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The mediastinum contains essentially all major intrathoracic organs except for the lungs. A variety of both benign and malignant tumors can involve the mediastinum, of which lymphoma is the most common malignancy. Compared to secondary mediastinal involvement by systemic lymphomas, primary mediastinal lymphomas are less common with several specific entities that are mainly confined to mediastinal lymph nodes, and/or thymus. This review will summarize the clinical, histologic, immunophenotypic and molecular genetic features of the most common and most aggressive primary mediastinal lymphomas as well as provide suggested immunohistochemistry panels and differential diagnoses., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Hippo signaling is instrumental in regulating organ size, regeneration, and carcinogenesis. The cytoskeleton emerges as a primary Hippo signaling modulator. Its structural alterations in response to environmental and intrinsic stimuli control Hippo signaling pathway activity. However, the precise mechanisms underlying the cytoskeleton regulation of Hippo signaling are not fully understood. RAP2 GTPase is known to mediate the mechanoresponses of Hippo signaling via activating the core Hippo kinases LATS1/2 through MAP4Ks and MST1/2. Here we show the pivotal role of the reciprocal regulation between RAP2 GTPase and the cytoskeleton in Hippo signaling. RAP2 deletion undermines the responses of the Hippo pathway to external cues tied to RhoA GTPase inhibition and actin cytoskeleton remodeling, such as energy stress and serum deprivation. Notably, RhoA inhibitors and actin disruptors fail to activate LATS1/2 effectively in RAP2-deficient cells. RNA sequencing highlighted differential regulation of both actin and microtubule networks by RAP2 gene deletion. Consistently, Taxol, a microtubule-stabilizing agent, was less effective in activating LATS1/2 and inhibiting cell growth in RAP2 and MAP4K4/6/7 knockout cells. In summary, our findings position RAP2 as a central integrator of cytoskeletal signals for Hippo signaling, which offers new avenues for understanding Hippo regulation and therapeutic interventions in Hippo-impaired cancers., Competing Interests: Conflict of interest The authors declare no conflict of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Malignant pleural effusion is mostly a complication of advanced malignant tumors. However, the cancer markers such as carbohydrate antigen 125 (CA 125), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), and cytokeratin fragment 21-1 (CYFRA 21-1) have low sensitivity and organ specificity for detecting malignant pleural effusion., Research Question: Is IR808@MnO nano-near infrared fluorescent dye worthy for the diagnosis in differentiating benign and malignant pleural effusions., Study Design and Methods: This experiment was carried out to design and characterize the materials for in vitro validation of the new dye in malignant tumor cells in the A549 cell line and in patients with adenocarcinoma pleural effusion. The dye was verified to possess tumor- specific targeting capabilities. Subsequently, a prospective hospital-based observational study was conducted, enrolling 106 patients and excluding 28 patients with unknown diagnoses. All patients underwent histopathological analysis of thoracoscopic biopsies, exfoliative cytological analysis of pleural fluid, and analysis involving the new dye. Statistical analyses were performed using Microsoft Excel, GraphPad Prism, and the R language., Results: The size of IR808@MnO was 136.8 ± 2.9 nm, with peak emission at 808 nm, and it has near-infrared fluorescence properties. Notably, there was a significant difference in fluorescence values between benign and malignant cell lines (p < 0.0001). The malignant cell lines tested comprised CL1-5, A549, MDA-MB-468, U-87MG, MKN-7, and Hela, while benign cell lines were BEAS-2B, HUVEC, HSF, and VE. The most effective duration of action was identified as 30 min at a concentration of 5 μl. This optimal duration of action and concentration were consistent in patients with lung adenocarcinoma accompanied by pleural effusion and 5 μl. Of the 106 patients examined, 28 remained undiagnosed, 39 were diagnosed with malignant pleural effusions, and the remaining 39 with benign pleural effusions. Employing the new IR808@MnO staining method, the sensitivity stood at 74.4%, specificity at 79.5%, a positive predictive value of 69.2%, and a negative predictive value of 82.1%. The area under the ROC curve was recorded as 0.762 (95% CI: 0.652-0.872). The confusion matrix revealed a positive predictive value of 75.7%, a negative predictive value of 75.6%, a false positive rate of 22.5%, and a false negative rate of 26.3%., Interpretation: The IR808@MnO fluorescent probe represents an efficient, sensitive, and user-friendly diagnostic tool for detecting malignant pleural fluid, underscoring its significant potential for clinical adoption., (© 2024. The Author(s).)

Rat primitive extraembryonic endoderm (pXEN) stem cell lines indefinitely preserve the characteristic features of the early extraembryonic endoderm (ExEn) in vitro, but require unknown serum factors and exhibit a hybrid (mesenchymal-epithelial) phenotype. We report two chemically defined conditions that differ by the addition of the cytokine leukemia inhibitory factor (Lif) and the β-catenin-stabilizing drug Chir99021, and enable permanent self-renewal as mesenchymal and epithelial morphotypes, respectively. The morphotypes are interconvertible and equipotent, as shown by the formation of well-differentiated organoids. Surprisingly, the proliferation of both morphotypes requires Lif-type Gp130/Stat3 signaling (autocrine in the absence of added Lif) and noncanonical Wnt signaling (autocrine). In addition, the epithelial version requires β-catenin for proliferation and morphology. Interestingly, the mesenchymal cells also express key epithelial markers, but those are improperly structured and/or not functional, indicating a primed state. These results provide an improved platform for studying the proliferation and plasticity of the early ExEn, which occurs in mesenchymal and epithelial forms in vivo.

Controlling and mitigating infectious diseases caused by multiple pathogens or pathogens with several subtypes require multiplex nucleic acid detection platforms that can detect several target genes rapidly, specifically, sensitively, and simultaneously. Here, we develop a detection platform, termed Multiplex Assay of RPA and Collateral Effect of Cas12a-based System (MARPLES), based on multiplex nucleic acid amplification and Cas12a ssDNase activation to diagnose these diseases and identify their pathogens. We use the clinical specimens of hand, foot, and mouth disease (HFMD) and influenza A to evaluate the feasibility of MARPLES in diagnosing the disease and identifying the pathogen, respectively, and find that MARPLES can accurately diagnose the HFMD associated with enterovirus 71, coxsackievirus A16 (CVA16), CVA6, or CVA10 and identify the exact types of H1N1 and H3N2 in an hour, showing high sensitivity and specificity and 100% predictive agreement with qRT-PCR. Collectively, our findings demonstrate that MARPLES is a promising multiplex nucleic acid detection platform for disease diagnosis and pathogen identification.

Background: Cerebrovascular diseases are associated with high incidence of health care-associated infections (HAIs) and poor prognosis in elderly patients. This study aimed to investigate the incidence and clinical characteristics of HAIs in elderly patients with cerebrovascular disease in the intensive care unit (ICU)., Methods: Patients admitted with cerebrovascular disease, aged ≥65 years, were included. The clinical data of the patients were retrospectively analyzed to determine the risk factors, infection type, distribution, and pathogenic characteristics of HAIs in the context of cerebrovascular diseases., Results: Out of 381 ICU inpatients monitored, 79 (20.73%) developed HAIs. Risk analysis revealed number of ventilator days as significant risk factors for HAIs in elderly patients with cerebrovascular diseases in the comprehensive ICU. In the HAI group, 56 patients (70.89%) had respiratory tract infection (RTI). Sixty-five patients (82.28%) were infected with Gram-negative bacteria (GNB), and 42 (53.16%) with multi-drug-resistant organism (MDRO). The length of hospitalization days, ventilator days, and overall hospitalization costs were higher in the HAI group than in the non-HAI group (P < 0.05), but there was no significant difference between groups in the treatment outcome of patients. Patients with MDRO infection had longer duration and higher cost of hospitalization than those infected with non-MDRO (P < 0.05), but there was no significant difference between the groups in the treatment outcome of patients., Conclusions: HAIs occurred mostly due to RTI and GNB infection. The hospitalization cost and duration, as well as the length of ventilator days, were higher for cerebrovascular patients with HAIs than for non-HAIs patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Blueberry juice has been found to undergo severe browning after treatment and cold storage, such as processing by high hydrostatic pressure (HHP) at 550 MPa/10 min/25 °C followed storage at 4 °C for 4 days. This browning may be due to the degradation of anthocyanin (AC) in the berries. Therefore, in this study, gallic acid (GA), ferulic acid (FA), ascorbic acid (VC), citric acid (CA), tea polyphenol (TP) and α-tocopherol (VE) were compared to determine their ability to improve the stability of the AC in HHP-treated blueberry juice. The juice was combined with the six abovementioned antioxidants at different concentrations, then treated by HHP at 550 MPa/10 min/25 °C and stored at 4 °C for 20 days. Thereafter, the pH levels, degrees °Brix, color parameters, total AC content and polyphenol oxidase (PPO) activity of the blueberry juice blend were measured and compared. Gallic acid at 2 g/L was found to be the most effective antioxidant to protect against AC degradation. After storage at 4 °C for 20 days, the AC content of the juice with no added antioxidants had decreased by 62.27% with a PPO relative activity of 50.78%, while the AC content of juice supplemented with 2 g/L GA had decreased by 13.42% with a PPO relative activity of 28.13%. The results of this study, thus, suggest that GA can stabilize the structure of AC in blueberry juice and reduce PPO activity, which may be beneficial in guiding the production of blueberry juice with high AC retention.

Hematopoietic stem cell (HSC) transplantation provides an effective platform for the treatment of hematological disorders. However, the donor shortage of HSCs and immune responses severely restrict the clinical applications of HSCs. Compared to allogeneic transplantation, autogenous transplantation poses less risk to the immune system, but the problem associated with insufficient HSCs remains a substantial challenge. A significant strategy for obtaining sufficient HSCs is to promote the expansion of HSCs. In vivo , a bone marrow microenvironment supports the survival and hematopoiesis of HSCs. Therefore, it is crucial to establish a platform that mimics the features of a bone marrow microenvironment for the in vitro expansion of HSCs. Three-dimensional (3D) scaffolds have emerged as the most powerful tools to mimic cellular microenvironments for the growth and proliferation of stem cells. Biomedical polymers have been widely utilized as cell scaffolds due to their advantageous features including favorable biocompatibility, biodegradability, as well as adjustable physical and chemical properties. This review focuses on recent advances in the study of biomedical polymer scaffolds that mimic bone marrow microenvironments for the in vitro expansion of HSCs. Bone marrow transplantation and microenvironments are first introduced. Then, biomedical polymer scaffolds for the expansion of HSCs and future prospects are summarized and discussed.

CD2 is a costimulatory protein expressed in all mature T/NK-cells, in particular memory T-cells. CD58 (or LFA-3) is the receptor for CD2 and is ubiquitously expressed. CD2-CD58 interaction has key functions in T-cell activation and organization of the immunological synapse between T- and antigen-presenting cells. Cancer cells have developed multiple mechanisms to evade immune surveillance. Loss of CD58 expression is one frequently reported in diffuse large B-cell lymphomas (DLBCL). On the other hand, in non-hematological neoplasms, tumor infiltrating lymphocytes (TILs) with reduced expression of CD2 have been associated with defective cytotoxicity and T-cell exhaustion. Here, we reported a case of DLBCL involving the jejunal mucosa associated with a rim of cytotoxic reactive T-cells with features of immune evasion (CD2- and TCR-) and T-cell exhaustion (PD1 + high). This case likely exemplifies a previously unrecognized immune evasion mechanism in lymphoma involving a decreased CD2 expression in the lymphoma-associated T-cells., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) with unusual features, including some that can overlap morphologically with classic Hodgkin lymphoma (CHL), have been described. Herein, we describe 12 cases of NLPHL with fibrous bands and capsular fibrosis resembling, in part, nodular sclerosis (NS) CHL. Seven of 12 cases harbored Reed-Sternberg-like cells, further suggestive of CHL, but all cases lacked associated eosinophils and/or plasma cells in the background. In this cohort, all cases had areas of so-called pattern D (nodular T-cell rich) as a sole component in 7 (58%) cases or as a hybrid pattern along with pattern E (diffuse T-cell/histiocyte-rich) in 5 (42%) cases. The immunophenotype of the large neoplastic cells in these cases supported their being lymphocyte predominant cells of NLPHL, positive for CD20, CD79a, and OCT2, and negative for CD15 and CD30. However, PAX5 was weak in 9 of 11 cases similar to Hodgkin/Reed-Sternberg cells in CHL. We conclude that some cases of NLPHL are associated with fibrous bands and capsular fibrosis and resemble, in part, NS CHL. In our experience, NLPHL with NS-like features occurs in 10% to 15% of cases of NLPHL and is associated with a variant pattern (D and/or E). In addition, all patients in this cohort were not treated before biopsy, suggesting that the prominent sclerosis in these cases is inherent to disease biology. Recognition of NLPHL with NS-like features further expands the morphologic spectrum of NLPHL and helps avoid potential misdiagnosis as CHL., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

T- lymphoblastic leukemia/lymphoma (T-LL) is an aggressive malignancy of immature T-cells with poor overall survival (OS) and in need of new therapies. LIM-domain only 2 (LMO2) is a critical regulator of hematopoietic cell development that can be overexpressed in T-LL due to chromosomal abnormalities. Deregulated LMO2 expression contributes to T-LL development by inducing block of T-cell differentiation and continuous thymocyte self-renewal. However, LMO2 expression and its biologic significance in T-LL remain largely unknown. We analyzed LMO2 expression in 100 initial and follow-up biopsies of T-LL from 67 patients, including 31 (46%) early precursor T-cell (ETP)-ALL, 26 (39%) cortical and 10 (15%) medullary type. LMO2 expression was present in 50 (74.6%) initial biopsies with an average of 87% positive tumor cells (range 30-100%). LMO2 expression in ETP, medullary and cortical T-LLs was not statistically different. In patients with biopsies after initial therapy, LMO2 expression was stable. LMO2 expression was associated with longer OS (p = 0.048) regardless of T-lymphoblast stage or other clinicopathologic features. These findings indicate that LMO2 is a promising new prognostic marker that could predict patients' outcomes and potentially be targeted for novel chemotherapy, i.e. PARP1/2 inhibitors, which have been shown to enhance chemotherapy sensitivity in LMO2 expressing diffuse large B cell lymphoma (DLBCL) tumors by decreasing DNA repair efficiency., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Competing Interests: The authors declare that they have no conflict of interest.

Epigenetic abnormalities in DNA hydroxymethylation (5hmC) have been detected in patients with myeloid neoplasms, suggesting that 5hmC might act as a valuable epigenetic mark to reflect the disease status of myeloid neoplasms. Here, we report systematic genome-wide mapping of the DNA hydroxymethylomes in over 70 patients with myeloid neoplasms. Our integrative analysis leads to the identification of distinct 5hmC signatures that can sensitively discriminate patients from healthy individuals. At the molecular level, we unveiled dynamic 5hmC changes within key transcription factor (e.g., the CEBP family) binding motifs that are essential for hematopoiesis and myeloid lineage specification. 5hmC redistribution was found to alter the genome-wide binding of CEBP-α, thereby reprogramming transcriptional outputs to affect leukemia cell survival and stemness. Taken together, we provide a comprehensive 5hmC atlas representative of myeloid neoplasms, which sets the stage for future exploration on the epigenetic etiology of hematological malignancies. Mechanistically, our study further furnishes important insights into how abnormal 5hmC distribution in patients directly interrupts the binding of transcription factors to reshape transcriptional landscapes and aggravate leukemogenesis., (© 2022. The Author(s).)

Background: Acute myeloid leukemia (AML) with KMT2A (MLL) rearrangement is known for monocytic or myelomonocytic differentiation, but the full immunophenotypic spectrum and dynamic changes of the immunophenotype in this genetically defined disease have not been systematically studied., Methods: We reviewed the immunophenotype, karyotype, and mutations at the time of initial diagnosis and relapse of adults with AML with KMT2A rearrangement in our institution between 2007 and 2020., Results: We identified 102 patients: 44 men and 58 women with a median age of 52 years (range, 18-87). Forty-three patients were considered to be therapy-related. Twenty-four out of 64 patients relapsed from complete remission after induction therapy, 34 had persistent/progressive disease, and 58 patients died with a median overall survival of 17 months. We detected five immunophenotypes: immature monocytic (38%); myelomonocytic (22%); myeloblastic (22%); mature monocytic (10%); and acute promyelocytic (APL)-like (8%). By chromosomal breakpoints, we presumed 11 different partners; t(9;11) (p22;q23)/MLLT3-KMT2A was the most common rearrangement (n = 56, 55%), followed by t(6;11) (q27;q23)/AFDN-KMT2A (n = 13,13%). Patients with t(6;11) (q27;q23)/AFDN-KMT2A preferentially showed a myeloblastic phenotype (p = 0.026). Mutations were detected in 39/64 (61%) cases, and RAS pathway (NRAS/KRAS/PTPN11) was involved in 26/64 (41%) cases. None of the APL-like cases had mutations detected. At the time of disease relapse, 10/24 (42%) showed major immunophenotypic change, and 7/10 cases gained additional cytogenetic and/or molecular alterations., Conclusion: The immunophenotype of AML with KMT2A rearrangement is more diverse than previously recognized, with a substantial subset showing no evidence of monocytic differentiation. Major immunophenotype change is common at the time of relapse., (© 2021 International Clinical Cytometry Society.)

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with myelofibrosis (MF). Bone marrow (BM) morphologic evaluation of myelofibrosis following allo-HSCT is known to be challenging in this context because resolution of morphologic changes is a gradual process., Patients and Methods: We compared BM samples of patients with myelofibrosis who underwent first allo-HSCT and achieved molecular remission by day 100 with BM samples of patients who continued to have persistent molecular evidence of disease following allo-HSCT., Results: The study group included 29 patients: 17 primary MF, 7 post-polycythemia vera (PV) MF, and 5 post-essential thrombocythemia (ET) MF. In this cohort there were 18 JAK2 p.V617F, 8 CALR; 1 MPL, and 2 patients had concurrent JAK2 p.V617F and MPL mutations. The control group included 5 patients with primary MF, one with post-PV MF, one with post-ET MF (5 JAK2 p.V617F; 2 CALR). Following allo-HSCT, both groups showed reduction in BM cellularity and number of megakaryocytes. The study cohort also less commonly had dense megakaryocyte clusters and endosteal located megakaryocytes and showed less fibrosis. There was no statistical difference in BM cellularity, presence of erythroid islands, degree of osteosclerosis, or megakaryocyte number, size, nuclear lobation, presence of clusters or intrasinusoidal location., Conclusions: Following allo-HSCT at 100 days, morphologic evaluation of BM in patients with MF cannot reliably predict persistence versus clearance of molecular evidence of MF. Disappearance of BM MF, dense megakaryocyte clusters, and endosteal localization of megakaryocytes are suggestive of disease response., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Light-chain restricted hematogones (LCR HGs) detected by flow cytometry analysis can mimic bone marrow involvement by B-cell lymphoma. This phenomenon can present a diagnostic pitfall and negatively impact patient management, as misinterpretation may upgrade disease stage. In this study, we characterized the immunophenotype of LCR HGs with an aim to differentiate them from B-cell lymphoma. We analyzed 24 patients with LCR HGs, 12 (50 %) were kappa light chain restricted and 12 (50 %) were lambda light chain restricted. LCR HGs account for 51 % (range, 1.5%-99%) of B cells, and 0.5 % (range, 0.1%-3.7%) of total cells. In 15 patients in whom multiple specimens were analyzed, 10 (67 %) showed persistent LCR HGs in more than 1 specimen, and the duration of the light chain restriction ranged from 4 months to 2 years. Among 24 patients, 4 (16.6 %) cases were concurrently involved by B-cell lymphoma/myeloma in addition to LCR HGs. With the exception of light chain restriction, LCR HGs showed a similar immunophenotype as normal HGs and had a distinct location on the CD45/Side Scatter (SSC) plot. They were also consistently positive for CD10, CD19, CD38 (bright), CD43, and CD200. CD20 expression showed a spectrum from dim/negative to positive., (Copyright © 2021. Published by Elsevier Ltd.)

Background: The study aimed to characterize the prevalence of alcohol consumption and further investigate the relationship between alcohol consumption and type 2 diabetes mellitus (T2DM)., Methods: We studied 39,259 participants aged 18 to 79 years of the Henan Rural Cohort study. The associations between alcohol consumption and T2DM were examined using the logistic regression models and restricted cubic spline., Results: For men, alcohol abstinence was associated with an increased risk of T2DM (1.491(1.265, 1.758)), whereas current drinkers were not associated with T2DM (1.03(0.91, 1.15)). Further analysis of alcohol drinkers revealed that only high-risk drinkers of WHO drinking risk levels increased the risk of T2DM (1.289(1.061,1.566)) compared to never drinkers. The risk of T2DM increased as the age of starting to consume alcohol decreased and as the number of years of consuming alcohol and the alcohol intake increased only in men. We further found that the risk of T2DM decreased as the number of years of abstinence increases and no association between alcohol abstinence and T2DM was found after more than 10 years of abstinence among men., Conclusions: Our results suggested that reducing the amount of alcohol consumed and adhering to abstinence from alcohol consumption are beneficial in reducing the risk of T2DM., Trial Registration: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-07-06. http://www.chictr.org.cn/showproj.aspx?proj=11375., (© 2021. The Author(s).)

Corolla closure protects pollen from high-temperature stress during pollen germination and fertilization in the ornamental plant morning glory ( Ipomoea purpurea ). However, the morphological nature of this process and the molecular events underpinning it remain largely unclear. Here, we examined the cellular and gene expression changes that occur during corolla closure in the I . purpurea . We divided the corolla closure process into eight stages (S0-S7) based on corolla morphology. During flower opening, bulliform cells appear papillate, with pigments in the adaxial epidermis of the corolla. These cells have distinct morphology from the smaller, flat cells in the abaxial epidermis in the corolla limb and intermediate of the corolla. During corolla closure, the bulliform cells of the adaxial epidermis severely collapse compared to cells on the abaxial side. Analysis of transparent tissue and cross sections revealed that acuminate veins in the corolla are composed of spiral vessels that begin to curve during corolla closure. When the acuminate veins were compromised, the corolla failed to close normally. We performed transcriptome analysis to obtain a time-course profile of gene expression during the process from the open corolla stage (S0) to semi-closure (S3). Genes that were upregulated from S0 to S1 were enriched in the polysaccharide degradation pathway, which positively regulates cell wall reorganization. Senescence-related transcription factor genes were expressed beginning at S1, leading to the activation of downstream autophagy-related genes at S2. Genes associated with peroxisomes and ubiquitin-mediated proteolysis were upregulated at S3 to enhance reactive oxygen species scavenging and protein degradation. Therefore, bulliform cells and acuminate veins play essential roles in corolla closure. Our findings provide a global understanding of the gene regulatory processes that occur during corolla closure in I. purpurea ., 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 Zhang, Sun, Wang, Guo, Sun, Gui, Li, Wang and Zhang.)

Plants inevitably receive harmful UV-B radiation when exposed to solar energy, so they have developed a variety of strategies to protect against UV-B radiation damage during long-term evolution. In this study, Zebrina pendulaSchnizl. was used to investigate the plant defence against UV-B radiation because of its strong adaptability to sunlight changes, and the colour of its leaves changes significantly under different sunlight intensities. The experiment was carried out to study the changes of Z. pendula leaves under three light conditions: artificial daylight (control check); shading 50%; and artificial daylight + UV-B, aiming to explore the mechanism of defence against UV-B radiation by observing changes in leaf morphological structure, anthocyanin content and distribution. Results showed that the single leaf area increased but leaves became thinner, and the anthocyanin content in the epidermal cells decreased under 50% shading. In contrast, under daylight + UV-B, the single leaf area decreased but thickness increased (mainly due to the increase of the thickness of the upper epidermis and the palisade tissue), the trichomes increased. In addition, the anthocyanin content in the epidermal cells and phenylalanine ammonia-lyase (PAL) activity increased, and the leaf colour became redder, also, the photosynthetic pigment content in mesophyll cells and the biomass per unit volume increased significantly under daylight + UV-B. Thus, when UV-B radiation was enhanced, Z. pendula leaves reduced the exposure to UV-B radiation by reducing the area, and reflect some UV-B radiation by growing trichomes. The UV-B transmittance was effectively reduced by increasing the single leaf thickness and anthocyanin content to block or absorb partial UV-B. Through the above comprehensive defence strategies, Z. pendula effectively avoided the damage of UV-B radiation to mesophyll tissue.

Background: Previous reports about health-related quality of life (HRQoL) of type 2 diabetes mellitus (T2DM) concentrated on general patients rather than patients in rural areas with poor infrastructure and limited resources. Thus, the aims of this study were to evaluate the HRQoL of diabetics in the countryside and explore its influencing factors., Methods: A total of 23 053 participants aged from 18 to 79 years were drawn from the Henan Rural Cohort Study for this cross-sectional study. The HRQoL of participants were assessed by utility index and VAS-score of European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) instrument. Binary logistic regression, generalized linear and tobit regression models were used to estimate the potential influencing factors on HRQoL., Results: This study (23 053 participants) included 2231 T2DM patients with a crude prevalence of 9.68%. The utility index and VAS-score in health group were 0.96 ± 0.10 and 78.85 ± 14.53, while in T2DM group were 0.93 ± 0.15 and 74.09 ± 16.09, respectively. In total, most diabetics reported problem about pain/discomfort dimension. Being old, poverty, low physical activity, and with comorbidities was negatively related to HRQoL of diabetics, while high educational level was positively related to HRQoL., Conclusion: HRQoL of rural T2DM patients depended on several sociodemographic factors. More attention should be paid to diabetics with poor socioeconomic status in rural areas., Clinical Trial Registration: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699) http://www.chictr.org.cn/showproj.aspx?proj=11375., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: The study aimed to investigate the independent and combined effects of midpoint of sleep and night sleep duration on type 2 diabetes mellitus (T2DM) in areas with limited resources., Methods: A total of 37,276 participants (14,456 men and 22,820 women) were derived from the Henan Rural Cohort Study. Sleep information was assessed based on the Pittsburgh Sleep Quality Index. Logistic regression models and restricted cubic splines were used to estimate the relationship of the midpoint of sleep and night sleep duration with T2DM., Results: Of the 37,276 included participants, 3580 subjects suffered from T2DM. The mean midpoint of sleep among the Early, Intermediate and Late groups were 1:05 AM ±23 min, 1:56 AM ±14 min, and 2:57 AM ±34 min, respectively. Compared to the Intermediate group, adjusted odds ratios (ORs) and 95% confidence interval (CI) of T2DM were 1.13 (1.04-1.22) and 1.14 (1.03-1.26) in the Early group and the Late group. Adjusted OR (95% CI) for T2DM compared with the reference (7- h) was 1.28 (1.08-1.51) for longer (≥ 10 h) night sleep duration. The combination of late midpoint of sleep and night sleep duration (≥ 9 h) increased 38% (95% CI 10-74%) prevalence of T2DM. These associations were more obvious in women than men., Conclusions: Late and early midpoint of sleep and long night sleep duration were all associated with higher prevalence of T2DM. Meanwhile, midpoint of sleep and night sleep duration might have combined effects on the prevalence of T2DM, which provided potential health implications for T2DM prevention, especially in rural women., Trial Registration: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699 ). Date of registration: 2015-07-06.

Aggressive B-cell lymphomas are currently classified based in part upon the presence or absence of translocations involving BCL2, BCL6, and MYC. Most clinical laboratories employ fluorescence in situ hybridization (FISH) analysis for the detection of these rearrangements. The potential role of RNA-based sequencing approaches in the evaluation of malignant lymphoma is currently unclear. In this study, we performed RNA sequencing (RNAseq) in 37 cases of aggressive B-cell lymphomas using a commercially available next generation sequencing assay and compared results to previously performed FISH studies. RNAseq detected 1/7 MYC (14%), 3/8 BCL2 (38%) and 4/8 BCL6 (50%) translocations identified by FISH. RNAseq also detected 1 MYC/IGH fusion in a case not initially tested by FISH due to low MYC protein expression and 2 BCL6 translocations that were not detected by FISH. RNAseq identified the partner gene in each detected rearrangement, including a novel EIF4G1-BCL6 rearrangement. In summary, RNAseq complements FISH for the detection of rearrangements of BCL2, BCL6 and MYC in the evaluation and classification of aggressive B-cell lymphomas by detecting rearrangements that may be cryptic by FISH methods and by identifying the rearrangement partner genes. Detection of these clinically important translocations may be optimized by combined use of FISH and RNAseq., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Traditionally cultured monolayers of primary human hepatocytes (PHHs) deteriorate within days and thereby become unsuitable for drug-related studies. PHH spheroids (3D PHHs) maintain liver functions for weeks, but are considerably more demanding. Recently, a chemical-based approach (5C PHHs) succeeded in long-term culture of hepatocyte monolayers, but it remains unclear whether the drug-related functions are preserved. To clarify this, we compared the 5C and 3D PHHs in terms of gene expression analysis, proteomic analysis, functionality (basal and induced activities of representative CYP450 enzymes and urea and albumin secretions), survival in culture, and sensitivity to representative drugs. In all comparisons, which spanned culture durations of up to 4 weeks, the 5C PHHs performed at least as well as the 3D PHHs. Hence, the novel 5C PHH monolayer format combines the convenience of the traditional monolayer format with the functionality and maintainability of the spheroid format. Our results suggest that 5C PHH monolayers can be used more conveniently and efficiently for high-throughput drug screening, preclinical drug safety evaluations, and mechanistic studies., (© 2021 Federation of American Societies for Experimental Biology.)

Introduction: We aimed to explore the association between night sleep duration and ideal cardiovascular health (ICH) among Chinese rural population. Methods: In all, 35,094 participants were included from the Henan Rural Cohort study. Information on sleep was collected using the Pittsburgh Sleep Quality Index. The ICH scores were evaluated. The associations between night sleep duration and ICH were examined using both linear regression and logistic regression models. Results: The mean night sleep duration for all participants was 7.75 ± 1.28 h. Compared with those with night sleep duration of 7 to <9 h by using linear regression model, a significant decrease in ICH scores was observed for participants with shorter [-0.077 (-0.131, -0.024)] and longer [-0.079 (-0.121, -0.036)] night sleep duration. Compared with 7 to <9 h, longer sleep duration [0.919 (0.851, 0.992)] were associated with decreased odds of ideal CVH. Conclusions: Shorter and longer night sleep duration are negatively associated with ICH among rural population. This suggests that it may be beneficial to include night sleep duration assessment in cardiovascular risk screening., 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 Wu, Liu, Liao, Kang, Sang, Abdulai, Zhai, Wang, Wang and Li.)

A novel dual-emission ratiometric fluorescent sensor (CDs@Eu-MOFs) has been synthesized successfully by encapsulating water-soluble fluorescent CDs into the chambers of Eu-MOFs via a simple one-pot hydrothermal method, which can be used for the detection of Hg 2+ in environmental water samples. The synthesized CDs@Eu-MOFs inherited simultaneously the excellent luminescence performance of Eu 3+ and CDs and exhibited good structural and fluorescence stability in aqueous solution. The presence of Hg 2+ changed the fluorescence intensity of CDs, while the fluorescence intensity of Eu-MOFs hardly changed, which could be used as the recognition part and the reference part respectively to construct the ratiometric fluorescence sensor. The obtained Hg 2+ fluorescent probe showed a wide linear range (0-300 μM) and a low detection limit (0.12 nM). The developed method can be used as a multi-functional fluorescent sensor with high sensitivity and good selectivity for the determination of Hg 2+ in actual water samples., Competing Interests: Declaration of competing interest About this paper, no any interest conflict exists., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: To explore potential value of guard-wire technology during percutaneous coronary intervention (PCI) in patients with ostial coronary lesions., Methods: Patients, who underwent PCI, were collected between October 2011 and March 2017. Of the 141 patients, 63 (44.7%) have ostial lesions, and 78 (55.3%) have distal bifurcation sites. They were divided into group A (n = 71) and group B (n = 70). Group A received PCI after guard-wire technology. Group B were given balloon dilation and stent after placing guide wire through target lesion vessel. X-ray exposure time, contrast agent dosage, total PCI duration, pressure incarceration times, cases of malignant arrhythmia and cases of failed PCI of all patients were analyzed, respectively., Results: The general clinical characteristics includes patients age, sex ratio, the proportion of complications, smoking ratio and left ventricular ejection fraction of both groups was not significantly different. X-ray exposure time, contrast agent dosage, PCI total time, stent positioning time, pressure infestation frequency, arrhythmia frequency and complication number of group B were higher than those of group A. There is no case of malignant arrhythmia and case of failed PCI in group A, while there were five malignant arrhythmia and four failed PCI in group B. Contrast agent dosage and cases of failed PCI increased in group B compared with group A., Conclusion: The guard wire technology is safer and more feasible to patients with ostial coronary lesions who underwent PCI.

A novel composite (CDs@ZIF-8) based on carbon dots (CDs) and zeolitic imidazolate framework (ZIF-8) was successfully synthesized by encapsulating CDs into the pores of ZIF-8 through a simple one-pot solvothermal method. The as-synthesized CDs@ZIF-8 inherited simultaneously the strong adsorption capacity of ZIF-8 and the excellent optical properties of CDs. The composite exhibited excellent dispersibility and high structural and fluorescence stability in aqueous solution, which could be employed as an excellent turn-off mode fluorescent probe to detect Cu 2+ . The large specific surface area and strong adsorption properties of ZIF-8 enabled the resultant composite to effectively enrich Cu 2+ for further improving the analytical sensitivity. The possible fluorescence quenching mechanism has also been discussed in detail and it was found that the effective fluorescence quenching of Cu 2+ to CDs@ZIF-8 could be attributed to the strong ability of Cu 2+ to combine with the carboxyl group or amino group on the CD surface and the strong adsorption capacity of ZIF-8; their synergistic effect resulted in effective fluorescence quenching.

The objective of this study is to investigate the effects of high pressure processing (HPP) on the quality of mango smoothies and the inactivation of microorganisms therein, with heat treatments used as the control. Comparative analysis was conducted on the microbiological changes in the mango smoothies subjected to HPP at 400-600 MPa for 0-15 min. The total plate count (TPC) and the yeast and mold (YM) counts were found to be significantly inactivated through increases in the pressure and treatment time ( p < 0.05). Conditions of 90 °C/20 min (HT), 500 MPa/8 min (HPP-500) and 600 MPa/5 min (HPP-600) were, thus, selected as the subsequent treatment for a storage study at 4 °C for 15 days, since these conditions had similar inactivation effects on TPC and YM. After 15 days of storage, the TPC was found to have increased by 3.87, 3.54 and 3.36 log 10 cycles in the mango smoothies treated by HT, HPP-500 and HPP-600, respectively, while the YM counts remained at less than 1 log 10 cycle in all samples. During storage, compared to the HT and HPP-600 samples, both the color and viscosity at 100 s -1 of samples treated by HPP-500 were found to be better maintained. Carotene content was better retained in storage after the HPP process than after the HT process. However, the different treatments had no effect on the pH nor on the total soluble solids (TSS) in the samples. The study ascertained that HPP-500 is able to ensure both the microbial safety and the quality of mango smoothies more effectively than HT and HPP-600., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This multi-institutional study retrospectively evaluated clinicopathologic and genetic characteristics in 351 patients with core-binding-factor acute myeloid leukemia (CBF-AML), comprising 69 therapy-related (t-CBF-AML) and 282 de novo cases. The T-CBF-AML patients were older, had lower WBC counts, and slightly higher hemoglobin than patients with de novo disease. Secondary cytogenetic abnormalities were more frequent in patients with de novo disease than t-CBF-AML (57.1% vs 41.1%, P = .026). Patients with secondary cytogenetic abnormalities had longer overall survival (OS) than those without abnormalities (median 190 vs 87 months, P = .021); trisomy 8, trisomy 22, and loss of the X or Y chromosome were associated with longer OS. In the 165 cases performed of targeted gene sequencing, pathogenic mutations were detected in 75.7% of cases, and were more frequent in de novo than in therapy-related disease (P = .013). Mutations were found in N/KRAS (37.0%), FLT3 (27.8%), KIT (17.2%), TET2 (4.9%), and ASXL1 (3.9%). The TET2 mutations were associated with shorter OS (P = .012) while N/KRAS mutation was associated with longer OS in t(8;21) AML patients (P = .001). The KIT mutation did not show prognostic significance in this cohort. Although they received similar therapy, t-CBF-AML patients had shorter OS than de novo patients (median 69 vs 190 months, P = .038). In multivariate analysis of all patients, older age and absence of any secondary cytogenetic abnormalities were significant predictors of shorter OS. Among the t-CBF-AML subset, age and hemoglobin were significant on multivariate analysis. This study demonstrated that although de novo and t-CBF-AML patients share many features, t-CBF-AML patients have worse clinical outcome than de novo patients., (© 2020 Wiley Periodicals, Inc.)

An Eu(III)-functionalized strontium-organic framework (Eu 3+ @Sr-MOF) was synthesized by encapsulating Eu 3+ ions into the pores of Sr-MOF via postsynthetic modification (PSM) and fully characterized by XRD, SEM, EDS, FTIR, and TGA. The luminescent properties of Eu 3+ @Sr-MOF were measured and investigated in detail, which demonstrated that Eu 3+ @Sr-MOF not only possessed excellent water and chemical stabilities in a wide pH range (5-10) but also displayed red luminescence with excitation/emission maxima at 332/617 nm. The Eu 3+ @Sr-MOF can be considered as a highly selective and sensitive recyclable luminescence probe for sensing Cr(III) and Cr(VI) based on strong luminescence quenching effects; it can be recycled at least five times. The luminescence probe for Cr 3+ , CrO 4 2- , and Cr 2 O 7 2- shows low detection limits (0.15 μM, 0.17 μM, and 0.13 μM, respectively), relatively broad linear ranges (0.6-150 μM, 0.1-200 μM and 0.4-180 μM, respectively), and high quenching constants K SV . The signals can be observed by the naked eye under UV light of 365 nm. The method was applied to the determination of total Cr in environmental water samples. Graphical abstract.

The brittle failure of Chengkou shale occurs throughout the exploration and development processes of hydrocarbons. To investigate the failure mechanisms of Chengkou shale and analyze the associated mechanical behavior such as crack initiation, propagation, and coalescence at different stress levels, a series of laboratory experiments were conducted on servo-controlled triaxial cells equipped with ultrasound monitoring. The experimental results show that key mechanical parameters such as peak stress σ p , stress onset of dilation σ ci , and strain at peak stress ε p exhibit nearly linear relationships at various confining pressures. In rock bodies, the wave velocity evolution at different stress levels very consistently reproduces the shape of stress-strain curves, while shear wave velocity v s is more sensitive to crack damage than compressional wave velocity v p . Furthermore, the Hoek-Brown failure criterion has an advantage over the Mohr-Coulomb fracture criterion due to the former's higher correlation coefficient r 2 . The wing crack damage models with sandwiched multilayers help explain the mixed tensile and shear failure mechanisms of Chengkou shale. The experimental results provide significant guidance for optimizing the design of drilling and well completion jobs, especially hydraulic fracturing operations, both in Chengkou shale and in other brittle shales around the world., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

In this paper, the high-temperature/high-pressure triaxial testing system of rocks is used to study the effect of spontaneous fluid imbibition on the formation mechanism of fracture networks, by means of acoustic emission (AE) monitoring and ultrasound measurement. After the water-shale interaction, the rock mechanical parameters such as rock strength, elastic modulus, cohesion, and internal friction angle of shales significantly decrease as the imbibition time increases, indicating that the fluid has a strong influence on the mechanical properties of brittle shales. The stress-strain curves of the wet and dry shales and their AE characteristics are quite different: (i) the stress-strain curve of wet shale samples shows multiple fluctuations before macroscopic failure, and its cumulative AE number curve presents a step-like jump many times that corresponds to the local microcracking; (ii) the stress-strain curve of dry shale samples mainly shows the characteristic of linear elastic deformation during early loading, which has less AE event number, and the step-like jump is not observed in all the AE curves. The dry shale only has a large number of AE events until it is close to macroscopic failure. Nuclear magnetic resonance, mineral composition, and microstructure analysis show that Chengkou shale generally develops micro-nanoscale pores with a small pore throat, and thus strong capillary spontaneous absorption occurs. The shale-water interaction includes both chemical and physical effects, which affect the key parameters such as acoustic velocity, frictional force on the surfaces of artificial fracture, fracability, and other mechanical properties. This paper provides new insights to the investigation on the formation mechanism of artificial fracture networks in brittle shales., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Background: Circular RNAs (circRNAs) have been shown to play a crucial role in tumorigenesis. In this study, we investigated the function of hsa&#95;circ&#95;0137008 and its underlying molecular mechanism in colorectal cancer (CRC)., Methods: Gene expression was conducted by quantitative real-time PCR or western blot. Functional experiments were performed by cell count kit-8, colony formation assay, wound healing, and transwell assays. Luciferase reporter assay and RNA pull-down assay were performed to investigate the molecular mechanism of hsa&#95;circ&#95;0137008 in CRC. In addition, the xenograft tumor model was applied to determine the role of hsa&#95;circ&#95;0137008 in vivo., Results: Downregulation of hsa&#95;circ&#95;0137008 was observed in CRC tissues and cell lines. Functionally, overexpression of hsa&#95;circ&#95;0137008 inhibited the proliferation of CRC cells, as indicated by the inhibition of proliferative protein expression (Ki67 and PCNA), reduced cell viability and colony formation ability. Upregulation of hsa&#95;circ&#95;0137008 suppressed the migration, invasion, and epithelial to mesenchymal transition (EMT) of CRC cells. Mechanically, hsa&#95;circ&#95;0137008 negatively regulated the expression of microRNA-338-5p (miR-338-5p). Furthermore, hsa&#95;circ&#95;0137008 abated the miR-338-5p mediated promotion on CRC cell progression. Tumor suppressive function of hsa&#95;circ&#95;0137008 was validated in vivo., Conclusion: These findings highlighted the fact that overexpression of hsa&#95;circ&#95;0137008 inhibited the progression of CRC via sponging miR-338-5p, suggesting that hsa&#95;circ&#95;0137008/miR-338-5p axis is a principal regulator of CRC tumorigenesis., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Changes in the microbial, physicochemical, and sensory properties of blended strawberry-apple-lemon juice were investigated to comparatively assess the influence of three processing treatments, namely high hydrostatic pressure (HHP) (500 MPa/15 min/20 °C), ultrasound (US) (376 W/10 min/35 °C), and heat treatment (HT) (86 °C/1 min) over 12 days of storage at 4 °C. The results showed that the total aerobic bacteria (TAB) counts in the HHP-, US-, and HT-treated juice blends were less than 2 log 10 CFU/mL, the yeast and mold (Y & M) counts were less than 1.3 log 10 CFU/mL, and the coliforms most probable number (MPN/100 mL) was less than 3 after 10 days at 4 °C. Anthocyanins were maintained by HHP, but decreased by 16% and 12% after US and HT, respectively. Total phenols increased by 18% and 7% after HHP and US, respectively, while they were maintained by the HT. Furthermore, better maintenance of total phenols, total anthocyanins, ascorbic acid, antioxidant capacity, color, and sensory values were observed in the HHP-treated juice blend stored for 10 days at 4 °C, compared to both the US- and HT-treated samples. Therefore, HHP was proposed to be a better processing technology for juice blend.

The deafness-associated m.12201T>C mutation affects the A5-U68 base-pairing within the acceptor stem of mitochondrial tRNA His The primary defect in this mutation is an alteration in tRNA His aminoacylation. Here, we further investigate the molecular mechanism of the deafness-associated tRNA His 12201T>C mutation and test whether the overexpression of the human mitochondrial histidyl-tRNA synthetase gene ( HARS2 ) in cytoplasmic hybrid (cybrid) cells carrying the m.12201T>C mutation reverses mitochondrial dysfunctions. Using molecular dynamics simulations, we demonstrate that the m.12201T>C mutation perturbs the tRNA His structure and function, supported by decreased melting temperature, conformational changes, and instability of mutated tRNA. We show that the m.12201T>C mutation-induced alteration of aminoacylation tRNA His causes mitochondrial translational defects and respiratory deficiency. We found that the transfer of HARS2 into the cybrids carrying the m.12201T>C mutation raises the levels of aminoacylated tRNA His from 56.3 to 75.0% but does not change the aminoacylation of other tRNAs. Strikingly, HARS2 overexpression increased the steady-state levels of tRNA His and of noncognate tRNAs, including tRNA Ala , tRNA Gln , tRNA Glu , tRNA Leu(UUR) , tRNA Lys , and tRNA Met , in cells bearing the m.12201T>C mutation. This improved tRNA metabolism elevated the efficiency of mitochondrial translation, activities of oxidative phosphorylation complexes, and respiration capacity. Furthermore, HARS2 overexpression markedly increased mitochondrial ATP levels and membrane potential and reduced production of reactive oxygen species in cells carrying the m.12201T>C mutation. These results indicate that HARS2 overexpression corrects the mitochondrial dysfunction caused by the tRNA His mutation. These findings provide critical insights into the pathophysiology of mitochondrial disease and represent a step toward improved therapeutic interventions for mitochondrial disorders., (© 2020 Gong et al.)

Background/aims: miR-802 plays a key role in cancer progression and development. The purpose of this work is to investigate the functional role of miR-802 in laryngeal cancer and to elucidate the function of miR-802 and cAMP-regulated phosphoprotein 19 (ARPP19) on laryngeal cancer., Methods: RT-qPCR was applied to study the expression level of ARPP19 and miR-802 in the laryngeal carcinoma cell lines and tissues. CCK-8, colony formation, flow cytometry (FACS) assay were used to study the effect of ARPP19 and miR-802 on apoptosis, proliferation, and cell cycle of laryngeal carcinoma cells. Target gene prediction and luciferase reporter gene assay were applied to identify target gene of miR-802. The transcriptional mRNA and protein expression levels of ARPP19 were measured by RT-qPCR or Western blotting., Results: miR-802 was down-regulated in laryngeal carcinoma cell lines and tissues. Laryngeal cancer cells transfected by miR-802 mimic were significantly inhibited in the terms of cell colony formation and proliferation. Furthermore, miR-802 can inhibit the expression level of ARPP19 by directly targeting the 3' untranslated region (3'-UTR) of ARPP19. Overexpression of the ARPP19 gene can reverse the suppressive effect of miR-802 on laryngeal cancer cells., Conclusion: miR-802 can exert tumor suppressor effects in laryngeal carcinoma by targeting ARPP19, indicating that miR-802 protein may play a role of potential therapeutic target for clinical laryngeal cancer., Competing Interests: The authors declare that they have no competing interests in this work., (© 2020 Ye et al.)

An investigation was conducted into the utilization of treatments combining ultrasound and lysozyme (US + Lys) to deactivate Salmonella typhimurium (S. typhimurium) in the liquid whole egg (LWE). Furthermore, US + Lys and heat treatment (HT) with a similar microbial inactivation effect were comparatively evaluated by examining their impact on the quality attributes of LWE. The LWE was treated with US at 35-45 °C and 605-968 W/cm 2 for 5-35 min, and with HT at 58-64 °C for 3-4 min. Lysozyme (Lys) alone achieved a minimal degree of inactivation in S. typhimurium, while it was enhanced with the application of US alone when the treatment temperature, time, and energy were increased. Furthermore, US and US + Lys caused a reduction of 3.31 and 4.26 log 10 cycles in S. typhimurium, respectively at 968 W/cm 2 and 35 °C for 20 min, indicating a synergistic relationship between US and Lys for the effective inactivation of S. typhimurium. Similarly, HT and HT + Lys achieved a reduction of 4.10 and 4.75 log 10 cycles at 64 °C/3 min, respectively. The L* and b* values of the LWE following US and US + Lys application were significantly higher than untreated and heat-treated LWE, indicating that US treated LWE had a brighter and yellower appearance. The protein solubility (PS) slightly decreased after all treatments, while the pH increased. Furthermore, the foaming capacity (FC) and foam stability (FS) were decreased, revealing that LWE had a lower FC and unstable foam after all treatments. Therefore, US and US + Lys could increase the viscosity and gelation temperature (Tg) of LWE, indicating that LWE exhibited higher heat resistance after US treatment. These results indicated that US + Lys might be a promising pasteurization technology in the processing of LWE., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Acute lung injury (ALI) is characterized by acute lung inflammation and apoptosis of alveolar epithelial cells (AECs) with a high morbidity and mortality. Procyanidin B2 (PCB2) is a naturally occurring flavonoid with anti-inflammatory activity. Our previous study demonstrated that PCB2 inhibited NLRP3 inflammasome signaling and ameliorated paraquat-induced ALI in rat, indicating the protective role of PCB2. As lipopolysaccharide (LPS) induced acute cell injury and dysfunction, we continued to evaluate the protective effects of PCB2 using LPS-treated human AECs and lung fibroblasts (LFs) model. We tested the effects of PCB2 on cell permeability, viability, apoptosis, nuclear factor-kappaB (NF-κB) activation, NLRP3 inflammasome activation, and proinflammatory cytokines production in LPS-treated human AECs and LFs. PCB2 prevented LPS-induced cell apoptosis, and increased the cell viability in LPS-treated human AECs and LFs. PCB2 inhibited LPS-induced Bax and active caspase-3 expression, and promoted Bcl-2 expression. PCB2 prevented LPS-induced tumor necrosis factor-α, interleukin-1β expression, NF-κB activation, and NLRP3 inflammasome activation. PCB2 suppressed LPS-induced inflammation and apoptosis in human AECs and LFs by inhibiting NF-κB and NLRP3 inflammasome.

Background: Malignancy probability models for pulmonary nodules (PN) are most accurate when used within populations similar to those in which they were developed. Our goal was to develop a malignancy probability model that estimates the probability of malignancy for PNs considered high enough risk to recommend biopsy., Methods: This retrospective analysis included training and validation datasets of patients with PNs who had a histopathologic diagnosis of malignant or benign. Radiographic and clinical characteristics associated with lung cancer were collected. Univariate logistic regression was used to identify potential predictors. Stepdown selection and multivariate logistic regression were used to build several models, each differing according to available data., Results: Two hundred malignant nodules and 101 benign nodules were used to generate and internally validate eight models. Predictors of lung cancer used in the final models included age, smoking history, upper lobe location, solid and irregular/spiculated nodule edges, emphysema, fluorodeoxyglucose-PET avidity, and history of cancer other than lung. The concordance index (C-index) of the models ranged from 0.75 to 0.81. They were more accurate than the Mayo Clinic model (P < .05 for four of the models), and each had fair to excellent calibration. In an independent sample used for validation, the C-index for our model was 0.67 compared with 0.63 for the Mayo Clinic model. The ratio of malignant to benign nodules within each probability decile showed a greater potential to influence clinical decisions than the Mayo Clinic model., Conclusions: We developed eight models to help characterize PNs considered high enough risk by a clinician to recommend biopsy. These models may help to guide clinicians' decision-making and be used as a resource for patient communication., (Copyright © 2019. Published by Elsevier Inc.)

Background: Increasing evidence shows that long non-coding RNAs (lncRNAs) play a key role in the development of various cancers. Zinc finger antisense 1 (ZFAS1) is a novel lncRNA with previously demonstrated associations with several types of cancer. Here we examined the expression and potential function of the ZFAS1 in nasopharyngeal carcinoma (NPC)., Methods: We detected ZFAS1 expression in GSE12452, a human microarray dataset, and NPC cell lines. Small interfering RNA against ZFAS1 was used to elucidate the cellular functions of ZFAS1 using MTT, colony formation, cell cycle, cell apoptosis, transwell invasion and migration and western blot assays. An activator of the PI3K/AKT signaling pathway (740Y-P) was used to determine the contribution of PI3K/AKT., Results: ZFAS1 was significantly upregulated in NPC tissues and cell lines. Silencing ZFAS1 significantly inhibited cell proliferation and invasion, arrested cell cycle progression and promoted cell apoptosis, as well as reduced epithelial-mesenchymal transition. Moreover, 740Y-P could rescue the effects of ZFAS1 knockdown on proliferation, apoptosis and invasion in 5-8F cells., Conclusions: ZFAS1 might play an oncogenic role in NPC and facilitate cell proliferation and invasion via the PI3K/AKT signaling pathway in NPC cells.

Mammalian cells are surrounded by neighbouring cells and extracellular matrix (ECM), which provide cells with structural support and mechanical cues that influence diverse biological processes 1 . The Hippo pathway effectors YAP (also known as YAP1) and TAZ (also known as WWTR1) are regulated by mechanical cues and mediate cellular responses to ECM stiffness 2,3 . Here we identified the Ras-related GTPase RAP2 as a key intracellular signal transducer that relays ECM rigidity signals to control mechanosensitive cellular activities through YAP and TAZ. RAP2 is activated by low ECM stiffness, and deletion of RAP2 blocks the regulation of YAP and TAZ by stiffness signals and promotes aberrant cell growth. Mechanistically, matrix stiffness acts through phospholipase Cγ1 (PLCγ1) to influence levels of phosphatidylinositol 4,5-bisphosphate and phosphatidic acid, which activates RAP2 through PDZGEF1 and PDZGEF2 (also known as RAPGEF2 and RAPGEF6). At low stiffness, active RAP2 binds to and stimulates MAP4K4, MAP4K6, MAP4K7 and ARHGAP29, resulting in activation of LATS1 and LATS2 and inhibition of YAP and TAZ. RAP2, YAP and TAZ have pivotal roles in mechanoregulated transcription, as deletion of YAP and TAZ abolishes the ECM stiffness-responsive transcriptome. Our findings show that RAP2 is a molecular switch in mechanotransduction, thereby defining a mechanosignalling pathway from ECM stiffness to the nucleus.

Permeability is one of the most important parameters to evaluate gas production in shale reservoirs. Because shale permeability is extremely low, gas is often used in the laboratory to measure permeability. However, the measured apparent gas permeability is higher than the intrinsic permeability due to the gas slippage effect, which could be even more dominant for materials with nanopores. Increasing gas pressure during tests reduces gas slippage effect, but it also decreases the effective stress which in turn influences the permeability. The coupled effect of gas slippage and effective stress on shale permeability remains unclear. Here we perform laboratory experiments on Longmaxi shale specimens to explore the coupled effect. We use the pressure transient method to measure permeability under different stress and pressure conditions. Our results reveal that the apparent measured permeability is controlled by these two competing effects. With increasing gas pressure, there exists a pressure threshold at which the dominant effect on permeability switches from gas slippage to effective stress. Based on the Klinkenberg model, we propose a new conceptual model that incorporates both competing effects. Combining microstructure analysis, we further discuss the roles of stress, gas pressure and water contents on gas permeability of shale.

Objective: To study the effects of cell immobilization on sulfide degradation ability and microbial community structure., Methods: Sulfide oxidizing microbiota was immobilized by entrapment on polyvinyl alcoholsodium alginate-activated carbon carrier. Sulfide degradation ability of the immobilized and free sulfide oxidizing microbiota was compared in sulfide-rich minimal medium. PCR-DGGE technique was used to reveal the effects of immobilization on microbial community structure., Results: The maximum sulfide degradation ability of the sulfide oxidizing microbiota in 12 h decreased from 1000 to 600 mg/L after immobilization. Community structure of the sulfide oxidizing microbiota changed after immobilization, but Catenococcus thiocycli was little affected. Thioclava pacifica was even strengthened in the microbiota after immobilization and sulfide degrading., Conclusion: In conclusion, limited by substrate diffusion and transfer in carrier material, sulfide degradation ability of the sulfide oxidizing microbiota under high sulfide concentration decreased after immobilization. Also, immobilization could affect the microbial community structure of sulfide oxidizing microbiota due to different adaptation ability to the microenvironment and adhesion ability to the carrier material.

Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. MicroRNAs (miRs) are a class of small, noncoding RNAs that have been implicated in the regulation of human diseases, including T2D. miR-26a is known to play a critical role in tumorigenesis; however, its function in cellular metabolism remains unknown. Here, we determined that miR-26a regulates insulin signaling and metabolism of glucose and lipids. Compared with lean individuals, overweight humans had decreased expression of miR-26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models compared with control animals. Global or liver-specific overexpression of miR-26a in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic glucose production, and decreased fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in conventional diet-fed mice impaired insulin sensitivity, enhanced glucose production, and increased fatty acid synthesis. miR-26a targeted several key regulators of hepatic metabolism and insulin signaling. These findings reveal miR-26a as a regulator of liver metabolism and suggest miR-26a should be further explored as a potential target for the treatment of T2D.