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Alterations in physiological processes in pancreas have been associated with various metabolic dysfunctions and can result from environmental exposures, such as chemicals and diet. It was reported that environmental vinyl chloride (VC) exposure, a common industrial organochlorine and environmental pollutant, significantly exacerbated metabolic-related phenotypes in mice fed concurrently with high-fat diet (HFD) but not low-fat diet (LFD). However, little is known about the role of the pancreas in this interplay, especially at a proteomic level. The present study was undertaken to examine the protein responses to VC exposure in pancreas tissues of C57BL/6J mice fed LFD or HFD, with focus on the investigation of protein expression and/or phosphorylation levels of key protein biomarkers of carbohydrate, lipid, and energy metabolism, oxidative stress and detoxification, insulin secretion and regulation, cell growth, development, and communication, immunological responses and inflammation, and biomarkers of pancreatic diseases and cancers. We found that the protein alterations may indicate diet-mediated susceptibility in mouse pancreas induced by HFD to concurrent exposure of low levels of inhaled VC. These proteome biomarkers may lead to a better understanding of pancreas-mediated adaptive or adverse response and susceptibility to metabolic disease.

With the globalization of communication nowadays, the needs of fashion brands are also increasing especially for those eastern brands, which appeared less in the global fashion stage before. This paper focuses on and explains how to conduct transcultural communication successfully for eastern brands based on the encoding and decoding theory proposed by Stuart Hall. Taking three cases of Japanese brand Issey Miyake for examples, this research analyzes how the brand encoded information in the advertisements and designs and then concludes three aspects of problems, different social contexts, orientalism stereotype and fashion system leaded by the west, to dig into the flash point of strategies of an eastern brand that is seen as successful internationally. Then universal implications matching with the problems, which are concluded in concrete cases, are provided for eastern brands to use for reference. The essay strives to explore for eastern brands in the cultural integration process of fashion industry.

Digitization of histologic slides brings with it the promise of enhanced toxicologic pathology practice through the increased application of computational methods. However, the development of these advanced methods requires access to substrate image data, that is, whole slide images (WSIs). Deep learning methods, in particular, rely on extensive training data to develop robust algorithms. As a result, pharmaceutical companies interested in leveraging computational methods in their digital pathology workflows must first invest in data infrastructure to enable data access for both data scientists and pathologists. The process of building robust image data resources is challenging and includes considerations of generation, curation, and storage of WSI files, and WSI access including via linked metadata. This opinion piece describes the collective experience of building resources for WSI data in the Roche group. We elaborate on the challenges encountered and solutions developed with the goal of providing examples of how to build a data resource for digital pathology analytics in the pharmaceutical industry.

Primary neuroendocrine breast carcinomas (NEBCs) are an extremely rare and underrecognized subtype of mammalian carcinoma. The prognostic factors for NEBCs remain controversial.In this multicenter retrospective study, the prognostic factors for patients with primary NEBCs who underwent surgery and had a pathologically confirmed diagnosis of neuroendocrine carcinoma in China and the United States were examined. The endpoints were disease-free survival (DFS) and overall survival (OS).A total of 51 Chinese patients and 98 US patients were included. In the Chinese cohort, tumor grade and Ki-67 levels were prognostic factors for DFS in univariate analysis (hazard ratio [HR] = 5.11 [1.67-15.60], p = 0.004; HR = 57.70 [6.36-523.40], p 0.001, respectively) and multivariate analysis (HR = 100.52 [1.33-7570.21], p = 0.037; HR = 31.47 [1.05-945.82], p = 0.047, respectively). In the US cohort, age was an important prognostic factor for OS in univariate analysis (HR = 1.09 [1.04-1.15], p = 0.001). The random effects model for the combined cohorts revealed age and positive expression of estrogen receptor (ER) as potential prognostic factors for OS (HR = 1.08 [1.01-1.14], p = 0.015; HR = 0.10 [0.02-0.44], p = 0.003, respectively).Tumor grade and Ki-67 levels are important prognostic factors for DFS of patients with primary NEBCs. Age and ER status are important prognostic factors for OS of patients with primary NEBCs.

Background Prompt and appropriate clinical management of malaria is critical for reducing the continued high burden of malaria among children under five years in sub-Saharan countries. However, more remains to be known about how a patient’s socioeconomic status (SES) would affect the access to diagnosis of malaria. Methods In this cross-sectional study using the Demographic and Health Survey and Malaria Indicators Survey, we pooled the data of 38,567 febrile under-five children in 2016–2018 from 19 sub-Saharan countries. Multivariable logistic regression was used to assess the associations between SES and two binary outcomes: the visit to a health facility and a blood test for fever. Stratified analyses were further conducted by the type of health facilities (public hospitals/public primary healthcare facilities/private hospitals/private primary healthcare facilities) for the latter outcome. Results Fifty-eight percent of the febrile children were taken to health facilities, among whom only 55% took blood tests. Compared to children from households in the highest wealth quintile, children in the lowest quintile were less likely to be taken to medical facilities [adjusted odds ratio (aOR) = 0.775, 95% confidence interval (CI): 0.675–0.889]. Parents with more than secondary education were more likely to seek care (aOR = 1.830, 95% CI: 1.561–2.145) and to have blood tests (aOR = 1.729, 95% CI: 1.436–2.082) for their febrile children than parents without formal education. The probabilities of receiving blood tests at public hospitals and public primary healthcare facilities stayed relatively high across parental education levels and wealth quintiles, while these probabilities remained the lowest at private primary healthcare facilities, ranging from 0.100 (95% CI: 0.074–0.127) to 0.139 (95% CI: 0.083–0.194) across parental education levels and from 0.104 (95% CI: 0.078–0.130) to 0.125 (95% CI: 0.090–0.160) across wealth quintiles. Conclusions Significant socioeconomic disparities existed both in the access to health facilities and laboratory diagnosis of malaria in children in sub-Saharan African countries. These disparities were particularly evident in the private sector. Universal health coverage needs to be further strengthened to make formal healthcare in general and the laboratory diagnosis of malaria more accessible and affordable. Graphical abstract

Background Kidney cancer undergoes a dramatic metabolic shift and has demonstrated responsiveness to immunotherapeutic intervention. However, metabolic classification and the associations between metabolic alterations and immune infiltration in Renal cell carcinoma still remain elucidative. Methods Unsupervised consensus clustering was conducted on the TCGA cohorts for metabolic classification. GESA, mRNAsi, prognosis, clinical features, mutation load, immune infiltration and differentially expressed gene differences among different clusters were compared. The prognosis model and nomograms were constructed based on metabolic gene signatures and verified using external ICGC datasets. Immunohistochemical results from Human Protein Atlas database and Tongji hospital were used to validate gene expression levels in normal tissues and tumor samples. CCK8, apoptosis analysis, qPCR, subcutaneously implanted murine models and flowcytometry analysis were applied to investigate the roles of ACAA2 in tumor progression and anti-tumor immunity. Results Renal cell carcinoma was classified into 3 metabolic subclusters and the subcluster with low metabolic profiles displayed the poorest prognosis, highest invasiveness and AJCC grade, enhanced immune infiltration but suppressive immunophenotypes. ACAA2, ACAT1, ASRGL1, AKR1B10, ABCC2, ANGPTL4 were identified to construct the 6 gene-signature prognosis model and verified both internally and externally with ICGC cohorts. ACAA2 was demonstrated as a tumor suppressor and was associated with higher immune infiltration and elevated PD-1 expression of CD8+ T cells. Conclusions Our research proposed a new metabolic classification method for RCC and revealed intrinsic associations between metabolic phenotypes and immune profiles. The identified gene signatures might serve as key factors bridging tumor metabolism and tumor immunity and warrant further in-depth investigations.

The serological diagnostic criteria for the immune-tolerant (IT) phase have not been strictly defined and it is hard to determine an accurate rate for significant histologic changes among IT patients. The aim of this study was to establish a baseline rate of significant histologic changes and to determine the main characteristics of IT patients. We systematically searched PubMed, Embase, and Web of Science. Studies reporting liver biopsy results (inflammation grade or fibrosis stage) for adults with chronic hepatitis B virus (HBV) infection in the IT phase diagnosed by serological criterion were included to pool the rate of significant histologic changes. Studies that enrolled subjects with confirmed chronic HBV infection in the IT phase diagnosed by serological and liver biopsy criteria (dual criteria) were included to pool the mean values of main characteristics among IT patients. Of 319 studies screened, 15 were eventually included in the meta-analysis. The pooled rates of significant liver fibrosis and inflammatory activity for 10 studies were 10% (95% confidence interval [CI] 0.06–0.18) and 16% (95% CI 0.07–0.31), respectively. The pooled mean values of age, alanine aminotransferase level, HBV DNA level, and HBsAg level for another 5 studies with IT patients diagnosed by dual criteria were 30.7 years (95% CI 27.31–34.09), 26.64 IU/mL (95% CI 24.45–28.83), 8.41 log10 cp/mL (95% CI 7.59–9.23), and 4.24 log10 IU/mL (95% CI 3.67–4.82), respectively. Significant histologic changes were not rare events among IT patients. Strictly defined serological diagnostic criteria for the IT phase are warranted.

Objectives Esophageal cancer is a high-mortality disease. Esophagectomy is the most effective method to treat esophageal cancer, accompanied with a high incidence of post-operation complications. The anastomosis has a close connection to many severe post-operation complications. However, it remains controversial about the choice of intrathoracic anastomosis (IA) or cervical anastomosis (CA). The study was conducted to compare the clinical outcomes between the two approaches. Methods We searched databases for both randomized controlled trials (RCTs) and cohort studies comparing post-operation outcomes between IA and CA. Primary outcomes were the incidences of anastomotic leakage and mortality. Secondary outcomes were the incidences of anastomotic stenosis, pneumonia and re-operation. Results Twenty studies with a total of 7,479 patients (CA group: n = 3,183; IA group: n = 4296) were included. The results indicated that CA group had a higher incidence of anastomotic leakage than IA group (odds ratio [OR] = 2.05, 95% confidence intervals [CI] = 1.61–2.60, I2 = 53.31%, P 2 = 0.00%, P = 0.04) and type II (OR = 2.75, 95%CI = 1.95–3.88, I2 = 1.80%, P 2 = 20.92%, P = 0.31). The 90-day mortality (OR = 1.66, 95%CI = 1.11–2.47, I2 = 0.0%, P = 0.01) in IA group were lower than that in CA group. No difference was found in in-hospital mortality (OR = 1.31, 95%CI = 0.91–1.88, I2 = 0.00%, P = 0.15) and 30-day mortality (OR = 1.08, 95%CI = 0.69–1.70, I2 = 0.00%, P = 0.74). Conclusions IA might be a better anastomotic approach than CA, with a lower incidence of anastomosis leakage and no increase in short-term mortality. Significant heterogeneity and publication bias might limit the reliability of the results. More high-quality studies are needed to verify and update our findings.

To investigate the effect of postmortem phases on lamb meat quality, the physicochemical quality, microstructure and water mobility of oyster cut, short loin, knuckle and silverside muscles from Small-Tail Han sheep were evaluated in the pre-rigor, rigor mortis and post-rigor phases. Pre-rigor lamb meat had higher pH and water holding capacity (WHC), whereas lower CIE L*, b*, hue angle values than rigor mortis and post-rigor meat (p

Background (−)-Limonene, one of cyclic monoterpenes, is an important renewable compound used widely as a key building block for the synthesis of new biologically active molecules and fine chemicals. (−)-Perillamine, as derived from (−)-limonene, is a highly useful synthon for constructing more complicated and functionally relevant chemicals. Aim We aimed to report a more sustainable and more efficient method for the regiospecific C–H amination of (−)-limonene into (−)-perillamine. Results Here, we report an artificial penta-enzymatic cascade system for the transformation of the cheap and easily available (−)-limonene into (−)-perillamine for the first time. This system is composed of cytochrome P450 monooxygenase, alcohol dehydrogenase and w-transaminase for the main reactions, as well as formate dehydrogenase and NADH oxidase for cofactor recycling. After optimization of the multi-enzymatic cascade system, 10 mM (−)-limonene was smoothly converted into 5.4 mM (−)-perillamine in a one-pot two-step biotransformation, indicating the feasibility of multi-enzymatic C7-regiospecific amination of the inert C–H bond of (−)-limonene. This method represents a concise and efficient route for the biocatalytic synthesis of derivatives from similar natural products.

Three unusual diterpenes with rare sarsolenane and capnosane skeletons, namely mililatensols A-C (

Naringenin (NN) is one of the most abundant flavonoids in citrus and grapefruits and has been shown to have antioxidant properties in vitro. The purpose of the study is to examine the antioxidant and anti-aging activities of NN in C. elegans, and to further explore the molecular mechanism. The results showed that NN enhanced the lifespan under normal and oxidative stress induced by H2O2. After treatment with NN, locomotion capability was improved and aging pigment accumulation was suppressed. NN also delayed the paralysis and reversed the defective chemotaxis behavior induced by Aβ protein. Meanwhile, the treatment with NN enhanced the activities of antioxidant enzymes and reduced the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) content. The possible targets and pathways interacting with NN were predicted by network pharmacology. Real-time PCR analysis indicated that NN upregulated the expression levels of daf-16, sek-1 and skn-1, downregulated the expression levels of daf-2, age-1 and akt-1, and further activated sod-3, ctl-1, ctl-2, gst-4 and mtl-1. Moreover, the selected mutant strains were used and molecular docking was conducted to further suggest that IIS and MAPK pathways could be involved in the NN-mediated longevity-promoting effect.

Two new sesquiterpenoids, flammupin A (

Background (−)-Limonene, one of cyclic monoterpenes, is an important renewable compound used widely as a key building block for the synthesis of new biologically active molecules and fine chemicals. (−)-Perillamine, as derived from (−)-limonene, is such a useful synthon for constructing more complicated and functionally relevant chemicals. Aim We aimed to report a more sustainable and more efficient method for the regiospecific C-H amination of (−)-limonene into (−)-perillamine. Results Here we report an artificial penta-enzymatic cascade system for the transformation of the cheap and easily available (−)-limonene into (−)-perillamine for the first time. This system is composed of cytochrome P450 monooxygenase, alcohol dehydrogenase and w-transaminase for the main reactions, as well as formate dehydrogenase and NADH oxidase for cofactor recycling. After optimization of the multi-enzymatic cascade system, 10 mM (−)-limonene was smoothly converted into 5.4 mM (−)-perillamine in a one-pot-two-step biotransformation, indicating the feasibility of multi-enzymatic C7-regiospecific amination of the inert C-H bond of (−)-limonene. This method represents a concise and efficient route for the biocatalytic synthesis of derivatives from similar natural products.

Objectives To predict kidney fibrosis in patients with chronic kidney disease using radiomics of two-dimensional ultrasound (B-mode) and Sound Touch Elastography (STE) images in combination with clinical features. Methods The Mindray Resona 7 ultrasonic diagnostic apparatus with SC5-1U convex array probe (bandwidth frequency of 1–5 MHz) was used to perform two-dimensional ultrasound and STE software. The severity of cortical tubulointerstitial fibrosis was divided into three grades: mild interstitial fibrosis and tubular atrophy (IFTA), fibrotic area < 25%; moderate IFTA, fibrotic area 26–50%; and severe IFTA, fibrotic area > 50%. After extracting radiomics from B-mode and STE images in these patients, we analyzed two classification schemes: mild versus moderate-to-severe IFTA, and mild-to-moderate versus severe IFTA. A nomogram was constructed based on multiple logistic regression analyses, combining clinical and radiomics. The performance of the nomogram for differentiation was evaluated using receiver operating characteristic (ROC), calibration, and decision curves. Results A total of 150 patients undergoing kidney biopsy were enrolled (mild IFTA: n = 74; moderate IFTA: n = 33; severe IFTA: n = 43) and randomized into training (n = 105) and validation cohorts (n = 45). To differentiate between mild and moderate-to-severe IFTA, a nomogram incorporating STE radiomics, albumin, and estimated glomerular filtration (eGFR) rate achieved an area under the ROC curve (AUC) of 0.91 (95% confidence interval [CI]: 0.85–0.97) and 0.85 (95% CI: 0.77–0.98) in the training and validation cohorts, respectively. Between mild-to-moderate and severe IFTA, the nomogram incorporating B-mode and STE radiomics features, age, and eGFR achieved an AUC of 0.93 (95% CI: 0.89–0.98) and 0.83 (95% CI: 0.70–0.95) in the training and validation cohorts, respectively. Finally, we performed a decision curve analysis and found that the nomogram using both radiomics and clinical features exhibited better predictability than any other model (DeLong test, p < 0.05 for the training and validation cohorts). Conclusion A nomogram based on two-dimensional ultrasound and STE radiomics and clinical features served as a non-invasive tool capable of differentiating kidney fibrosis of different severities. Key Points • Radiomics calculated based on the ultrasound imaging may be used to predict the severities of kidney fibrosis. • Radiomics may be used to identify clinical features associated with the progression of tubulointerstitial fibrosis in patients with CKD. • Non-invasive ultrasound imaging-based radiomics method with accuracy aids in detecting renal fibrosis with different IFTA severities.

Micro-expressions are fleeting and subtle emotional expressions. As they are spontaneous and uncontrollable by one’s mind, micro-expressions are considered an indicator of genuine emotions. Their accurate recognition and interpretation promote interpersonal interaction and social communication. Therefore, enhancing the ability to recognize micro-expressions has captured much attention. In the current study, we investigated the effects of training on micro-expression recognition with a Chinese version of the Micro-Expression Training Tool (METT). Our goal was to confirm whether the recognition accuracy of spontaneous micro-expressions could be improved through training and brain stimulation. Since the right temporal parietal junction (rTPJ) has been shown to be involved in the explicit process of facial emotion recognition, we hypothesized that the rTPJ would play a role in facilitating the recognition of micro-expressions. The results showed that anodal transcranial direct-current stimulation (tDCS) of the rTPJ indeed improved the recognition of spontaneous micro-expressions, especially for those associated with fear. The improved accuracy of recognizing fear spontaneous micro-expressions was positively correlated with personal distress in the anodal group but not in the sham group. Our study supports that the combined use of tDCS and METT can be a viable way to train and enhance micro-expression recognition.

Background and Purpose The pulmonary vascular remodeling (PVR), the pathological basis of pulmonary hypertension (PH), entails pulmonary artery smooth muscle cells (PASMCs) phenotypic switching, but appreciation of the underlying mechanisms is incomplete. Exosomes, a novel transfer machinery enabling delivery of its cargos to recipient cells, have been recently implicated in PH. The two critical questions of whether plasma-derived exosomes drive PASMCs phenotypic switching and what cargo the exosomes transport, however, remain unclear. Experimental Approach PH is induced by exposure of rats to chronic hypoxia (10% O2, 3 weeks). Exosomes were isolated and purified from rat plasma by ultracentrifugation. Exosomal LOX-1 was assessed by transmission electron microscopy and Western blotting. PASMCs phenotypic switching was determined by Western blotting, immunofluorescence staining and flow cytometry. Key Results We characterized lectin like oxidized low-density lipoprotein receptor-1 (LOX-1) as a novel cargo of plasma-derived exosomes in PH. With LOX-1 knockout (Olr1-/-) rats-derived exosomes, we demonstrated that exosomal LOX-1 could be transferred into PASMCs and thus elicited cell phenotypic switching. Of importance, Olr1-/- rats exhibited no cell phenotypic switching and developed less severe PH, but administration of wild type rather than Olr1-/- exosomes to Olr1-/- rats recapitulated the phenotype of PH with robust PASMCs phenotypic switching. We also revealed that exosomal LOX-1 triggered PASMCs phenotypic switching, PVR and ultimately PH via ERK1/2-KLF4 signaling axis. Conclusion and Implications This study has generated proof that plasma-derived exosomes confer PH by delivering LOX-1 into PASMCs. Hence, exosomal LOX-1 represents a novel exploitable target for PH prevention and treatment.

Background & aims Sarcopenia is associated with poor clinical outcomes of patients who underwent esophagectomy. The current diagnostic criteria for sarcopenia are complex and laborious. We aimed to employ the simple and economic indicator sarcopenia index (SI = creatinine/cystatin C ×100) to screen for sarcopenia and to evaluate its prognostic value in patients with esophageal cancer (EC). Methods Older participants in the National health and nutrition examination survey (NHANES) database (1999–2002) were divided into three groups according to tertiles of the SI value to explore the feasibility of SI in the diagnosis of sarcopenia. Restricted cubic spline (RCS) was utilized to show the non-linear relationship between all-cause mortality and SI. Patients with EC admitted to Jinling Hospital were enrolled to validate the efficacy and prognostic value of SI. Cut-off values of SI were determined using receiver operating characteristic curves. Multivariable logistic analyses and Cox analyses were used to identify the independent factors of postoperative complications and long-term survival, respectively. Results A total of 989 participants were identified from the NHANES database. SI showed the diagnostic value of sarcopenia (tertile 1 vs. tertile 3: odds ratio [OR]=3.67, 95% confidence interval [CI]: 1.52–8.87, p=0.004; tertile 2 vs. tertile 3: OR=1.79, 95% CI: 0.75–4.28, p=0.191) adjusted for race, gender, and body mass index (BMI). Individuals with SI ≤ 68 had a poorer overall survival (OS) (hazard ratio [HR]=2.14, 95% CI: 1.71–2.68, ppp=0.046). Conclusion SI could be used to identify sarcopenia in patients with EC, and it is a useful prognostic factor of postoperative complications and long-term survival.

The development of eco-friendly lubricant additives is of great significance for environmental protection. In this study, cellulose nanocrystal (CNC) was prepared and added into four lithium-based greases with different consistencies and apparent viscosities. The results suggest that the concentration of doped CNC should be limited to a certain value (5 wt% to 10 wt% depending on the grease type) to avoid excessive variation on the basic physical properties of greases. In the pristine grease with low consistency (NLGI grade 1) the incorporated CNC could be effectively transported through the fibrous network and deposited on the sliding surface. Through the surface mending and protection by CNC additive, together with the strong hydrodynamic effect of the high viscous base oil (220 cSt at 40 °C), the biggest reduction of friction and wear was achieved by 16% and 29% respectively. This study reveals the lubrication mechanism and application strategy of CNC in greases.

Human mobility studies have become increasingly important and diverse in the past decade with the support of social media big data that enables human mobility to be measured in a harmonized and rapid manner. However, what is less explored in the current scholarship is episodic mobility as a special type of human mobility defined as the abnormal mobility triggered by episodic events excess to the normal range of mobility at large. Drawing on a large-scale systematic collection of 1.9 billion geotagged Twitter data from 2017 to 2020, this study contributes to the first empirical study of episodic mobility by producing a daily Twitter census of visitors at the U.S. county level and proposing multiple statistical approaches to identify and quantify episodic mobility. It is followed by four case studies of episodic mobility in U.S. national wide to showcase the great potential of Twitter data and our proposed method to detect episodic mobility subject to episodic events that occur both regularly and sporadically. This study provides new insights on episodic mobility in terms of its conceptual and methodological framework and empirical knowledge, which enriches the current mobility research paradigm.

Clear cell renal cell carcinoma (ccRCC) is considered to be related to the worse prognosis, which might in part be attributed to the early recurrence and metastasis, compared with other type of kidney cancer. Oxidative stress refers to an imbalance between production of oxidants and antioxidant defense. Accumulative studies have indicated that oxidative stress genes contribute to the tumor invasion, metastasis and drug sensitivity. However, the biological functions of oxidative stress genes in ccRCC remain largely unknown. In this study, we identified 1,399 oxidative stress genes from GeneCards with a relevance score ≥7. Data for analysis were accessed from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database, and were utilized as training set and validation set respectively. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox were employed to construct a prognostic signature in ccRCC. Finally, a prognostic signature including four different oxidative stress genes was constructed from 1,399 genes, and its predictive performance was verified through Kaplan-Meier survival analysis and the receiver operating characteristic (ROC) curve. Interestingly, we found that there was significant correlation between the expression of oxidative stress genes and the immune infiltration and the sensitivity of tumor cells to chemotherapeutics. Moreover, the highest hazard ratio gene urocortin (UCN) was chosen for further study; some necessary vitro experiments proved that the UCN could promote the ability of ccRCC proliferation and migration and contribute to the degree of oxidative stress. In conclusion, it was promising to predict the prognosis of ccRCC through the four oxidative stress genes signature. UCN played oncogenic roles in ccRCC by influencing proliferation and oxidative stress pathway, which was expected to be the novel therapeutic target for ccRCC.

Documents on the chemical composition of the soft coral Sarcophyton mililatensis are sparse. The present investigation of the Hainan soft coral S. mililatensis resulted in the discovery of six new cembrane diterpenes, sarcoxacyclols A–F (1–6) and four known analogs (7–10). Their structures were elucidated by extensive spectroscopic analysis along with a comparison with the data in current literature. The nonaromatic oxacycles in their structures were the rarely found tetrahydrofuran ether across C-1 and C-12 and tetrahydropyran ether across C-1 and C-11, respectively. Moreover, the absolute configuration of compound 4 was established unambiguously by X-ray diffraction analysis using Ga Kα radiation (λ = 1.34139 Å). Based on the biogenetical consideration, the absolute configurations of other five new compounds were tentatively assumed. Assessment of the bioactivity for these secondary metabolites revealed that compound 1 exhibited significant tumor necrosis factor (TNF)-α inhibitory activity (IC50 = 9.5 μmol/L), similar to the positive control dexamethasone (IC50 = 8.7 μmol/L), but no obvious cytotoxicity towards RAW264.7 cells (CC50 > 50 μmol/L). The preliminary molecular docking suggested the crucial roles of the hydroxyl and acetoxyl groups in the computational prediction of the binding mode between the diterpene and the protein.

The presence of Per-, Poly-fluoroalkyl substances (PFASs) in aquatic ecosystems has drawn broad concerns in the scientific community due to their biological toxicity. However, little has been explored regarding PFASs' removal in phytoplankton-dominated environments. This study aimed to create a simulated bacteria-algae symbiotic ecosystem to observe the potential transportation of PFASs. Mass distributions showed that sand (63-2000 μm), siltclay (0-63 μm), the phycosphere (3 μm plankton), and the free-living biosphere (0.22-3 μm plankton) contained 19.00, 7.78, 5.73 and 2.75% PFASs in their total mass, respectively. Significant correlations were observed between carbon chain lengths and removal rates (R

A new label-free electrochemical immunosensor was constructed for quantitative detection of procalcitonin (PCT), by employing AuPtCu nanodendrites (AuPtCu NDs, prepared by a one-pot solvothermal method) and graphene-wrapped Co nanoparticles encapsulated in 3D N-doped carbon nanobrushes (G-Co@ NCNBs), obtained by self-catalyzed chemical vapor deposition as immune-sensing platform. Impressively, the home-made nanocomposite enlarged the highly accessible active sites and promoted the mass/electron transport, in turn showing the efficient synergistic catalysis towards H

Naringenin (NN) is one of the most abundant flavonoids in citrus and grapefruits and has been shown to have antioxidant properties

Pancreatic β-cell dysfunction is a key link during the progression of type 2 diabetes (T2DM), and SIRT1 participates in the regulation of various physiological activities of islet β-cells. However, as a key link in signal transduction, it is not clear how SIRT1 is regulated. By TargetScan prediction, we found that miR-204, which is enriched in islets, has highly complementary binding sites with SIRT1. Therefore, we speculate that miR-204 may be the upstream regulatory target of SIRT1 in islets and thus participate in the occurrence of β-cell dysfunction. In this study, we explored the association between miR-204 and β-cell dysfunction, the therapeutic effects of berberine (BBR) on β-cell function and the possible mechanisms. We found that miR-204 increased and SIRT1 mRNA and protein levels decreased significantly in islets both in vivo and in vitro. MIN6 cells induced by palmitic acid exhibited increased apoptosis, and the accumulation of insulin and ATP in the supernatant decreased. Importantly, palmitic acid treatment combined with miR-204 silencing showed opposite changes. MiR-204 overexpression in MIN6 cells increased apoptosis and decreased insulin and ATP production and SIRT1 expression. SIRT1 overexpression reversed the damage to β-cells caused by miR-204. The BBR treatment effectively improved insulin synthesis, reduced miR-204 levels, and increased SIRT1 expression in islet tissue in diabetic mice. Overexpression of miR-204 reversed the protective effect of BBR on apoptosis and insulin secretion in MIN6 cells. Our study identifies a novel correlation between miR-204 and β-cell dysfunction in T2DM and shows that administration of BBR leads to remission of β-cell dysfunction by regulating the miR-204/SIRT1 pathway.

Searchable encryption (SE) allows users to search over encrypted data without decrypting. In most existing SE schemes, server returns all matched files without relevance ranking, and the update mechanism are suffering with high communication and computation cost, which are not efficient enough to satisfy the real-life dynamic scenario. Addressing the above issues, we proposed TS-RDSE-a Two-Server Ranked Dynamic Searchable Encryption scheme. We integrate orthogonal vector and efficient homomorphic encryption cryptosystems to build a vector-level dynamic secure index, which simultaneously supports efficient dynamic update operations like deletion and insertion of files flexibly. Moreover, in order to rank the search results by relevance without decryption, we build a secure sorting protocol based on the widely-used tf-idf weighting formula and addition property of partial homomorphic encryption, which achieves accurate sorting for the search results while protecting the privacy of relevance scores. We give a comprehensive analysis of the correctness of TS-RDSE in the aspect of searching and sorting with mathematical proofs. The security analysis shows that TS-RDSE is secure against adaptive dynamic chosen-keyword attacks (CKA2) by honest-but-curious adversaries in random oracle model. The performance analysis shows that TS-RDSE has both a very light user workload and a moderate server workload, and it is superior to the existing approaches in terms of functionalities and expansibility. Extensive experiments on the real-world dataset validate our analysis and show that TS-RDSE is suitable for the real world cloud storage environment.

Magnetization roasting and magnetic separation is an effective method of recovering iron from low-grade ores. The phase transformation mechanism of minerals is an important basis for optimizing technological parameters. In this study, biomass was used as a reducing agent to roast Baotou low-grade limonite in a high-temperature vacuum furnace. The phase transformation law and its influence on magnetic properties were studied via X-ray diffraction, scanning electron microscopy, and vibrating sample magnetometry. The results show that roasting temperature is related to the magnetism of iron ore. With an increase in temperature, iron content increases gradually, and limonite magnetism also increases, at 700 °C reaching a maximum saturation magnetization of iron concentrate of 43.06 emu/g. It was also found that during vacuum roasting, S elements migrated and accumulated on the surface of limonite and distributed evenly on the surface of mineral particles in the form of FeS, forming ash shells.

Aim Growing evidence suggests that endothelial-mesenchymal transition (EndMT) play key roles in pulmonary arterial remodeling during pulmonary arterial hypertension (PAH), but the underlying mechanisms have yet to be fully understood. miR-27a has been shown to promote proliferation of pulmonary arterial cells during PAH, but its role in EndMT remains unexplored. This study was designed to investigate the role and underlying mechanism of miR-27a in EndMT during PAH. Main methods Rats were exposed in hypoxia (10% O2) for 3 weeks to induce PAH, and human pulmonary artery endothelial cells (HPAECs) were exposed in hypoxia (1% O2) for 48 h to induce EndMT. Immunohistochemistry, in situ hybridization, immunofluorescence, real-time PCR and Western blot were conducted to detect the expressions of RNAs and proteins, and luciferase assay was used to verify the putative binding site of miR-27a. Key findings We found that hypoxia up-regulated miR-27a in the tunica intima of rat pulmonary arteries and HPAECs, and that inhibition of miR-27a suppressed hypoxia-induced EndMT. Furthermore, elevated expression of miR-27a suppressed bone morphogenetic protein (BMP) signaling by targeting Smad5, thereby lessening Id2-mediated repression of the 2 critical mediators of EndMT (Snail and Twist). Significance Our data unveiled a novel role of miR-27a in EndMT during hypoxia-induced PAH. Thus, targeting of miR-27a-related pathway may be therapeutically harnessed to treat PAH.

The relationship between androgen receptor expression and renal cell carcinoma risk remains controversial. This study is aimed to investigate the clinical significance of androgen receptor expression in renal cell carcinoma. A computerized bibliographic search of Embase, the PubMed, and Web of Science combined with manual research between 1977 and 2017 was conducted to explore the association between androgen receptor expression and clinicopathological features of renal cell carcinoma. Data were analyzed by a meta-analysis using RevMan 5.3 analysis software. Eleven retrospective studies with 1839 renal cell carcinoma cases were finally included according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. It was found that there was no significant difference between androgen receptor expression and susceptibility, pathological type, metastatic status, metastatic type (lymph or distant metastasis) and cancer-specific survival of renal cell carcinoma (P > 0.05). However, positive androgen receptor expression was demonstrated to be significantly associated with male patients, lower pathological grade, and earlier tumor stage of renal cell carcinoma (OR = 1.69, 95% CI = 1.30–2.19, P

Three unusual diterpenes with rare sarsolenane and capnosane skeletons, namely mililatensols A–C (1–3), were isolated from the South China Sea soft coral Sarcophyton mililatensis, leading to the first record of sarsolenane and capnosane diterpenes from the title animal. The structures of compounds 1–3 were established by extensive spectroscopic analysis and comparison with the literature data. Moreover, the absolute configuration of 2 was determined by TDDFT ECD calculations. In an in vitro bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages. In the preliminary virtual screening of inhibitory potential against SARS-CoV-2 by molecular docking, the results showed these three diterpenes were potential SARS-CoV-2 Mpro inhibitors.

The plasma window is a windowless vacuum sealing device that utilizes a cascade arc discharge to isolate regions with different pressures. It was proposed as an alternative to the traditional windowless sealing technology of differential pumping, which greatly improves the sealing efficiency and has been successfully applied in electron beam welding. The discharge channel of the existing plasma window is a small circular hole, referred to as a zero-dimensional plasma window, which has limited applications to its dimensions. In this study, we suggested a one-dimensional (1D) plasma window with a slit discharge channel (cross section: 3 × 35 mm2, length: 60 mm). An arc discharge is realized with the support of an 80 A DC power supply, which can maintain a pressure drop of more than 10 times between the high-pressure and low-pressure ends of the plasma window. A COMSOL-based magneto-hydrodynamic model of the plasma window was established, and simulations were in good agreement with the experimental results. The pressure drop in the plasma window caused by argon plasma has also been theoretically analyzed and discussed. The feasibility of a 1D plasma window to achieve vacuum isolation was verified theoretically, numerically, and experimentally.

Background Anemia in pregnancy is behind a significant burden of maternal mortality and poor birth outcomes globally. Efforts to address it need evidence on trends and its pertinent factors as they vary from one area to another. Methods We pooled data of 23,203 women of reproductive age whose hemoglobin levels were measured from two Tanzania Demographic and Health Surveys (TDHS). Of them, 2,194 women were pregnant. Analyses employed descriptive analyses to determine the burden of anemia, its characteristics, and severity; GIS mapping to determine the regional changes of anemia between 2005 and 2015; and logistic regression to determine the remaining determinants of anemia among pregnant women using Stata 15. Results The burden of anemia among pregnant women in Tanzania has remained unprecedently high, and varies between regions. There was no significant decline of anemia in general between the two periods after adjusting for individual, households, reproductive, and child characteristics [AOR = 0.964, 95% CI = 0.774–1.202, p = 0.747). Anemia is currently prevalent in 57% of pregnant women in Tanzania. The prevalence is more likely to be higher among women aged 15–19 years than those aged between 20–34 years. It is more likely to be prevalent among those within large families, with no formal education, food insecurity, lack of health insurance, had no antimalaria during pregnancy, and had low frequency of ANC attendance. On the other hand, delivery in a health facility may be potentially protective against anemia. Conclusions Anemia in pregnancy remained persistently high and prevalent among 57% of pregnant women in Tanzania. Efforts to address anemia are crucial and need to be focused in regions with increasing burden of anemia among pregnant women. It is imperative to address important risk factors such as food insecurity, strengthening universal health coverage, empowering women of reproductive age with education and especially nutritional knowledge and advocating for early antenatal booking, attendance, and facility delivery.

Continuous recruitment and inappropriate activation of platelets in pulmonary arteries contribute to pulmonary vascular remodeling in pulmonary hypertension (PH). Our previous study has demonstrated that lectin like oxidized low-density lipoprotein receptor-1 (LOX-1) regulates the proliferation of pulmonary arterial smooth muscle cells (PASMCs). Phosphatidylserine exposed on the surface of activated platelets is a ligand for LOX-1. However, whether hypoxia-activated platelets stimulate the proliferation and migration of PASMCs by phosphatidylserine/LOX-1 signaling-impelled intercellular communication remains unclear. The present study found that rats treated with hypoxia (10% O2) for 21 days revealed PH with the activation of platelets and the recruitment of platelets in pulmonary arteries, and LOX-1 knockout inhibited hypoxia-induced PH and platelets activation. Notably, co-incubation of PASMCs with hypoxic PH rats-derived platelets up-regulated LOX-1 expression in PASMCs leading to the proliferation and migration of PASMCs, which was inhibited by the phosphatidylserine inhibitor annexin V or the LOX-1 neutralizing antibody. LOX-1 knockout led to decreased proliferation and migration of PASMCs stimulated by hypoxia-activated platelets. In rats, hypoxia up-regulated the phosphorylation of signal transducer and activator of transcription 3 (Stat3) and the expression of Pim-1 in pulmonary arteries. Hypoxia-activated platelets also up-regulated the phosphorylation of Stat3 and the expression of Pim-1 in PASMCs, which was inhibited by annexin V, the LOX-1 neutralizing antibody, the protein kinase C inhibitor and LOX-1 knockout. In conclusion, we for the first time demonstrated that hypoxia-activated platelets stimulated the proliferation and migration of PASMCs by phosphatidylserine/LOX-1/PKC/Stat3/Pim-1 signaling-impelled intercellular communication, thereby potentially contributing to hypoxic pulmonary vascular remodeling.

Dysregulation of transcription factors contributes to the carcinogenesis and progression of cancers. However, their roles in clear cell renal cell carcinoma remain largely unknown. This study aimed to evaluate the clinical significance of TFs and investigate their potential molecular mechanisms in ccRCC. Data were accessed from the cancer genome atlas kidney clear cell carcinoma cohort. Bioinformatics algorithm was used in copy number alterations mutations, and differentially expressed TFs’ analysis. Univariate and multivariate Cox regression analyses were performed to identify clinically significant TFs and construct a six-TF prognostic panel. TFs’ expression was validated in human tissues. Gene set enrichment analysis (GSEA) was utilized to find enriched cancer hallmark pathways. Functional experiments were conducted to verify the cancer-promoting effect of BARX homeobox 1 (BARX1) and distal-less homeobox 4 (DLX4) in ccRCC, and Western blot was performed to explore their downstream pathways. As for results, many CNAs and mutations were identified in transcription factor genes. TFs were differentially expressed in ccRCC. An applicable predictive panel of six-TF genes was constructed to predict the overall survival for ccRCC patients, and its diagnostic efficiency was evaluated by the area under the curve (AUC). BARX1 and DLX4 were associated with poor prognosis, and they could promote the proliferation and migration of ccRCC. In conclusion, the six-TF panel can be used as a prognostic biomarker for ccRCC patients. BARX1 and DLX4 play oncogenic roles in ccRCC via promoting proliferation and epithelial–mesenchymal transition. They have the potential to be novel therapeutic targets for ccRCC.

Developing a highly sensitive immunoassay for tumor biomarkers is particularly important in bioanalysis and early disease diagnosis. In this work, a simple one-pot solvothermal method was developed for controllable synthesis of well-dispersed PtCo alloyed nanodendrites (PtCo NDs) by using l -carnosine as the co-structure-directing agent. The PtCo NDs had a large specific surface area and provided abundant active sites available for electrocatalytic oxygen reduction reaction (ORR). Based on the highly enhanced currents of the ORR, a novel label-free electrochemical immunosensor was fabricated for highly sensitive assay of carbohydrate antigen 15–3 (CA15-3). The sensor showed a wide linear range of 0.1–200 U mL−1 and a low limit of detection (LOD) down to 0.0114 U mL−1 (S/N = 3), in turn exploring its application to diluted human serum samples with satisfactory results. This study provides a feasible platform for monitoring other tumor markers in clinical diagnosis.

Pulmonary vascular remodeling (PVR) is the pathological basis of pulmonary hypertension (PH). Incomplete understanding of PVR etiology has hindered drug development for this devastating disease, which exhibits poor prognosis despite the currently available therapies. Endothelial-to-mesenchymal transition (EndMT), a process of cell transdifferentiation, has been recently implicated in cardiovascular diseases, including PH. But the questions of how EndMT occurs and how to pharmacologically target EndMT in vivo have yet to be further answered. Herein, by performing hematoxylin-eosin and immunofluorescence staining, transmission electron microscopy and Western blotting, we found that EndMT plays a key role in the pathogenesis of PH, and importantly that aspirin, a FDA-approved widely used drug, was capable of ameliorating PVR in a preclinical rat model of hypoxia-induced PH. Moreover, aspirin exerted its inhibitory effects on EndMT in vitro and in vivo by suppressing HIF-1α/TGF-β1/Smads/Snail signaling pathway. Our data suggest that EndMT represents an intriguing drug target for the prevention and treatment of hypoxic PH and that aspirin may be repurposed to meet the urgent therapeutic needs of hypoxic PH patients.