1.5 mA cm -2 within 24 h at anode mode. By changing the IO-ITO electrode to cathode mode, the exoelectrogens exhibited the attractive ability of extracellular electron uptake to reduce fumarate and 16 times higher reverse current than the commercial carbon electrode. Notably, Fe-containing oxide nanoparticles are biologically synthesized at both sides of the outer cell membrane and probably contributed to direct electron transfer with the transmembrane c-type cytochromes. Owing to the efficient electron exchange via artificial and biosynthetic nanoparticles, bioelectrochemical CO 2 reduction is also realized at the cathode. This work not only explored the possibility of augmenting bidirectional electron transfer but also provided a new strategy to boost bioelectrochemical reactions by introducing biohybrid nanoparticles., (© 2024 Wiley‐VCH GmbH.)

Bio-photoelectrochemical cell (BPEC) is an emerging technology that can convert the solar energy into electricity or chemicals. However, traditional BPEC depending on abiotic electrodes is challenging for microbial/enzymatic catalysis because of the inefficient electron exchange. Here, electroactive bacteria (Shewanella loihica PV-4) were used to reduce graphene oxide (rGO) nanosheets and produce co-assembled rGO/Shewanella biohydrogel as a basic electrode. By adsorbing chlorophyll contained thylakoid membrane, this biohydrogel was fabricated as a photoanode that delivered maximum photocurrent 126 μA/cm 3 under visible light. Impressively, the biohydrogel could be served as a cathode in BPEC by forming coculture system with genetically edited Clostridium ljungdahlii. Under illumination, the BPEC with above photoanode and cathode yielded ∼ 5.4 mM butyrate from CO 2 reduction, 169 % increase compared to dark process. This work provided a new strategy (nanotechnology combined with synthetic biology) to achieve efficient bioelectricity and valuable chemical production in PBEC., 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 Ltd. All rights reserved.)

The use of herbal medicine as an adjuvant therapy in the management of gastric cancer has yielded encouraging outcomes, notably in enhancing overall survival rates and extending periods of disease remission. Additionally, herbal medicines have demonstrated potential anti-metastatic effects in gastric cancer. Despite these promising findings, there remains a significant gap in our understanding regarding the precise pharmacological mechanisms, the identification of specific herbal compounds, and their safety and efficacy profiles in the context of gastric cancer therapy. In addressing this knowledge deficit, the present study proposes a comprehensive exploratory analysis of the Tiao-Yuan-Tong-Wei decoction (TYTW), utilizing an integrative approach combining system pharmacology and molecular docking techniques. This investigation aims to elucidate the pharmacological actions of TYTW in gastric pathologies. It is hypothesized that the therapeutic efficacy of TYTW in counteracting gastric diseases stems from its ability to modulate key signaling pathways, thereby influencing PIK3CA activity and exerting anti-inflammatory effects. This modulation is observed predominantly in pathways such as PI3K/AKT, MAPK, and those directly associated with gastric cancer. Furthermore, the study explores how TYTW's metabolites (agrimoniin, baicalin, corosolic acid, and luteolin) interact with molecular targets like AKT1, CASP3, ESR1, IL6, PIK3CA, and PTGS2, and their subsequent impact on these critical pathways and biological processes. Therefore, this study represents preliminary research on the anticancer molecular mechanism of TYTW by performing network pharmacology and providing theoretical evidence for further experimental investigations.

This study aimed to investigate how gut microbiota dysbiosis impacts the repair of the blood-brain barrier and neurological deficits following traumatic brain injury (TBI). Through 16S rRNA sequencing analysis, we compared the gut microbiota of TBI rats and normal controls, discovering significant differences in abundance, species composition, and ecological function, potentially linked to Ghrelin-mediated brain-gut axis functionality. Further, in vivo experiments showed that fecal microbiota transplantation or Ghrelin injection could block the intracerebral TNF signaling pathway, enhance GLP-1 expression, significantly reduce brain edema post-TBI, promote the repair of the blood-brain barrier, and improve neurological deficits. However, the TNF signaling pathway activation could reverse these beneficial effects. In summary, our research suggests that by restoring the balance of gut microbiota, the levels of Ghrelin can be elevated, leading to the blockade of intracerebral TNF signaling pathway and enhanced GLP-1 expression, thereby mitigating post-TBI blood-brain barrier disruption and neurological injuries., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Bevacizumab is a commonly used anticancer drug in clinical practice, but it often leads to adverse reactions such as vascular endothelial damage, hypertension, arterial and venous thrombosis, and bleeding. This study investigated the protective effects of metformin against bevacizumab-induced vascular injury in a mouse model and examined the possible involvement of GDF15/PI3K/AKT/FOXO/PPARγ signaling in the effects., Materials and Methods: C57 male mice were purchased. To investigate metformin, the mice were assigned to the saline, bevacizumab (15 mg every 3 days), metformin (1200 mg/day), and bevacizumab+metformin groups. To investigate GDF15, the mice were assigned to the siNC+bevacizumab, siNC+bevacizumab+metformin, siGDF15+bevacizumab, and siGDF15+bevacizumab+metformin groups. Histological staining was used to evaluate vascular injury. Flow cytometry was used to evaluate apoptosis. ELISA was used to measure plasma endothelial injury markers and proinflammatory cytokines. qRT-PCR and western blot were used to determine the expression of GDF15 and PI3K/AKT/FOXO/PPARγ in aortic tissues., Results: Metformin alleviated bevacizumab-induced abdominal aortic injury, endothelial cell apoptosis, and systemic inflammation in mice (all P< 0.05). Metformin up-regulated GDF15 expression and PI3K/AKT/FOXO/PPARγ signaling in the abdominal aorta of mice treated with bevacizumab (all P< 0.05). siGDF15 abolished the vascular protective and anti-inflammatory effects of metformin (all P< 0.05). siGDF15 suppressed PI3K/AKT/FOXO/PPARγ signaling in the abdominal aorta of mice treated with bevacizumab (all P< 0.05)., Conclusion: Metformin attenuates bevacizumab-induced vascular endothelial injury, apoptosis, and systemic inflammation by activating GDF15/PI3K/AKT/FOXO/PPARγ signaling., 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.

Glioblastoma is the most common and aggressive form of primary brain cancer and the lack of viable treatment options has created an urgency to develop novel treatments. Personalized or predictive medicine is still in its infancy stage at present. This research aimed to discover biomarkers to inform disease progression and to develop personalized prophylactic and therapeutic strategies by combining state-of-the-art technologies such as single-cell RNA sequencing, systems pharmacology, and a polypharmacological approach. As predicted in the pyroptosis-related gene (PRG) transcription factor (TF) microRNA (miRNA) regulatory network, TP53 was the hub gene in the pyroptosis process in glioblastoma (GBM). A LASSO Cox regression model of pyroptosis-related genes was built to accurately and conveniently predict the one-, two-, and three-year overall survival rates of GBM patients. The top-scoring five natural compounds were parthenolide, rutin, baeomycesic acid, luteolin, and kaempferol, which have NFKB inhibition, antioxidant, lipoxygenase inhibition, glucosidase inhibition, and estrogen receptor agonism properties, respectively. In contrast, the analysis of the cell-type-specific differential expression-related targets of natural compounds showed that the top five subtype cells targeted by natural compounds were endothelial cells, microglia/macrophages, oligodendrocytes, dendritic cells, and neutrophil cells. The current approach-using the pharmacogenomic analysis of combined therapies-serves as a model for novel personalized therapeutic strategies for GBM treatment.

Myocardial ischemia/reperfusion (I/R) elicits an acute inflammatory response involving complement factors. Recently, we reported that myocardial necrosis was decreased in complement C3 -/- mice after heart I/R. The current study used the same heart model to test the effect of C3 on myocardial apoptosis and investigated if C3 regulation of apoptosis occurred in human cardiomyocytes. Comparative proteomics analyses found that cytochrome c was present in the myocardial C3 complex of WT mice following I/R. Incubation of exogenous human C3 reduced apoptosis in a cell culture system of human cardiomyocytes that did not inherently express C3. In addition, human C3 inhibited the intrinsic apoptosis pathway in a cell-free apoptosis system. Finally, human pro-C3 was found to bind with an apoptotic factor, pro-caspase 3, in a cell-free system. Thus, we present firsthand evidence showing that C3 readily reduces myocardial apoptosis via interaction with the intrinsic apoptotic pathway.

Background: Osteoprotegerin (OPG) is a secretory glycoprotein and participates in the progression of atherosclerotic lesions. We aim to explore the relationship between OPG and the prognosis of coronary artery disease (CAD)., Methods: Plasma OPG concentrations were measured in 3,766 patients with stable CAD enrolled in the PEACE trial. The PEACE trial (NCT00000558) group followed up the patients and examined their future clinical outcomes., Results: In summary, 208 (5.5%) primary outcomes occurred, 295 patients (7.8%) died from all-cause death, 128 (3.4%) died from cardiovascular causes, and 94 (2.5%) experienced heart failure during a median follow-up of 1,892 days. In addition, we found that higher plasma levels of OPG were associated with a higher incidence of all-cause death, cardiovascular death, and heart failure, even after adjusting clinical cofounders., Conclusion: It was demonstrated that elevated plasma OPG levels were associated with an increased incidence of all-cause death, cardiovascular death, and heart failure in patients with stable CAD., Systematic Review Registration: https://clinicaltrials.gov/ct2/show/NCT00000558?term=NCT00000558&draw=2&rank=1, identifier: NCT00000558., 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. The handling editor SB declared a past co-authorship with the author MT., (© 2023 Ma, Zhao, Yan, Liu, Zang, Zhang, Ruan, Xu and He.)

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have therapeutic potential in various diseases due to their capacity to transfer bioactive cargoes such as microRNAs (miRNAs or miRs) to recipient cells. The present study isolated EVs from rat MSCs and aimed to delineate their functions and molecular mechanisms in early brain injury following subarachnoid hemorrhage (SAH). We initially determined the expression of miR-18a-5p and ENC1 in hypoxia/reoxygenation (H/R)-induced brain cortical neurons and rat models of SAH induced by the endovascular perforation method. Accordingly, increased ENC1 and decreased miR-18a-5p were detected in H/R-induced brain cortical neurons and SAH rats. After MSC-EVs were co-cultured with cortical neurons, the effects of miR-18a-5p on neuron damage, inflammatory response, endoplasmic reticulum (ER) stress, and oxidative stress markers were evaluated based on ectopic expression and depletion experiments. miR-18a-5p overexpression in brain cortical neurons co-cultured with MSC-EVs was shown to impede neuron apoptosis, ER stress and oxidative stress while augmenting neuron viability. Mechanistically, miR-18a-5p bound to the 3'UTR of ENC1 and reduced its expression, weakening the interaction between ENC1 and p62. Through this mechanism, transfer of miR-18a-5p by MSC-EVs contributed to the eventual inhibition of early brain injury and neurological impairment following SAH. Overall, miR-18a-5p/ENC1/p62 may be a possible mechanism underlying the cerebral protective effects of MSC-EVs against early brain injury following SAH., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Accumulating evidence of the critical role of Ferrostatin-1 (Fer-1, ferroptosis inhibitor) in cerebral ischemia has intrigued us to explore the molecular mechanistic actions of Fer-1 delivery by bone marrow mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) in cerebral ischemia-reperfusion (I/R) injury. In vivo middle cerebral artery occlusion (MCAO) in mice and in vitro oxygen-glucose deprivation/reperfusion (OGD/R) in hippocampal neurons were developed to simulate cerebral I/R injury. After Fer-1 was confirmed to be successfully delivered by MSCs-EVs to neurons, we found that MSCs-EVs loaded with Fer-1 (MSCs-EVs/Fer-1) reduced neuron apoptosis and enhanced viability, along with curtailed inflammation and ferroptosis. The regulation of Fer-1 on GPX4/COX2 axis was predicted by bioinformatics study and validated by functional experiments. The in vivo experiments further confirmed that MSCs-EVs/Fer-1 ameliorated cerebral I/R injury in mice. Furthermore, poor expression of GPX4 and high expression of COX-2 were witnessed in cerebral I/R injury models. MSCs-EVs/Fer-1 exerted its protective effects against cerebral I/R injury by upregulating GPX4 expression and inhibiting COX-2 expression. Taken together, our study indicates that MSCs-EVs/Fer-1 may be an attractive therapeutic target for the treatment of cerebral I/R injury due to its anti-ferroptotic properties., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Coronary heart disease leading to myocardial ischemia is a major cause of heart failure. A hallmark of heart failure is myocardial fibrosis. Using a murine model of myocardial ischemia/reperfusion injury (IRI), we showed that, following IRI, in mice genetically deficient in the central factor of complement system, C3, myocardial necrosis was reduced compared with WT mice. Four weeks after the ischemic period, the C3 -/- mice had significantly less cardiac fibrosis and better cardiac function than the WT controls. Overall, our results suggest that innate immune response through complement C3 plays an important role in necrotic cell death, which contributes to the cardiac fibrosis that underlies post-infarction heart failure., Competing Interests: No conflict of interest for all., (© 2023 The Authors.)

Background: To describe grayscale ultrasound (US) features of metastatic ovarian tumors (MOTs) based on origin of the primary tumor in a large sample size study., Methods: This retrospective cross-sectional single-center study included 112 patients with 190 histopathologically confirmed MOTs. Among the patients, 102 collectively had 144 masses, which were detected via US. The clinical data and static US images of MOTs were collected., Results: The MOTs were mostly bilateral (78.9%) but had a lower rate of bilaterality when detected by US (55.6%). Breast cancer metastasis had the highest nondetection rate (69.6%), because its focal metastasis could only be recognized using histology or immunohistochemistry. The stomach was the most common origin of metastasis (45.3% and 50.7% detected via pathology and US, respectively). The US images were classified into three subtypes: multilocular solid (Type A), purely solid (Type B), and solid with several round or oval cysts (Type C). The MOTs that originated from the colon mostly belonged to Type A (65.1%) and closely mimicked primary epithelial ovarian tumor morphologically. The MOTs that originated from the stomach predominantly belonged to Types B (31.5%) and C (57.5%). Signet-ring cell carcinoma (SRCC) corresponded to Types B and C regardless of origin., Conclusions: The developed novel typing method provides more vivid images for classifying MOTs compared with existing typing methods. Given that no specific sonographic parameters have been established to distinguish MOTs from primary invasive ovarian tumors, these images may be helpful in diagnosing these masses., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-1149/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Alzheimer's disease (AD) accounts for approximately 60% of dementia cases worldwide. Advanced age is the most significant risk factor for AD and approximately two-thirds of cases relate to women. While the previous meta-analysis suggests that estrogen receptor (ESR) genetic polymorphisms are closely associated with dementia, the implications of this observation on a molecular level are not entirely understood. Our study explores this intricate molecular puzzle through the use of a variety of bioinformatics tools. Initially, we attempted to elucidate mechanisms underlying breast cancer development by identifying the high-throughput dataset of ESR1 -knockdown breast cancer tissue samples. Surprisingly, KEGG pathway enrichment showed that the most frequently occurring proteins were related to axonal guidance and inflammation-related gene markers. These observations were supported by an external high throughput dataset of AD inflammatory samples in vivo . Our results suggest that ESR1 is modulated by apolipoprotein E ( APOE ) through CEBPB/ATF4 , mir-155-5p, or mir-1-3p. Moreover, sea hare-hydrolysates (SHH), as one of the axonal guidance molecules, could regulate the STAT3/PRDM1/CEBPB pathway and consequently induce cell death through pyroptosis signaling pathways, trigger the secretion of IL1β, leading to neuroinflammation and worsening AD pathogenesis. Molecular docking verification demonstrated that the predicted natural products scoulerine and genistein displayed strong binding affinities for BACE1 and ESR1, respectively. This strategy can be used to design novel, personalized therapeutic approaches to treatment and a first-in-class clinical lead for the personalised treatment of AD.

Background: CLDN encodes a member of the claudin family. Claudin is a tight junction protein that is mainly involved in cell migration. Claudin family is of interest as a potential therapeutic target. Claudin18.2 is one of its important isoforms and is mainly expressed in the stomach. Its expression and prognosis in lung adenocarcinoma remain unknown. The aim of this study was to investigate the correlation between CLDN18 and claudin18.2 expression and prognosis in lung adenocarcinoma., Methods: Two cohorts were introduced in this study: one from The Cancer Genome Atlas (TCGA) CLDN18 mRNA public data (TCGA-LUAD, N = 551); the other from 1079 cases of lung adenocarcinoma diagnosed at the Fourth Hospital of Hebei Medical University, China, with immunohistochemical (IHC) detection of claudin18.2 in tissue microarrays. the IHC-positive cases were again verified by fluorescence in situ hybridization (FISH)., Results: The mRNA expression of CLDN18 was significantly lower in lung adenocarcinoma tissues than in normal lung tissues (P < 0.05). Among 1079 Chinese lung adenocarcinoma cases, the overall positive rate of IHC for Claudin18.2 was 7.78% (84/1079). Among those positive for IHC, the positive rate of FISH was 11.9% (10/84), which accounted for 0.9% of the total number of cases (10/1079). To explore the best scoring scheme for Claudin 18.2, we used a four-group (IHC4) and two-group (IHC2) scoring method for evaluation. We found that IHC4 better explained Claudin 18.2 expression and helped us to find specific differences in clinical factors for weak, moderate and strong Claudin 18.2 expression. This difference was not discernible in the IHC2 score. By survival analysis, we found that Claudin 18.2 (IHC4) was able to stratify the prognosis of lung adenocarcinoma patients, with strongly positive patients having a better prognosis than the other subgroups (p < 0.05). We also found that patients with EGFR wild type or PD-L1 < 1% accompanied by strong positive claudin18.2 had a significantly better prognosis than other subgroups (P < 0.05)., Conclusion: Claudin18.2 (IHC4) better reveals the clinical and prognostic characteristics of patients with lung adenocarcinoma. Patients with EGFR wild type and PD-L1 < 1% have a better prognosis and partially overlap with claudin18.2 expression, so claudin18.2 may also be an important biomarker for lung adenocarcinoma testing, which is particularly important for EGFR wild type and PD-L1 < 1%., Competing Interests: Conflict of Interest This manuscript entitled " Expression and prognostic analysis of CLDN18 and Claudin18.2 in lung adenocarcinoma" describes original work that has not been considered for publication in any other journal. All authors approved the manuscript and the submission of this report. There are no conflicts of interest., (Copyright © 2022. Published by Elsevier GmbH.)

Peach (Prunus persica [L.] Batsch) as an economically important fruit tree is widely cultivated in Shenzhou, China. In September 2021, peach rust was observed in the peach tree in Shenzhou City, Hebei Province (lat. 38°02'56'' N, long. 115°54'57'' E, altitude 22 m). We investigated a peach orchard with a planting area of 1334 m2, where a total of 162 peach trees were planted, and found that about 10% of peach trees exhibited severe disease symptoms. The leaves of infected plant developed 100% disease symptoms, in which 50% of the infected leaves showed about 10 small pale-yellow spots on the front of leaves and reddish-brown pustules on the corresponding abaxial surface of leaves. Urediniospores varied from obovoid to clavate in shape, sometimes in irregular shape. They were orange-brown, echinulate near base with spines smaller towards apex and often smooth at apex, with germ pores 3-4 at equator, size ranging from 25.4 to 38.6 × 10.1 to 18.7 µm (n=100), and with wall 1 to 1.5μm thick at sides and 5-7 μm thick at apex. Golden capitate paraphyses were present, ranging from 25 to 40 µm in length, with a head in diameter of 12 to 14 µm and a tail in width of 5.2 to 6.5 µm. Based on the rust morphological characters, this pathogen was primarily identified as Tranzschelia discolor (Fuckel) Tranzschel & Litv. (Hiratsuka et al. 1992). For molecular identification, total DNA was extracted from 2 isolates, respectively, and the internal transcribed spacer (ITS) region was PCR-amplified using the primer set ITS5-u and ITS4-u (Pfunder et al. 2001). Obtained sequences were compared with sequences in the GenBank repository using BLAST algorithm. BLAST showed a 100% sequence identify to T. discolor (accession nos. AB097449、MT786217、KU712078、KY764179、MH599069). The sequence has been deposited in GenBank with (accession NO. ON950745 and ON950747). Thus, combining morphological observations and molecular identification, the isolate was identified as T. discolor. The pathogenicity was verified by inoculating the abaxial surface of peach leaves with a suspension of 1 × 106 urediniospores/ml. Peach leaves sprayed with sterile water were used as controls. The inoculated peach trees were placed in a greenhouse at 20°C under dark for 24 hours and maintained at 100% relative humidity to promote disease development. Next, the peach trees were grown in a greenhouse at 20°C with a 12 h day length and symptoms were observed on the leaves 14 days after inoculation. In contrast, the control leaves were asymptomatic. Previous studies reported that peach rust occurred in Oman, Korea and Brazil was caused by T. discolor. (Deadman M L, et al.2007, Shin, H D, et al. 2019, Vidal G S, et al. 2021). To our knowledge, this is the first report of T. discolor as a causal agent causing peach leaf rust in Northern China, which will enable us to rapidly diagnose this disease, identify the occurrence of this disease and develop adequate management strategies to control it in China.

A total of 14 Festuca sinensis seed lots were collected from different geographical locations on the Qinghai-Tibet Plateau to study the seed microbiota and determine the abiotic (temperature, precipitation, and elevation) and biotic ( Epichloë sinensis infection rate) factors likely to shape the seed microbiome. The 14 seed lots had different bacterial and fungal structures and significantly different diversities ( p < 0.05). The α-diversity indices of the bacteria were significantly correlated with precipitation ( p < 0.05), whereas those of the fungi were significantly correlated with temperature ( p < 0.05). Microbiota analysis showed that Proteobacteria, Cyanobacteria, and Bacteroidetes were the most abundant bacteria at the phylum level in the seeds, and Ascomycota and Basidiomycota were the most abundant fungi. β-diversity analysis suggested large differences in the microbial communities of each sample. Redundancy analysis showed that temperature and precipitation were the main environmental factors that drive variations in the microbial community, at the medium-high elevation (3,000-4,500 m), the impact of temperature and precipitation on microbial community is different, and the other elevations that effect on microbial community were basically identical. Spearman's correlation analysis showed that the relative abundances of the most abundant bacterial phyla were significantly correlated with temperature ( p < 0.05), whereas those of the most abundant fungal phyla were significantly correlated with precipitation ( p < 0.05). E. sinensis infection rates were significantly correlated with elevation and temperature ( p < 0.05). These results suggest that temperature and precipitation are the key factors driving the microbial community, that temperature and elevation also had a great influence on the E. sinensis infection rate, and that environmental factors (temperature and elevation) may further affect the microbial community by regulating the E. sinensis infection rate., 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 © 2022 Gao, Chen, Luo, Liu, Tian, Nan and Zhou.)

Used in Asian countries, including China, Japan, and Thailand, Houttuynia cordata Thumb ( H. cordata ; Saururaceae, HC) is a traditional herbal medicine that possesses favorable antiviral properties. As a potent folk therapy used to treat pulmonary infections, further research is required to fully elucidate the mechanisms of its pharmacological activities and explore its therapeutic potential for treating pneumonia caused by SARS-CoV-2. This study explores the pharmacological mechanism of HC on pneumonia using a network pharmacological approach combined with reprocessing expression profiling by high-throughput sequencing to demonstrate the therapeutic mechanisms of HC for treating pneumonia at a systemic level. The integration of these analyses suggested that target factors are involved in four signaling pathways, including PI3K-Akt, Jak-STAT, MAPK, and NF-kB. Molecular docking and molecular dynamics simulation were applied to verify these results, indicating a stable combination between four metabolites (Afzelin, Apigenin, Kaempferol, Quercetin) and six targets (DPP4, ELANE, HSP90AA1, IL6, MAPK1, SERPINE1). These natural metabolites have also been reported to bind with ACE2 and 3CLpro of SARS-CoV-2, respectively. The data suggest that HC exerts collective therapeutic effects against pneumonia caused by SARS-CoV-2 and provides a theoretical basis for further study of the active drug-like ingredients and mechanism of HC in treating pneumonia.

Glucose metabolism regulates cell growth and affects astaxanthin accumulation in the green algae Chromochloris zofingiensis . Hub gene functioning in this bioactive compound has been illustrated at the genome, transcriptome and metabolome level, but is rather limited from a proteome aspect. Microalgal cell produce an enhanced biomass (8-fold higher) but decreased lipid and astaxanthin content (~20% less) in the glucose condition compared to the control. Here, we investigate the proteomic response of C. zofingiensis grown with and without glucose using an LC-MS/MS-based Tandem Mass Tag (TMT) approach. The proteomic analysis demonstrated that glucose supplementation triggers the upregulation of 105 proteins and downregulation of 151 proteins. Thus, the carbon and energy flux might flow to cell growth, which increased the associated protein abundance, including DNA polymerase, translation initiation factor, 26S proteasome regulatory subunits, and the marker enzyme of the TCA cycle ribosomal protein. Moreover, the glucose supplement triggered the downregulation of proteins mainly involved in photosynthesis, chloroplasts, valine, leucine and isoleucine biosynthesis, 2-oxocarboxylic acid metabolism, and pantothenate and CoA biosynthesis pathways. This proteomic analysis is likely to provide new insights into algal growth and lipid or astaxanthin accumulation upon glucose supplementation, providing a foundation for further development of C. zofingiensis as oleaginous microalga for bioengineering applications.

Background: Acute ST-segment elevation myocardial infarction (STEMI) is a serious multiple acute cardiovascular disease. This study investigated the effect of statins on the efficacy and prognosis of STEMI patients after emergency PCI., Methods: From October 2019 to January 2021, 98 patients with STEMI in our hospital were selected and divided into study group and control group. The study group took atorvastatin 40 mg 2 hours before surgery, 40 mg/day after surgery, and 20 mg/day 1 week later. The control group received 20 mg of atorvastatin every night after admission. The cardiac output, left ventricular ejection fraction, blood flow classification, vagus nerve function, heart rate deceleration force and chemoreflex sensitivity were compared between the two groups, and recorded the incidence of adverse reactions before and after treatment and 3 months after treatment. The number of major adverse cardiac events (MACEs) was also recorded., Results: Before treatment, there were no differences in CO, CI, and LVEF between the study and control groups. After treatment, CO, CI, and LVEF in the study group were significantly higher than those in the control group. Before treatment, there was no significant difference in TIMI blood flow classification among the groups, and after treatment, the study group was better than the control group. DC and ChRS were significantly higher in the study group than in the control group. There was no difference in the incidence of adverse reactions between the study group and the control group. However, the incidence of MACE in the study group was lower than that in the control group., Conclusion: Enhanced-dose atorvastatin for STEMI patients improved PCI treatment effect, cardiac function, and vagus nerve function and reduced the incidence of adverse cardiac events. Thus, statins are safe and worth considering., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Wenzhong Chen et al.)

Objective: To explore the potential and mechanism of action of poricoic acid A (PAA) in treatment of cardiorenal injury and fibrosis due to cardiorenal syndrome (CRS)., Materials and Methods: A CRS rat model was established by transabdominal subtotal nephrectomy (STNx). The experimental group was treated by gavage of PAA (10 mg/kg/day). After 8 weeks of treatment, echocardiography was utilized for detecting heart-related indexes in rats. HE and Masson staining were conducted to detect the degree of pathological damage and fibrosis in rat kidney tissue, respectively. In addition, serum blood urea nitrogen (BUN), serum creatinine (SCr), and 24-hour urine protein were measured biochemically. Also, the levels of inflammatory factors (IL-1 β , IL-6, and IL-10) in rat kidneys were measured using ELISA. Western blot was used to examine the expression of NF- κ B/MAPK pathway-related proteins., Results: In this study, a CRS rat model was successfully established by STNx surgery. PAA treatment could significantly alleviate the damage of heart and kidney function in CRS rats and reduce the pathological damage of kidney tissue and renal fibrosis. Meanwhile, PAA could also inhibit the renal inflammatory response through downregulating IL-1 β and IL-6 levels in the kidney tissue and upregulating IL-10 level. Further mechanism exploration showed that the NF- κ B/MAPK signaling pathway was significantly activated in CRS rats, while PAA treatment could markedly inhibit the NF- κ B/MAPK signaling pathway activity in CRS rats., Conclusion: PAA can obviously improve the pathological damage and fibrosis of renal tissue in CRS rats and maintain the function of the heart and kidney. The above functions of PAA may be achieved by inhibiting the NF- κ B/MAPK signaling pathway activity. Briefly speaking, PAA can serve as a potential drug for CRS treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Wenzhong Chen et al.)

Background: Whether to preserve the uterine round ligament during laparoscopic inguinal hernia repair in women is controversial. In this study, we aimed to compare outcomes of uterine round ligament preservation versus transection during such surgery and to explore the impact and long-term outcomes of transecting the round ligament., Methods: The study cohort comprised 419 women who had undergone laparoscopic inguinal hernia repair in Beijing Chaoyang Hospital and Qilu Hospital from January 2013 to January 2020; 393 (93.8%) of whom were successfully followed up. Patient characteristics and technical details of the operative procedure were collected and analyzed retrospectively. Early and late postoperative follow-up data, complications, especially symptoms related to retroflexed uterus, and fertility outcomes, were collected by a single follow-up nurse who was blinded to the operative procedure., Results: There were 218 women (239 sides) in the uterine round ligament preservation group and 175 (182 sides) in the transection group. The patients in the preservation group were younger (45.9 vs. 53.6 years, p = 0.000), and had lower American Society of Anesthesiologists scores (p = 0.000). The median follow-up times in the preservation and transection groups were 41.8 ± 24.2 and 42.7 ± 24.6 months, respectively (p = 0.692). Compared with the transection group, the preservation group had longer operative times for repair of both primary and recurrent hernias. Intraoperative bleeding, length of hospital stay, development of seromas, recurrence rate, incidence of postoperative pain at the first and third postoperative months, and time of last outpatient visit were similar in the two groups. There were more premenopausal patients in the preservation group; however, we found no evidence that transection of the round ligament affected subsequent pregnancy or childbirth. Moreover, we identified no differences in dyspareunia, dysmenorrhea, chronic pelvic pain, or uterine prolapse., Conclusion: Transection of the round ligament during laparoscopic inguinal hernia repair in women does not increase the incidence of dyspareunia, dysmenorrhea, chronic pelvic pain, or uterine prolapse, whereas it has the advantage of reducing the operation time., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Long noncoding RNAs (LncRNAs) possess crucial roles in carcinogenesis. The current study aims to evaluate the effects of interleukin-1β (IL-1β)-mediated lncRNA cardiac hypertrophy-related factor (CHRF)/microRNA-489 (miR-489)/myeloid differentiation factor 88 (Myd88) on non-small-cell lung cancer (NSCLC). Methods: Initially, the expression of IL-1β and lncRNA CHRF in NSCLC cells and tissues was determined, respectively. H460 cell line with highest lncRNA CHRF expression was selected for in vitro experimentations. Afterward, the interaction among lncRNA CHRF, miR-489, and Myd88 was verified with their significance in cell functions and tumorigenicity and lung metastasis analyzed following. Results: IL-1β and lncRNA CHRF was remarkably upregulated in NSCLC. IL-1β was able to elevate lncRNA CHRF expression. Additionally, lncRNA CHRF targeted miR-489 and miR-489 targeted Myd88. Moreover, functional assay results suggested that under IL-1β treatment, lncRNA CHRF induced NSCLC cell malignant properties and tumorigenicity and lung metastasis through modulation of miR-489/Myd88 axis. Conclusion: Taken together, our findings revealed that IL-1β-induced elevation of lncRNA CHRF aggravated NSCLC through modulation of miR-489/Myd88 axis, which provides a novel direction for NSCLC therapy development., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: The 5-year survival rate of patients with esophageal squamous cell cancer (ESCC) is very low. However, long-term aspirin use has been suggested to have an adjuvant therapeutic effect. We therefore investigated the effect of long-term aspirin use before ESCC diagnosis on postoperative patient survival., Methods: We carried out a retrospective cohort study of patients who underwent esophageal cancer resection in our hospital from 2008 to 2018. Patients were divided into an aspirin group (n = 79) and control group (n = 79), and were followed up until December 2019. We analyzed the clinicopathological and follow-up data of the patients during hospitalization, and the cyclooxygenase-2 (COX-2) protein expression levels by immunohistochemistry, and related these to postoperative survival., Results: Patients who took aspirin had significantly lower survival rates than those who did not. COX-2-negative patients had better survival than patients with either low or high COX-2 expression levels. T stage was the only independent predictor of survival in patients who took aspirin., Conclusions: Long-term regular use of aspirin before diagnosis had an adverse effect on postoperative survival in patients with ESCC. Different COX-2 protein expression levels were associated with significantly different postoperative survival rates, with COX-2-positive patients having the poorest survival.

Background: Hypotension post percutaneous coronary intervention (PCI) causes stent thrombosis and reduced coronary perfusion, which aggravate myocardial ischemia and lead to patient death. Therefore, the accuracy and timeliness of blood pressure monitoring (BPM) are crucial for the nursing of patients post PCI. However, it is still controversial whether invasive blood pressure monitoring (IBPM) or non-invasive blood pressure monitoring (NIBPM) should be used for patients post PCI, and the magnitude of their assistance for patients' recovery remains unclear., Methods: A randomized controlled trial was performed in this study. 126 ST-segment elevation myocardial infarction (STEMI) patients post PCI were recruited and randomly divided into two groups (NIBPM group n = 63; IBPM group n = 63)., Results: Clinical characteristics and physiological outcomes of participants received different BPM methods were collected and analyzed to compare the effects of these two methods on the nursing of PCI patients. Compared to NIBPM group, IBPM assisted to shorten the time of myocardial ischemia, promote coronary reperfusion, reduce the occurrence of cardiovascular disease and other complications, and ultimately reduce the mortality of patients post PCI., Conclusion: The application of IBPM contributed to reduce the occurrence of complications, shorten the time of vascular reperfusion, and guide treatment of clinicians in time., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Microalgal cells serve as solar-powered factories that produce pharmaceuticals, recombinant proteins (vaccines and drugs), and valuable natural byproducts that possess medicinal properties. The main advantages of microalgae as cell factories can be summarized as follows: they are fueled by photosynthesis, are carbon dioxide-neutral, have rapid growth rates, are robust, have low-cost cultivation, are easily scalable, pose no risk of human pathogenic contamination, and their valuable natural byproducts can be further processed. Despite their potential, there are many technical hurdles that need to be overcome before the commercial production of microalgal pharmaceuticals, and extensive studies regarding their impact on human health must still be conducted and the results evaluated. Clearly, much work remains to be done before microalgae can be used in the large-scale commercial production of pharmaceuticals. This review focuses on recent advancements in microalgal biotechnology and its future perspectives.

Background: In order to reduce the risk of invasive blood pressure monitoring and improve the safety and efficiency, this article mainly analyzes the effectiveness and safety of using positive-pressure connector for invasive blood pressure monitoring in patients with coronary artery interventional therapy, so as to improve the invasive blood pressure monitoring method. Aim: To study and analyze the application of positive-pressure connector in invasive blood pressure monitoring in coronary interventional therapy. Methods: From October 2017 to October 2019, a total of 120 patients admitted to Cangzhou Central Hospital, Cangzhou, Hebei, China, for coronary interventional therapy with invasive blood pressure monitoring were selected and divided into a control group and an experimental group by drawing lots with 60 patients in each group. Positive-pressure connector was used for invasive blood pressure detection in the experimental group, and heparin cap connector was used for invasive blood pressure detection in the control group. The effectiveness and safety of blood pressure monitoring in the two groups were compared, and the influence of different joints on invasive blood pressure monitoring was analyzed. Results: The influencing factors of puncture efficiency in the experimental group (6.67%) were significantly lower than those in the control group (30.00%) ( P < 0.05). There was no significant difference in catheter bending between the experimental group and the control group ( P > 0.05). The experimental group exhibited a remarkably higher puncture safety rate (93%) compared to the control group (67%) ( P < 0.05). There was no significant difference in arterial blood pressure between the two groups with different indwelling time ( P > 0.05). The frequency of extubation and reinsertion in the experimental group was significantly lower than that in the control group ( P < 0.05). Factors influencing puncture safety in the experimental group were significantly lower than those in the control group ( P < 0.05). Conclusion: The use of positive-pressure connector for invasive blood pressure monitoring in patients with coronary artery interventional therapy can greatly improve the safety of blood pressure monitoring and reduce the suffering of patients. Therefore, the application of positive-pressure connector in invasive blood pressure monitoring is worthy of promotion and application in clinical practice., 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 © 2021 Wang, Liu, Peng, Jiang, Guo and Xu.)

Certain nanomaterials can filter and alter unwanted compounds due to a high surface area, surface reactivity, and microporous structure. Herein, γ-Bi 2 MoO 6 particles are synthesized via a colloidal hydrothermal approach using organically modified Laponite as a template. This organically modified Laponite interlayer serves as a template promoting the growth of the bismuth molybdate crystals in the [010] direction to result in hybrid Laponite-Bi 2 MoO 6 particles terminating predominantly in the {100} crystal facets. This resulted in an increase in particle size from lateral dimensions of <100 nm to micron scale and superior adsorption capacity compared to bismuth molybdate nanoparticles. These {100}-facet terminated particles can load both cationic and anionic dyes on their surfaces near-spontaneously and retain the photocatalytic properties of Bi 2 MoO 6 . Furthermore, dye-laden hybrid particles quickly sediment, rendering the task of particle recovery trivial. The adsorption of dyes is completed within minutes, and near-complete photocatalytic degradation of the adsorbed dye in visible light allowed recycling of these particles for multiple cycles of water decontamination. Their adsorption capacity, facile synthesis, good recycling performance, and increased product yield compared to pure bismuth molybdate make them promising materials for environmental remediation. Furthermore, this synthetic approach could be exploited for facet engineering in other Aurivillius-type perovskites and potentially other materials.

Designing nanostructures with extended light absorption via defect engineering is a useful approach for the synthesis of efficient photocatalysts. Herein, ZnIn 2 S 4 was grown hydrothermally in the modified interlayer space of Laponite, resulting in lamellae consisting of Zn-defective ZnIn 2 S 4 several unit cells thick. In the process it was found that Mg 2+ leached from Laponite during synthesis led to the formation of Zn defects in ZnIn 2 S 4 . This resulted in nanohybrids with light absorption extended across the visible spectrum and in improved charge transfer due to the layered structure formed via confined growth. Compared with pure ZnIn 2 S 4 , Zn-defective ZnIn 2 S 4 -Laponite hybrids have increased photocurrent generation and photocatalytic performance. The leaching of Mg 2+ and the resulting formation of Zn defects was attenuated by addition of 4 mM Mg 2+ to the reaction, due to a combination of shifting of the equilibrium of Mg 2+ leaching toward stability, and increased ionic strength. In summary, this work demonstrates the growth of ∼1 nm thick lamellae of ZnIn 2 S 4 , presents a unique strategy to generate cation defects in nanomaterials and the mechanism behind it, and also provides an approach to mitigate Mg 2+ leaching in such syntheses.

There has been a recent drive to develop non-fluorinated superhydrophobic coatings due to the toxicity, cost, and environmental impact of perfluorinated components. One of the main challenges in developing superhydrophobic coatings in general and non-fluorinated superhydrophobic coatings in particular is optimization of mechanical durability, as the rough asperities required for maintaining superhydrophobicity tend to be easily removed by abrasion. Although rough and self-similar hydrophobic surfaces composed of loosely adhered particles or highly porous structures tend to produce excellent superhydrophobicity, they have low inherent mechanical durability and their longevity under real conditions is compromised. To address this issue, this work investigates the addition of a polymeric matrix material (the binder) to hydrophobic nanoparticles (the filler) to produce spray-coated superhydrophobic surfaces with improved inherent mechanical durability. Hansen solubility parameters were used to tune the interactions between the binder, filler, and solvent used to deliver the coating. It was found that lowering the binder/filler miscibility and using a poor solvent mixture generates more surface roughness, thereby lowering the minimum filler load required to achieve superhydrophobicity. This leads to an overall more inherently durable system that remains hydrophobic for thousands of light abrasion cycles.

Extracellular vesicles (EVs) are capable of transferring microRNAs (miRNAs or miRs) between two different types of cells and also serve as vehicles for delivery of therapeutic molecules. After peripheral nerve injury, abnormal expression patterns of miRNAs have been observed in dorsal root ganglia (DRG) sensory neurons. We hypothesized that sensory neurons secrete miRs-containing EVs to communicate with macrophages. We demonstrated that miR-23a was upregulated in DRG neurons in spared nerve injury (SNI) mouse models. We also found that miR-23a was enriched in EVs released by cultured DRG neurons following capsaicin treatment. miR-23a-containing EVs were taken up into macrophages in which increased intracellular miR-23a promoted pro-inflammatory phenotype. A20 was verified as a target gene of miR-23a. Moreover, intrathecal delivery of EVs-miR-23a antagomir attenuated neuropathic hypersensitivity and reduced the number of M1 macrophages in injured DRGs by targeting A20. In conclusion, these results demonstrate that sensory neurons transfer EVs-encapsulated miR-23a to activate M1 macrophages and enhance neuropathic pain following the peripheral nerve injury. The study highlighted a new therapeutic approach to alleviate chronic neuropathic pain after nerve trauma by targeting detrimental miRNA in sensory neurons.

Background: Cerebral ischemia-reperfusion (I/R) injury, the most common form of stroke, has high mortality and often brings persistent and serious brain dysfunction among survivors. Administration of adipose-derived mesenchymal stem cells (ASCs) has been suggested to alleviate the I/R brain injury, but the mechanism remains uncharacterized. Here, we aimed at investigating the mechanism of ASCs and their extracellular vesicles (EVs) in the repair of or protection from I/R injury., Methods: We established the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reperfusion (OGD/RP) neuron model. ASCs or ASC-derived EVs (ASC-EVs) were co-cultured with neurons. RT-qPCR and Western blot analyses determined microRNA (miRNA)-22-3p, BMP2, BMF, and KDM6B expression in neurons upon treatment with ASC-EVs. Bioinformatics analysis predicted the binding between miR-22-3p and KDM6B. Using gain- and loss-of-function methods, we tested the impact of these molecules on I/R injury in vivo and in vitro., Results: Treatment with ASCs and ASC-derived EVs significantly alleviated the I/R brain injury in vivo, elevated neuron viability in vitro, and decreased apoptosis. Interestingly, miR-22-3p was upregulated in ASC-EVs, and treatment with EV-miR-22-3p inhibitor led to increased apoptosis and decreased neuronal. Of note, miR-22-3p bound to and inhibited KDM6B, as demonstrated by dual-luciferase reporter gene assay and Western blot assay. Overexpression of KDM6B enhanced apoptosis of neurons in the OGD/RP model, and KDM6B bound to BMB2 and promoted its expression by binding to BMP2. Silencing of BMF reduced infarct volume and apoptosis in the stroke model., Conclusion: Results support a conclusion that ASC-EV-derived miR-22-3p could alleviate brain ischemic injury by inhibiting KDM6B-mediated effects on the BMP2/BMF axis. These findings compelling indicate a novel treatment strategy for cerebral ischemic injury.

Calcium dobesilate (CaD) is used effectively in patients with diabetic microvascular disorder, retinopathy, and nephropathy. Here we sought to determine whether it has an effect on cardiomyocytes calcium mishandling that is characteristic of diabetic cardiomyopathy. Cardiomyocytes were sterile isolated and cultured from 1 to 3 days neonatal rats and treated with vehicle (Control), 25 mM glucose+300 μM Palmitic acid (HG+PA), 100 μM CaD (CaD), or HG+PA+CaD to test the effects on calcium signaling (Ca 2+ sparks, transients, and SR loads) and reactive oxygen species (ROS) production by confocal imaging. Compared to Control, HG+PA treatment significantly reduced field stimulation-induced calcium transient amplitudes (2.22 ± 0.19 vs. 3.56 ± 0.21, p < 0.01) and the levels of caffeine-induced calcium transients (3.19 ± 0.14 vs. 3.72 ± 0.15, p < 0.01), however significantly increased spontaneous Ca 2+ sparks firing levels in single cardiomyocytes (spontaneous frequency 2.65 ± 0.23 vs. 1.72 ± 0.12, p < 0.01) and ROS production (67.12 ± 4.4 vs. 47.65 ± 2.12, p < 0.05), which suggest that HG+PA treatment increases the Spontaneity Ca 2+ spark frequency, and then induced partial reduction of SR Ca 2+ content and subsequently weaken systolic Ca 2+ transient in cardiomyocyte. Remarkably, these impairments in calcium signaling and ROS production were largely prevented by pre-treatment of the cells with CaD. Therefore, CaD may contribute to a good protective effect on patients with calcium mishandling and contractile dysfunction in cardiomyocytes associated with diabetic cardiomyopathy., 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 © 2021 Deng, Cai, Hao, Liu, Chen, Li, Liu, Liao, Fu, Chen, Qin and Yan.)

Background: Human Sapoviruses (SaVs) has been reported as one of the causative agents of acute gastroenteritis (AGE) worldwide. An outbreak of SaVs affected 482 primary school students during spring activities from February 24 to March 11, 2019 in Shenzhen City, China. Our study was aimed at determining the epidemiology of the outbreak, investigating its origins, and making a clear identification of the SaVs genetic diversity., Methods: Epidemiological investigation was conducted for this AGE outbreak. Stool samples were collected for laboratory tests of causative agents. Real-time reverse-transcription polymerase chain reaction (rRT-PCR) and conventional RT-PCR were used for detecting and genotyping of SaVs. The nearly complete genome of GII.8 SaV strains were amplified and sequenced by using several primer sets designed in this study. Phylogenetic analysis was performed to characterize the genome of GII.8 SaV strains., Results: The single factor analysis showed that the students who were less than 1.5 m away from the vomitus in classroom or playgroundwere susceptible (P < 0.05). Seven of 11 fecal samples from patients were positive for GII.8 SaV genotype. In this study, we obtained the genome sequence of a SaV GII.8 strain Hu/SaV/2019008Shenzhen/2019 /CHN (SZ08) and comprehensively analyzed the genetic diversity. The phylogenetic analysis showed that the GII.8 strain SZ08 formed an independent branch and became a novel variant of GII.8 genotype. Strain SZ08 harbored 11 specific amino acid variations compared with cluster A-D in full-length VP1., Conclusions: This study identified SaVs as the causative agents for the AGE outbreak. Strain Hu SZ08 was clustered as independent branch and there was no recombination occurred in this strain SZ08. Further, it might become the predominant strain in diarrhea cases in the near future. Constant surveillance is required to monitor the emerging variants which will improve our knowledge of the evolution of SaVs among humans.

Alfalfa (Medicago sativa L.) is an important forage legume in farming and animal husbandry systems. This study assessed the effects of arbuscular mycorrhizal fungi (AMF) and phosphate-solubilizing bacteria (PSB) on alfalfa growth under different phosphorus application levels. In this experiment, a complete randomized block design was used. The following four bacterial applications were used: inoculation of Funneliformis mosseae (Fm), inoculation of Bacillus megaterium (Bm), inoculation of mixed species (Fm × Bm) and noninoculation treatment (CK). Phosphorus (P) treatment was applied at the following four levels: 0 mg kg -1 (P 0 ), 50 mg kg -1 (P 1 ), 100 mg kg -1 (P 2 ) and 150 mg P kg -1 (P 3 ). The results showed that with the increase in phosphorus application, each index increased first and then decreased. The J 2 treatment was significantly greater than the J 0 treatment (P < 0.05) under the same bacterial treatment. In each cropping period the difference in each index to alfalfa was extremely significant under J, P treatment and J × P interactive treatment (P < 0.01). The indexes were compared by membership function. The priority order was as follows: J 3 P 2  > J 1 P 2  > J 3 P 1 treatment. Therefore, when phosphorus was applied at 100 mg kg -1 , the mixed inoculation of Fm × Bm was optimal, benefitting mycorrhiza growth and the production performance of alfalfa.

Human cancers often related to signal pathway variation, the phosphoinositide-3-kinase (PI3K) pathway is one of it. AKT kinase family is the most common downstream of PI3K pathway. The serum and glucocorticoid kinase 2(SGK2) is similar to AKT as the downstream of PI3K pathway. Up to now, we have few understanding of SGK2 in colon cancer. We determined the 20 colon cancer samples mRNA level. Later, we silence SGK2 in colon cancer cells. We found that SGK2 is up-regulated in colon cancer tissue/cells and have positive correlation with cell migration and invasive potential in human colon cancer cell line CACO2 and HCT116. The expression level of SGK2 have positive correlation with expression of mesenchymal marker N-cadherin and Vimentin and negative correlation with the expression of epithelial marker E-cadherin in CACO2 and HCT116 cells. In short, our research indicate that SGK2 is overexpressed in colon cancer and promotes EMT in colon cancer cells., Competing Interests: Declaration of competing interest All authors in this manuscript declare no conflict of interest., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Human epidermal growth factor receptor 2 (HER2) is composed of an extracellular domain (ECD), a lipophilic transmembrane region and an intracellular domain (ICD). The most commonly used method to determine the status of HER2 is immunohistochemistry. However, false‑negative results are sometimes given, which causes some patients to lose the opportunity for anti‑HER2 therapy. We found that calpain‑10 may prohibit HER2‑ECD into peripheral blood resulting in a HER2‑negative result by the immunohistochemical method. We enrolled 289 patients into our experiment to assess the relationship between sHER2‑ECD and calpain‑10. The results showed that there was a positive correlation between sHER2‑ECD and calpain‑10. Moreover, we also investigated the prognostic values of sHER2‑ECD and calpain‑10 in breast cancer patients. According to the follow‑up results, positive sHER2‑ECD and tissue calpain‑10 were indicative of a poor prognosis in breast cancer patients. Subsequently, we further validated the relationship between the two molecules in in vitro experiments. In the in vitro experiments, the level of HER2‑ECD in the culture medium was increased or decreased with a decrease or increase in calpain‑10 by transfection technology, showing an inverse association. The results indicated that sHER2‑ECD and tissue calpain‑10 levels were powerful factors to assess the status of HER2. In combination with tissue HER2 detection, the occurrence of false‑negative HER2 was reduced, providing patients with additional treatment opportunities. In conclusion, sHER2‑ECD and tissue calpain‑10 may be used as new prognostic indices for breast cancer.

Baicalin is an important flavonoid compound THAT is isolated from the Scutellaria baicalensis Georgi Chinese herb and plays a critical role in anti‑oxidative, anti‑inflammatory, anti‑infection and anti‑tumor functions. Although baicalin can suppress the proliferation of tumor cells, the underlying mechanisms of baicalin in bleomycin (BLM)‑induced pulmonary fibrosis remain to be elucidated. Thus, the aim of the present study was to determine the role of baicalin in pulmonary fibrosis and fibroblast proliferation in rats. Hematoxylin and eosin (H&E) and Masson staining were used to measure the morphology of pulmonary fibrosis, ELIASA kits were used to test the ROS and inflammation, and western blotting and TUNEL were performed to study the apoptosis proteins. In vitro, MTT assay, flow cytometry, western blotting and immunofluorescence were performed to investigate the effects of baicalin on proliferation of fibroblasts. The most significantly fibrotic changes were identified in the lungs of model rats at day 28. Baicalin (50 mg/kg) attenuated the degree of pulmonary fibrosis, and the hydroxyproline content of the lung tissues was decreased in the baicalin group, compared with the BLM group. Further investigation revealed that baicalin significantly increased glutathione peroxidase (GSH‑px), total‑superoxide dismutase (T‑SOD) and glutathione (GSH) levels, whilst decreasing that of serum malondialdehyde (MDA). TUNEL‑positive cells were significantly decreased in rats treated with baicalin group, compared with the model group. Furthermore, it was found that BLM promoted fibroblasts viability in a dose‑dependent manner in vivo, which was restricted following treatment with different concentrations of baicalin. Moreover, BLM promoted the expression levels of cyclin A, D and E, proliferating cell nuclear antigen, phosphorylated (p)‑AKT and p‑calcium/calmodulin‑dependent protein kinase type. BLM also promoted the transition of cells from the G0/G1 phase to the G2/M and S phases, and increased the intracellular Ca2+ concentration, which was subsequently suppressed by baicalin. Collectively, the results of the present study suggested that baicalin exerted a suppressive effect on BLM‑induced pulmonary fibrosis and fibroblast proliferation.

MoS 2 is a 2D semiconductor where exfoliation to a single layer results in improved catalytic properties. However, its high surface energy can lead to extensive aggregation, resulting in degraded catalytic performance and stability. Combined with a lack of dispersibility in water, this represents a pitfall for catalysis in the aqueous phase. Herein, we present the use of nanoscopic layered silicates pillared with a cationic surfactant to template the growth of MoS 2 in the interlayer space. This provides heterostructured layered nanoparticles ∼25 nm wide by 3-8 nm thick containing isolated MoS 2 layers. The resulting nanohybrids retain the disc-like morphology and surface chemistry of the clays, providing good aqueous stability, while also providing access to the catalytic edge-sites of the MoS 2 layer. In addition to significant enhancement of catalytic dye degradation, molecular aggregation on the highly charged clay interface is comparable to unmodified clays. These particles are ideal for studies of charge-transport properties in confined semiconductor layers, as well as hierarchical self-assembly into functional materials. This study paves the way to colloidal synthesis of nanoparticulate heterostructures with other functional layered materials, particularly where particle exfoliation, covalent modification, and aqueous stability are concerns.

Alfalfa ( Medicago sativa L.) is an important forage legume in arid areas, but limited water resources and low fertilizer utilization have restricted its agricultural development. Meanwhile, studies on the effects of integrated water and phosphorus on production performance and water-use efficiency and phosphorus-use efficiency of alfalfa, especially on hay yield, phosphorus accumulation, and total phosphorus uptake are rarely reported under drip irrigation. The treatments were a factorial combination of three irrigation rates (5,250, 6,000, and 6,750 m 3 /ha per year) and four P rates (0, 50, 100, and 150 kg/ha per year) and consisted of 12 treatments for water and P management, arranged in a randomized complete block design with three replicates. Total hay yield and water-use efficiency and phosphorus-use efficiency of alfalfa in P 2 treatment were significantly greater than those in the P 1 and P 3 treatments ( p  < .05), and the total hay yield of alfalfa with phosphorus application increased by 7.43%-29.87% compared with that in the nonphosphorus (P 0 ) treatment under the same irrigation amount. The total phosphorus and available phosphorus concentrations in the 0-20 cm soil layer were greater than those in the 20-40 cm and 40-60 cm soil layers compared with those in the P 0 treatment. Correlation analyses showed that total hay yield was significantly positively correlated with total phosphorus uptake and water-use efficiency ( p  < .01). The accumulated phosphorus concentration was significantly positively correlated with total phosphorus and available phosphorus concentration ( p  < .01) and was positively correlated with the phosphorus-use efficiency ( p  < .05). The membership function method was used to evaluate all the indicators, and the three treatments that had the greatest influence on the production performance of alfalfa were, in order, W 2 P 2  > W 3 P 2  > W 1 P 2 . Therefore, an irrigation rate of 6,000 m 3 /ha and a phosphorus application rate of 100 kg/ha per year should be considered as the best management for both high yield and water-use efficiency and phosphorus-use efficiency of alfalfa., Competing Interests: The authors declare that they have no conflict of interest., (© 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.)

Beet necrotic yellow vein virus (BNYVV) infections induce stunting and leaf curling, as well as root and floral developmental defects and leaf senescence in Nicotiana benthamiana . A microarray analysis with probes capable of detecting 1596 candidate microRNAs (miRNAs) was conducted to investigate differentially expressed miRNAs and their targets upon BNYVV infection of N. benthamiana plants. Eight species-specific miRNAs of N. benthamiana were identified. Comprehensive characterization of the N. benthamiana microRNA profile in response to the BNYVV infection revealed that 129 miRNAs were altered, including four species-specific miRNAs. The targets of the differentially expressed miRNAs were predicted accordingly. The expressions of miR164, 160, and 393 were up-regulated by BNYVV infection, and those of their target genes, NAC21/22 , ARF17/18 , and TIR , were down-regulated. GRF1 , which is a target of miR396, was also down-regulated. Further genetic analysis of GRF1, by Tobacco rattle virus -induced gene silencing, assay confirmed the involvement of GRF1 in the symptom development during BNYVV infection. BNYVV infection also induced the up-regulation of miR168 and miR398. The miR398 was predicted to target umecyanin , and silencing of umecyanin could enhance plant resistance against viruses, suggesting the activation of primary defense response to BNYVV infection in N. benthamiana . These results provide a global profile of miRNA changes induced by BNYVV infection and enhance our understanding of the mechanisms underlying BNYVV pathogenesis.

Background: Next generation sequencing (NGS) is a massively parallel sequencing technique that can be used to detect many forms of DNA variation, including point mutations, small fragment insertion deletions, gene recombination, and copy number variations. It can simultaneously analyze multiple genes and mutations, quantitatively detect gene mutation rate, and provide comprehensive information for clinicians. More and more lung cancer patients have benefited from studies on programmed death-1igand l (PD-L1) and immunocheckpoint inhibitors. The relationship between gene mutation and PD-L1 is also a focus of current research. Therefore, we collected a large number of cases to describe the molecular diagnostic characteristics of NGS in lung cancer and the relationship between NGS and PD-L1 expression., Method: A total of 1017 lung cancer patients with 15-gene panel (EGFR, ALK, ROS1, BRAF, MET, RET, ERBB2, KRAS, PIK3CA, KIT, ESR1, PDGFRA, DDR2, HRAS, NRAS) examined by NGS from our hospital were collected to analyze their clinicopathological characteristics. 600 of 1017 patients were tested for PD-L1 (22C3) by immunohistochemistry (IHC) at the same time. PD-L1 tumor proportion score (TPS) were used for comparative analysis with gene mutation results, and then to screen for possible correlation genes., Results: 74.63 % (759/1017) of lung cancer patients had at least one version of the genes. The top three mutation were EGFR (46.41 %), KRAS (13.86 %) and PIK3CA (10.03 %). Mutations in EGFR, KRAS, PIK3CA, KIT, ESR1 and NRAS were associated with sex (P < 0.05). Except for EGFR, which was more frequent in female, other genes were more frequent in male. ALK was more detectable in patients younger than 60, while PIK3CA was more detectable in patients older than 60(P < 0.05). EGFR, ALK, ROS1, KRAS, PIK3CA, ESR1 and NRAS were associated with smoking (P < 0.05). EGFR, KRAS, PIK3CA and ESR1 were correlated with pathological histology (P < 0.05). Among the 15 genes, only EGFR was associated with pathological histology of invasive adenocarcinoma (IA). EGFR had the highest mutation rate (60.00 %) in Lepidic predominate IA. Significantly different in sample types were found in EGFR, ALK, MET, KRAS, PIK3CA and NRAS examined by NGS. There were significant differences in the TPS of PD-L1 (22C3) in EGFR, ALK, BRAF and MET variants (P < 0.05). EGFR mutations were more common in TPS < 1 %, ALK mutations were more common in TPS (1 %-49 %), and BRAF and MET mutations were more common in TPS ≥ 50 %., Conclusion: In the 15-gene panel, in addition to EGFR, ALK and ROS1, MET, KRAS, PIK3CA, KIT, ESR1 and NRAS also had their own characteristics in sex, age, smoking history, histopathology, sample type and PD-L1, showing different clinicopathological tendencies. Understanding this information can help us optimize stratified lung cancer patients. Furthermore, it provides patients with a variety of diagnostic needs and a large number of unique clinical data worthy of clinical recognition., Competing Interests: Declaration of Competing Interest The authors state that there are no conflicts of interest to disclose., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Clopidogrel is one of the most frequently used drugs in patients to reduce cardiovascular events. Since patients with different genetic variations respond quite differently to clopidogrel therapy, the related genetic testing plays a vital role in its dosage and genetic testing related to clopidogrel therapy is currently considered as routine test worldwide. In this study, we aim to use two different methods MALDI-TOF mass spectrometry and pyrosequencing to detect gene variant of CYP2C19 and ABCB1. Six single nucleotides polymorphisms (SNP) within CYP2C19 (*2, *3, *4, *5, *17) and ABCB1 C3435T in 458 Chinese Han patients were determined using both MassARRAY and Pyrosequencing. Sanger sequencing was used for verification. Results of both methods were analyzed and compared. Allele frequencies of each SNP and distribution of different genotypes were calculated based on the MassARRAY and Sanger sequencing results. Both methods provided 100% call rates for gene variants, while results of six samples were different with two methods. With Sanger sequencing as the reference results, MassARRAY generated all the same results. The minor allele frequencies of the above six SNPs were 27.1% (CYP2C19*), 5.9% (CYP2C19*3), 0% (CYP2C19*4), 0% (CYP2C19*5), 1.1% (CYP2C19*17), 40.9% (ABCB1), respectively. MassARRAY provides accurate clopidogrel related genotyping with relatively high cost-efficiency, throughput and short time when compared with pyrosequencing.

Background: Previous studies examining the prognostic value of glucose transporter 1 in breast cancer have yielded inconsistent results. We, therefore, performed a meta-analysis to clarify this issue., Methods: The research was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Relevant studies were retrieved from PubMed, Web of Science, EMBASE, and Cochrane library., Results: A total of 7 reports with 1861 patients were finally chosen. GLUT1 overexpression was found to be associated with high histological grade (OR = 3.74, 95% CI = 2.45-5.69, P < .001), negative PR status (OR = 0.33, 95% CI = 0.22-0.49, P < .001), and negative estrogen receptor (ER) status (OR = 0.27, 95% CI = 0.17-0.42, P < .001). However, no significant correlation was seen between GLUT1 levels and presence of lymph node metastasis, tumor size or the status of human epidermal growth factor receptor 2 (HER2). Overexpression of GLUT1 also correlated with a poor overall survival (hazard ratio [HR] = 1.65, 95% confidence interval [CI] = 1.17-2.31, P = .004) and disease-free survival (HR = 2.35, 95% CI = 1.4-3.94, P < .001). No evidence of significant publication bias was found., Conclusion: This meta-analysis indicates that GLUT1 expression is associated with poor prognostic and a series of clinicopathological features in breast cancer. GLUT1 might be a potential biomarker and therapeutic target in breast cancer.

A capillary electrophoresis (CE) method was developed for the simultaneous separation and determination of four phenolic estrogens (PEs), in which pressure-assisted electrokinetic injection (PAEKI) was adopted as the on-line concentration method to enrich the PEs. Several parameters affecting PAEKI conditions such as injection voltage and injection time, were systematically investigated and compared with the usual parameters. Under the optimized PAEKI conditions (-9 kV, 0.3 psi (ca. 2.1 kPa), 0.4 min), the four PEs separated completely within 7 min. Good linearities were attained in the range of 0.05-5 mg/L for hexestrol and dienestrol, and 0.1-10 mg/L for bisphenol A and diethylstilbestrol, with correlation coefficients ( r ) over 0.9936. The limits of detection ( S/N =3) were 0.0071-0.017 mg/L, and enrichment factors ranged from 11 to 15 compared to normal hydrodynamic injection. The combined micellar electrokinetic chromatographic-PAEKI method developed was used to determine the PEs in tap water and lake water samples; limits of quantification ( S/N =10) of 0.029-0.064 mg/L and 0.033-0.079 mg/L were attained, respectively, by the two sample types. Furthermore, recoveries ranged from 75.6% to 110.1% with relative standard deviations ( n =5) within 4.6%-11.8%. To use this PAEKI method, researchers would only need to adjust the parameters of the CE apparatus to perform on-line enrichment of analytes, without using other reagents; this demonstrates the simplicity, rapidity, and highly automated nature of this method.

Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In the present study, we show that a short time exposure (3 h) to Triptolide, which did not trigger apoptosis, could specifically increase breast cancer cells sensitivity to Doxorubicin rather than other chemotherapy drugs including Paclitaxel, Fluorouracil, and Mitomycin C. Further studies revealed Triptolide downregulated ATM expression and inhibited DNA damage response to DNA double- strand breaks. Moreover, the chemosensitization effect to Doxorubicin from Triptolide was attenuated by overexpression of ATM in breast cancer cells. Our findings suggest that Triptolide specifically chemosensitizes breast cancer cells to Doxorubicin prior to apoptosis initiation through downregulating ATM expression and inhibiting DNA damage response., (© 2018 Wiley Periodicals, Inc.)