Long-chain polyunsaturated fatty acid metabolism in carnivorous marine teleosts: insight into the profile of endogenous biosynthesis in golden pompano Trachinotus ovatus

Golden pompano Trachinotus ovatus is an important farmed carnivorous marine teleost. Although some enzymes for long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis have been identified, the ability of T. ovatus for endogenous biosynthesis is unknown. Here, we evaluated in vivo LC-PUFA synthesis in a 56-day culture experiment using six diets (D1-D6) formulated with linseed and soybean oils to produce dietary linolenic/linoleic acid (ALA/LA) ratios ranging from 0.14 to 2.20. The control diet (D0) used fish oil as lipid source. The results showed that, compared with the corresponding indeces of fish fed D0, the weight gain rate and specific growth rate, as well as the contents of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in tissues (liver, muscle, brain and eye) of D1-D6 groups were significantly lower (P < 0.05). These data suggested that T. ovatus could not synthesize LC-PUFA from C18 PUFA or such ability was very low. However, tissue levels of 20:4n-3 in fish fed diets D1-D6 were higher than that of D0 fish (P < 0.05), and positively correlated with dietary ALA/LA ratio, while levels of EPA showed no difference among the D1-D6 groups. These results indicated that Δ5 desaturation, required for the conversion of 20:4n-3 to EPA, may be lacking or very low, suggesting incomplete LC-PUFA biosynthesis ability in T. ovatus

Characterization of the Genomic Landscape in Cervical Cancer by Next Generation Sequencing

Cervical cancer is the fourth leading cause of cancer-related deaths in women worldwide. Although many sequencing studies have been carried out, the genetic characteristics of cervical cancer remain to be fully elucidated, especially in the Asian population. Herein, we investigated the genetic landscape of Chinese cervical cancer patients using a validated multigene next generation sequencing (NGS) panel. We analyzed 64 samples, consisting of 32 tumors and 32 blood samples from 32 Chinese cervical cancer patients by performing multigene NGS with a panel targeting 571 cancer-related genes. A total of 810 somatic variants, 2730 germline mutations and 701 copy number variations (CNVs) were identified. FAT1, HLA-B, PIK3CA, MTOR, KMT2D and ZFHX3 were the most mutated genes. Further, PIK3CA, BRCA1, BRCA2, ATM and TP53 gene loci had a higher frequency of CNVs. Moreover, the role of PIK3CA in cervical cancer was further highlighted by comparing with the ONCOKB database, especially for E545K and E542K, which were reported to confer radioresistance to cervical cancer. Notably, analysis of potential therapeutic targets suggested that cervical cancer patients could benefit from PARP inhibitors. This multigene NGS analysis revealed several novel genetic alterations in Chinese patients with cervical cancer and highlighted the role of PIK3CA in cervical cancer. Overall, this study showed that genetic variations not only affect the genetic susceptibility of cervical cancer, but also influence the resistance of cervical cancer to radiotherapy, but further studies involving a larger patient population should be undertaken to validate these findings

A study of temperature variability on admissions and deaths for cardiovascular diseases in Northwestern China

Abstract Objective To explore the effect of temperature variability (TV) on admissions and deaths for cardiovascular diseases (CVDs). Method The admissions data of CVDs were collected in 4 general hospitals in Jinchang City, Gansu Province from 2013 to 2016. The monitoring data of death for CVDs from 2013 to 2017 were collected through the Jinchang City Center for Disease Control and Prevention. Distributed lag nonlinear model (DLNM) was combined to analyze the effects of TV (daily temperature variability (DTV) and hourly temperature variability (HTV)) on the admissions and deaths for CVDs after adjusting confounding effects. Stratified analysis was conducted by age and gender. Then the attribution risk of TV was evaluated. Results There was a broadly linear correlation between TV and the admissions and deaths for CVDs, but only the association between TV and outpatient and emergency room (O&ER) visits for CVDs have statistically significant. DTV and HTV have similar lag effect. Every 1 ℃ increase in DTV and HTV was associated with a 3.61% (95% CI: 1.19% ~ 6.08%), 3.03% (95% CI: 0.27% ~ 5.86%) increase in O&ER visits for CVDs, respectively. There were 22.75% and 14.15% O&ER visits for CVDs can attribute to DTV and HTV exposure during 2013–2016. Males and the elderly may be more sensitive to the changes of TV. Greater effect of TV was observed in non-heating season than in heating season. Conclusion TV was an independent risk factor for the increase of O&ER visits for CVDs, suggesting effective guidance such as strengthening the timely prevention for vulnerable groups before or after exposure, which has important implications for risk management of CVDs

Predictive value of total cholesterol to high‐density lipoprotein cholesterol ratio for chronic kidney disease among adult male and female in Northwest China

Abstract Background Studies have found that the ratio of total cholesterol to high‐density lipoprotein cholesterol (TC/HDL‐C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females. Methods Based on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL‐C, TC/HDL‐C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve. Results During a mean follow‐up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL‐C and TC/HDL‐C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05–1.31), 0.84 (0.71–0.99), and 1.15 (1.06–1.25) for males, 0.94 (0.78–1.13), 0.58 (0.35–0.95), and 1.19 (1.01–1.40) for females, respectively. The results also showed that TC, HDL‐C, and TC/HDL‐C were associated with CKD in a linear dose–response relationship. The TC/HDL‐C had the largest area under the curve (AUC) compared to TC and HDL‐C, and the AUC among the females was larger than that among males. Conclusions The TC/HDL‐C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL‐C, especially in females

A novel role of proteasomal beta 1 subunit in tumorigenesis

National Science Foundation of China [81071670]; Department of Science and Technology, Fujian Province, China [2009I0026]; Xiamen Center for Brain Research, China [NK5888]p27(Kip1) is a key cell-cycle regulator whose level is primarily regulated by the ubiquitin- proteasome degradation pathway. Its beta 1 subunit is one of seven beta subunits that form the beta-ring of the 20S proteasome, which is responsible for degradation of ubiquitinated proteins. We report here that the beta 1 subunit is up-regulated in oesophageal cancer tissues and some ovarian cancer cell lines. It promotes cell growth and migration, as well as colony formation. beta 1 binds and degrades p27(Kip1)directly. Interestingly, the lack of phosphorylation at Ser(158) of the beta 1 subunit promotes degradation of p27(Kip1). We therefore propose that the beta 1 subunit plays a novel role in tumorigenesis by degrading p27(Kip1)

Ambipolar Phosphine Derivatives to Attain True Blue OLEDs with 6.5% EQE

A family of new branched phosphine derivatives {Ph₂N–(C₆H₄)_<i>n</i>−}₃P → E (E = O <b>1</b>–<b>3</b>, <i>n</i> = 1–3; E = S <b>4</b>–<b>6</b>, <i>n</i> = 1–3; E = Se <b>7</b>–<b>9</b>, <i>n</i> = 1–3; E = AuC₆F₅ <b>4</b>–<b>6</b>, <i>n</i> = 1–3), which are the donor–acceptor type molecules, exhibit efficient deep blue room temperature fluorescence (λ_em = 403–483 nm in CH₂Cl₂ solution, λ_em = 400–469 nm in the solid state). Fine tuning the emission characteristics can be achieved varying the length of aromatic oligophenylene bridge −(C₆H₄)_<i>n</i>–. The pyramidal geometry of central R₃P → E fragment on the one hand disrupts π-conjugation between the branches to preserve blue luminescence and high triplet energy, while on the other hand provides amorphous materials to prevent excimer formation and fluorescence self-quenching. Hence, compounds <b>2</b>, <b>3</b>, <b>5</b>, and <b>12</b> were used as emitters to fabricate nondoped and doped electroluminescent devices. The luminophore <b>2</b> (E = O, <i>n</i> = 2) demonstrates excellently balanced bipolar charge transport and good nondoped device performance with a maximum external quantum efficiency (EQE_max) of 3.3% at 250 cd/m² and Commission International de L’Eclairage (CIE) coordinates of (0.15, 0.08). The doped device of <b>3</b> (E = O, <i>n</i> = 3) shows higher efficiency (EQE_max of 6.5, 6.0 at 100 cd/m²) and high color purity with CIE (0.15, 0.06) that matches the HDTV standard blue. The time-resolved electroluminescence measurement indicates that high efficiency of the device can be attributed to the triplet–triplet annihilation to enhance generation of singlet excitons

Ambipolar Phosphine Derivatives to Attain True Blue OLEDs with 6.5% EQE

A family of new branched phosphine derivatives {Ph₂N–(C₆H₄)_<i>n</i>−}₃P → E (E = O <b>1</b>–<b>3</b>, <i>n</i> = 1–3; E = S <b>4</b>–<b>6</b>, <i>n</i> = 1–3; E = Se <b>7</b>–<b>9</b>, <i>n</i> = 1–3; E = AuC₆F₅ <b>4</b>–<b>6</b>, <i>n</i> = 1–3), which are the donor–acceptor type molecules, exhibit efficient deep blue room temperature fluorescence (λ_em = 403–483 nm in CH₂Cl₂ solution, λ_em = 400–469 nm in the solid state). Fine tuning the emission characteristics can be achieved varying the length of aromatic oligophenylene bridge −(C₆H₄)_<i>n</i>–. The pyramidal geometry of central R₃P → E fragment on the one hand disrupts π-conjugation between the branches to preserve blue luminescence and high triplet energy, while on the other hand provides amorphous materials to prevent excimer formation and fluorescence self-quenching. Hence, compounds <b>2</b>, <b>3</b>, <b>5</b>, and <b>12</b> were used as emitters to fabricate nondoped and doped electroluminescent devices. The luminophore <b>2</b> (E = O, <i>n</i> = 2) demonstrates excellently balanced bipolar charge transport and good nondoped device performance with a maximum external quantum efficiency (EQE_max) of 3.3% at 250 cd/m² and Commission International de L’Eclairage (CIE) coordinates of (0.15, 0.08). The doped device of <b>3</b> (E = O, <i>n</i> = 3) shows higher efficiency (EQE_max of 6.5, 6.0 at 100 cd/m²) and high color purity with CIE (0.15, 0.06) that matches the HDTV standard blue. The time-resolved electroluminescence measurement indicates that high efficiency of the device can be attributed to the triplet–triplet annihilation to enhance generation of singlet excitons

Single‐cell landscape of the cellular microenvironment in three different colonic polyp subtypes in children

Abstract Background The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz–Jeghers syndrome (PJS) remains limited. Methods We conducted single‐cell RNA sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients. Results We identified both shared and disease‐specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial–mesenchymal transition (EMT)‐like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon‐related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber‐associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption‐related genes. In addition, the TNF‐α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell–cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps. Conclusion These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children

A Monomeric Membrane Peptide that Lives in Three Worlds: In Solution, Attached to, and Inserted across Lipid Bilayers

The membrane peptide pH (low) insertion peptide (pHLIP) lives in three worlds, being soluble in aqueous solution at pH 7.4, binding to the surface of lipid bilayers, and inserting as a transbilayer helix at low pH. With low pH driving the process, pHLIP can translocate cargo molecules attached to its C-terminus via a disulfide and release them in the cytoplasm of a cell. Here we examine a key aspect of the mechanism, showing that pHLIP is monomeric in each of its three major states: soluble in water near neutral pH (state I), bound to the surface of a membrane near neutral pH (state II), and inserted across the membrane as an α-helix at low pH (state III). The peptide does not induce fusion or membrane leakage. The unique properties of pHLIP made it attractive for the biophysical investigation of membrane protein folding in vitro and for the development of a novel class of delivery peptides for the transport of therapeutic and diagnostic agents to acidic tissue sites associated with various pathological processes in vivo