Unlocking the Potential of High Entropy Alloys in Electrochemical Water Splitting: A Review.

The global pursuit of sustainable energy is focused on producing hydrogen through electrocatalysis driven by renewable energy. Recently, High entropy alloys (HEAs) have taken the spotlight in electrolysis due to their intriguing cocktail effect, broad design space, customizable electronic structure, and entropy stabilization effect. The tunability and complexity of HEAs allow a diverse range of active sites, optimizing adsorption strength and activity for electrochemical water splitting. This review comprehensively covers contemporary advancements in synthesis technique, design framework, and physio-chemical evaluation approaches for HEA-based electrocatalysts. Additionally, it explores design principles and strategies aimed at optimizing the catalytic activity, stability, and effectiveness of HEAs in hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and overall water splitting. Through an in-depth investigation of these aspects, the complexity inherent in constituent element interactions, reaction processes, and active sites associated with HEAs is aimed to unravel. Eventually, an outlook regarding challenges and impending difficulties and an outline of the future direction of HEA in electrocatalysis is provided. The thorough knowledge offered in this review will assist in formulating and designing catalysts based on HEAs for the next generation of electrochemistry-related applications.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

Oxidation of selected fluoroquinolones by ferrate(VI) in water: Kinetics, mechanism, effects of constituents, and reaction pathways.

In this work, the oxidation of gatifloxacin (GAT), fleroxacin (FLE) and enoxacin (ENO) in aqueous solution by ferrate (Fe(VI)) was systemically investigated. Weak alkaline and high oxidant doses were favorable for the reaction. The pseudosecond-order rate constants were 0.18055, 0.29162, and 0.05476 L/(mg·min), and the activation energies were 25.13, 15.25, and 11.30 kJ/mol at pH = 8.00 and n(Fe(VI)):n(GAT) = 30:1, n(Fe(VI)):n(FLE) = 20:1, n(Fe(VI)):n(ENO) = 40:1 and a temperature of 25 °C. The maximum degradation rates of the GAT, FLE and ENO were 96.72%, 98.48% and 94.12%, respectively, well simulated by Response Surface Methodology. During the oxidation, the contribution of hydroxyl radicals (HO•) varied with time, whereas the final contribution was approximately 20% at 30 min. The removal efficiency was inhibited by anions by less than 10%, and cations by less than 25%, and significantly inhibited by high concentrations of humic acid. Moreover, two or three dominant reaction pathways were predicted, and the ring cleavages of quinolone and piperazine were mainly achieved through decarboxylation, demethlation and hydroxylation, and some pathways ended up with monocyclic chemicals, which were harmless to aquatic animals and plants. Theoretical calculations further proved that the reactions between FeO4- and neutral fluoroquinolone antibiotics were the major reactions. This work illustrates that Fe(VI) can efficiently remove fluoroquinolone antibiotics (FQs) in aqueous environments, and the results may contribute to the treatment of wastewater containing trace antibiotics and Fe(VI) chemistry.

The fertilization process in Lithocarpus dealbatus (Fagaceae) and its implication on the sexual reproduction evolution of Fagales.

MAIN CONCLUSION: The pistillate flowers of Lithocarpus dealbatus show two pollen tube (PT) arresting sites (the style-joining and micropyle) within the pistil during the postpollination-prezygotic stage. The PT, arrested at the pre-ovule stage, enhanced PT competition allowing the most compatible PTs to enter the ovary to ensure the highest fertilization success. During the shift from animal pollination to wind pollination, plants require a series of changes in reproductive traits. The mode of pollination is striking labile in Fagaceae. Lithocarpus is insect pollinated and is closely related to wind-pollinated Quercus. Little is known about the sexual reproduction of Lithocarpus. This study aimed to reveal the sexual reproduction of Lithocarpus dealbatus and to explore the evolutionary pattern of the key sexual reproduction traits to better understand their possible role in labile pollination. We found that after pollination, L. dealbatus PTs grew slowly in the style reaching style-joining in mid-January of the second year; then PT growth was arrested at style-joining for four months. Only two to three PTs resumed growth in mid-May to reach the micropyle, where PT growth ceased for one month before one PT resumed growth and passed through the micropyle to the embryo sac. Fagaceae showed a generalized mating system. Vast pollen production, small-sized pollen grains, long stigmatic receptive time, and reduced perianth were compatible with beetle pollination syndrome, representing the plesiomorphic status in Fagaceae. A large stigmatic surface and dry pollen grains linked to wind pollination might be independently derived several times in fagaceous lineages. Beetle pollination syndrome can cope with the uncertainty of pollinators to ensure conspecific pollen capture, which represents pre-adaptation status and has a selective advantage when conditions change, favouring wind pollination. The arrest of the PT at style-joining is a unique mechanism in later derived fagaceous lineages to enhance PT competition and promote outcrossing.

Seasonality and meteorological factors of HIV-negative cryptococcal meningitis in Guangdong Province, China.

OBJECTIVE: Information about the seasonal characteristics of human immunodeficiency virus (HIV)-negative cryptococcal meningitis (CM) is quite limited. The aim of this study was to explore the seasonality and meteorological factors of HIV-negative patients with CM. METHODS: We performed a retrospective study of 469 HIV-negative CM patients admitted to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. Their initial onset symptoms of CM occurred from January 2011 to December 2020. The temperature, precipitation, sunlight, humidity and wind speed for the corresponding period and the associated topographic, ecological type and soil type parameters data were collected. The Poisson regression model was used to determine the meteorological factors associated with CM onset. The geographical detector method was used to detect other environmental factors associated with CM onset. RESULTS: CM onset did not showed a seasonal fluctuation, but was strongly associated with mean temperature (ß = .010, p = .028) and mean relative humidity (ß = -.011, p = .006). In the rainy season, only mean wind speed remained significantly associated with CM onset (ß = -.108, p = .041). In the dry season, mean temperature (ß = .014, p = .016), mean relative humidity (ß = -.016, p = .006) and hours of sunlight (ß = -.002, p = .016) were significantly associated with CM onset. Topographic, ecological type and soil type factors did not add explanatory power. CONCLUSIONS: Our findings add the knowledge about the environmental factors of HIV-negative CM. Meteorological factors, especially temperature and humidity, may be the main environmental factors affecting the onset of HIV-negative CM.

Comparison and Characterization of Phenotypic and Genomic Mutations Induced by a Carbon-Ion Beam and Gamma-ray Irradiation in Soybean (Glycine max (L.) Merr.).

Soybean (Glycine max (L.) Merr.) is a nutritious crop that can provide both oil and protein. A variety of mutagenesis methods have been proposed to obtain better soybean germplasm resources. Among the different types of physical mutagens, carbon-ion beams are considered to be highly efficient with high linear energy transfer (LET), and gamma rays have also been widely used for mutation breeding. However, systematic knowledge of the mutagenic effects of these two mutagens during development and on phenotypic and genomic mutations has not yet been elucidated in soybean. To this end, dry seeds of Williams 82 soybean were irradiated with a carbon-ion beam and gamma rays. The biological effects of the M1 generation included changes in survival rate, yield and fertility. Compared with gamma rays, the relative biological effectiveness (RBE) of the carbon-ion beams was between 2.5 and 3.0. Furthermore, the optimal dose for soybean was determined to be 101 Gy to 115 Gy when using the carbon-ion beam, and it was 263 Gy to 343 Gy when using gamma rays. A total of 325 screened mutant families were detected from out of 2000 M2 families using the carbon-ion beam, and 336 screened mutant families were found using gamma rays. Regarding the screened phenotypic M2 mutations, the proportion of low-frequency phenotypic mutations was 23.4% when using a carbon ion beam, and the proportion was 9.8% when using gamma rays. Low-frequency phenotypic mutations were easily obtained with the carbon-ion beam. After screening the mutations from the M2 generation, their stability was verified, and the genome mutation spectrum of M3 was systemically profiled. A variety of mutations, including single-base substitutions (SBSs), insertion-deletion mutations (INDELs), multinucleotide variants (MNVs) and structural variants (SVs) were detected with both carbon-ion beam irradiation and gamma-ray irradiation. Overall, 1988 homozygous mutations and 9695 homozygous + heterozygous genotype mutations were detected when using the carbon-ion beam. Additionally, 5279 homozygous mutations and 14,243 homozygous + heterozygous genotype mutations were detected when using gamma rays. The carbon-ion beam, which resulted in low levels of background mutations, has the potential to alleviate the problems caused by linkage drag in soybean mutation breeding. Regarding the genomic mutations, when using the carbon-ion beam, the proportion of homozygous-genotype SVs was 0.45%, and that of homozygous + heterozygous-genotype SVs was 6.27%; meanwhile, the proportions were 0.04% and 4.04% when using gamma rays. A higher proportion of SVs were detected when using the carbon ion beam. The gene effects of missense mutations were greater under carbon-ion beam irradiation, and the gene effects of nonsense mutations were greater under gamma-ray irradiation, which meant that the changes in the amino acid sequences were different between the carbon-ion beam and gamma rays. Taken together, our results demonstrate that both carbon-ion beam and gamma rays are effective techniques for rapid mutation breeding in soybean. If one would like to obtain mutations with a low-frequency phenotype, low levels of background genomic mutations and mutations with a higher proportion of SVs, carbon-ion beams are the best choice.

Physiological and Transcriptomic Analyses Reveal the Effects of Carbon-Ion Beam on Taraxacum kok-saghyz Rodin Adventitious Buds.

Taraxacum kok-saghyz Rodin (TKS) has great potential as an alternative natural-rubber (NR)-producing crop. The germplasm innovation of TKS still faces great challenges due to its self-incompatibility. Carbon-ion beam (CIB) irradiation is a powerful and non-species-specific physical method for mutation creation. Thus far, the CIB has not been utilized in TKS. To better inform future mutation breeding for TKS by the CIB and provide a basis for dose-selection, adventitious buds, which not only can avoid high levels of heterozygosity, but also further improve breeding efficiency, were irradiated here, and the dynamic changes of the growth and physiologic parameters, as well as gene expression pattern were profiled, comprehensively. The results showed that the CIB (5-40 Gy) caused significant biological effects on TKS, exhibiting inhibitory effects on the fresh weight and the number of regenerated buds and roots. Then,15 Gy was chosen for further study after comprehensive consideration. CIB-15 Gy resulted in significant oxidative damages (hydroxyl radical (OH•) generation activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and malondialdehyde (MDA) content) and activated the antioxidant system (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX)) of TKS. Based on RNA-seq analysis, the number of differentially expressed genes (DEGs) peaked at 2 h after CIB irradiation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DNA-replication-/repair- (mainly up-regulated), cell-death- (mainly up-regulated), plant-hormone- (auxin and cytokinin, which are related to plant morphogenesis, were mainly down-regulated), and photosynthesis- (mainly down-regulated) related pathways were involved in the response to the CIB. Furthermore, CIB irradiation can also up-regulate the genes involved in NR metabolism, which provides an alternative strategy to elevate the NR production in TKS in the future. These findings are helpful to understand the radiation response mechanism and further guide the future mutation breeding for TKS by the CIB.

Variation of NK, NKT, CD4+ T, CD8+ T cells, and IL-17A by CalliSpheres® microspheres-transarterial chemoembolization in refractory liver metastases patients.

Immune environment plays an important role in the management of liver cancer. The current study aimed to explore the change of NK and NKT cells, IL-17A, CD4+ T and CD8+ T cells in refractory liver metastases patients before and after CalliSpheres® microspheres transarterial chemoembolization (CSM-TACE). Peripheral blood (PB) samples from 35 refractory liver metastases patients were collected before CSM-TACE (baseline), 2 days (D2) and 5 days (D5) after CSM-TACE. Then, NK and NKT cells, IL-17A, CD4+ T and CD8+ T cells from PB samples were detected. All enrolled patients successfully completed CSM-TACE procedure and achieved disease control rate of 100% after 1 month. NKT cells were increased from baseline to D2 and D5 [median (range): 5.88% (1.53%-12.05%) vs. 9.54% (5.19%-15.71%) vs. 7.12% (2.77%-13.29%)], NK cells were also enhanced from baseline to D2 and D5 [median (range): 14.35% (5.85%-20.52%) vs. 20.36% (15.88%-27.30%) vs. 30.82% (22.18%-37.72%)], while IL-17A was declined from baseline to D2 and D5 [median (range): 22.11 (9.46-39.18) pg/ml vs. 12.41 (3.24-26.84) pg/ml vs. 6.55 (1.11-20.98) pg/ml]. Furthermore, IL-17A was negatively correlated with the NK and NKT cells at baseline, D2 and D5 (all p < .05), respectively. Additionally, CD4+ T cells and CD4+ T/CD8+ T ratio were increased while CD8+ T cells were declined from baseline to D2 and D5 (all p < .05). NK cells, NKT cells, and CD4+ T cells are increased but IL-17A and CD8+ T cells are declined after CSM-TACE in refractory liver metastases.

Frequency and Spectrum of Mutations Induced by Gamma Rays Revealed by Phenotype Screening and Whole-Genome Re-Sequencing in Arabidopsis thaliana.

Genetic variations are an important source of germplasm diversity, as it provides an allele resource that contributes to the development of new traits for plant breeding. Gamma rays have been widely used as a physical agent for mutation creation in plants, and their mutagenic effect has attracted extensive attention. However, few studies are available on the comprehensive mutation profile at both the large-scale phenotype mutation screening and whole-genome mutation scanning. In this study, biological effects on M1 generation, large-scale phenotype screening in M2 generation, as well as whole-genome re-sequencing of seven M3 phenotype-visible lines were carried out to comprehensively evaluate the mutagenic effects of gamma rays on Arabidopsis thaliana. A total of 417 plants with visible mutated phenotypes were isolated from 20,502 M2 plants, and the phenotypic mutation frequency of gamma rays was 2.03% in Arabidopsis thaliana. On average, there were 21.57 single-base substitutions (SBSs) and 11.57 small insertions and deletions (InDels) in each line. Single-base InDels accounts for 66.7% of the small InDels. The genomic mutation frequency was 2.78 × 10-10/bp/Gy. The ratio of transition/transversion was 1.60, and 64.28% of the C > T events exhibited the pyrimidine dinucleotide sequence; 69.14% of the small InDels were located in the sequence with 1 to 4 bp terminal microhomology that was used for DNA end rejoining, while SBSs were less dependent on terminal microhomology. Nine genes, on average, were predicted to suffer from functional alteration in each re-sequenced line. This indicated that a suitable mutation gene density was an advantage of gamma rays when trying to improve elite materials for one certain or a few traits. These results will aid the full understanding of the mutagenic effects and mechanisms of gamma rays and provide a basis for suitable mutagen selection and parameter design, which can further facilitate the development of more controlled mutagenesis methods for plant mutation breeding.

Genome and transcriptome-based characterization of high energy carbon-ion beam irradiation induced delayed flower senescence mutant in Lotus japonicus.

BACKGROUND: Flower longevity is closely related to pollen dispersal and reproductive success in all plants, as well as the commercial value of ornamental plants. Mutants that display variation in flower longevity are useful tools for understanding the mechanisms underlying this trait. Heavy-ion beam irradiation has great potential to improve flower shapes and colors; however, few studies are available on the mutation of flower senescence in leguminous plants. RESULTS: A mutant (C416) exhibiting blossom duration eight times longer than that of the wild type (WT) was isolated in Lotus japonicus derived from carbon ion beam irradiation. Genetic assays supported that the delayed flower senescence of C416 was a dominant trait controlled by a single gene, which was located between 4,616,611 Mb and 5,331,876 Mb on chromosome III. By using a sorting strategy of multi-sample parallel genome sequencing, candidate genes were narrowed to the gene CUFF.40834, which exhibited high identity to ethylene receptor 1 in other model plants. A physiological assay demonstrated that C416 was insensitive to ethylene precursor. Furthermore, the dynamic changes of phytohormone regulatory network in petals at different developmental stages was compared by using RNA-seq. In brief, the ethylene, jasmonic acid (JA), and salicylic acid (SA) signaling pathways were negatively regulated in C416, whereas the brassinosteroid (BR) and cytokinin signaling pathways were positively regulated, and auxin exhibited dual effects on flower senescence in Lotus japonicus. The abscisic acid (ABA) signaling pathway is positively regulated in C416. CONCLUSION: So far, C416 might be the first reported mutant carrying a mutation in an endogenous ethylene-related gene in Lotus japonicus, rather than through the introduction of exogenous genes by transgenic techniques. A schematic of the flower senescence of Lotus japonicus from the perspective of the phytohormone regulatory network was provided based on transcriptome profiling of petals at different developmental stages. This study is informative for elucidating the molecular mechanism of delayed flower senescence in C416, and lays a foundation for candidate flower senescence gene identification in Lotus japonicus. It also provides another perspective for the improvement of flower longevity in legume plants by heavy-ion beam.

Discovery of a novel short peptide with efficacy in accelerating the healing of skin wounds.

Despite extensive efforts to develop efficacious therapeutic approaches, the treatment of skin wounds remains a considerable clinical challenge. Existing remedies cannot sufficiently meet current needs, so the discovery of novel pro-healing agents is of growing importance. In the current research, we identified a novel short peptide (named RL-QN15, primary sequence 'QNSYADLWCQFHYMC') from Rana limnocharis skin secretions, which accelerated wound healing in mice. Exploration of the underlying mechanisms showed that RL-QN15 activated the MAPK and Smad signaling pathways, and selectively modulated the secretion of cytokines from macrophages. This resulted in the proliferation and migration of skin cells and dynamic regulation of TGF-ß1 and TGF-ß3 in wounds, which accelerated re-epithelialization and granulation tissue formation and thus skin regeneration. Moreover, RL-QN15 showed significant therapeutic potency against chronic wounds, skin fibrosis, and oral ulcers. Our results highlight frog skin secretions as a potential treasure trove of bioactive peptides with healing activity. The novel peptide (RL-QN15) identified in this research shows considerable capacity as a candidate for the development of novel pro-healing agents.

Regulated aberrant amygdala functional connectivity in premenstrual syndrome via electro-acupuncture stimulation at sanyinjiao acupoint（SP6）.

Background: Acupuncture is an effective therapy for premenstrual syndrome (PMS). However, the mechanisms behind this method are still unclear. Our previous study found that aberrant amygdala resting-state functional networks were involved in PMS. Thereby, a deep investigation on the alterations of amygdala resting-state functional networks induced by acupuncture stimulation might contribute to a better understanding of the intricate mechanisms of acupuncture treatment on PMS. Methods: Twenty three PMS patients were recruited in this study. All patients received a 6-minute electro-acupuncture stimulation (EAS) at Sanyinjiao acupoint (SP6) and underwent two 6-minute resting-state fMRI scannings before and after EAS. With amygdala as the seed region, functional connectivity (FC) method was adopted to examine EAS-related modulation of intrinsic connectivity in PMS patients by comparing pre-EAS. Results: The results showed that EAS at SP6 induced increased FC between the left amygdala and brainstem, right hippocampus, and decreased FC between the left amygdala and left thalamus, bilateral supplementary motor area (SMA). Moreover, the results also showed that EAS at SP6 induced increased FC between the right amygdala and brainstem, right hippocampus, right orbitofrontal cortex, bilateral anterior cingulate cortex (ACC), and decreased FC between the right amygdala and right SMA. Conclusions: Based on the results of our previous study, our findings might improve our understanding of neural mechanisms behind acupuncture effects on PMS.

Altered fractional amplitude of low-frequency fluctuation in women with premenstrual syndrome via acupuncture at Sanyinjiao (SP6).

BACKGROUND: Premenstrual syndrome (PMS) is a prevalent gynecological disease and is significantly associated with abnormal neural activity. Acupuncture is an effective treatment on PMS in clinical practice. However, few studies have been performed to investigate whether acupuncture might modulate the abnormal neural activity in patients with PMS. Thereby, the aim of the study was to assess alterations of the brain activity induced by acupuncture stimulation in PMS patients. METHODS: Twenty PMS patients were enrolled in this study. All patients received a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) scan before and after electro-acupuncturing stimulation (EAS) at Sanyinjiao (SP6) acupoint in the late luteal phase of menstrual. Fractional amplitude of low-frequency fluctuation (fALFF) method was applied to examine the EAS-related brain changes in PMS patients. RESULTS: Compared with pre-EAS at SP6, increased fALFF value in several brain regions induced by SP6, including brainstem, right thalamus, bilateral insula, right paracentral lobule, bilateral cerebellum, meanwhile, decreased fALFF in the left cuneus, right precuneus, left inferior temporal cortex. CONCLUSIONS: Our findings provide imaging evidence to support that SP6-related acupuncture stimulation may modulate the neural activity in patients with PMS. This study may partly interpret the neural mechanisms of acupuncture at SP6 which is used to treat PMS patients in clinical. TRIAL REGISTRATION: The study was registered on http://www.chictr.org.cn . The Clinical Trial Registration Number is ChiCTR-OPC-15005918, registry in 29/01/2015.

Kaempferol-induced GPER upregulation attenuates atherosclerosis via the PI3K/AKT/Nrf2 pathway.

CONTEXT: The effect of kaempferol, a regulator of oestrogen receptors, on atherosclerosis (AS) and the underlying mechanism is elusive. OBJECTIVE: To explore the effect and mechanism of kaempferol on AS. METHODS AND MATERIALS: In vivo, C57BL/6 and apolipoprotein E (APOE)-/- mice were randomly categorized into six groups (C57BL/6: control, ovariectomy (OVX), high-fat diet (HFD); APOE-/-: OVX-HFD, OVX-HFD + kaempferol (50 mg/kg) and OVX-HFD + kaempferol (100 mg/kg) and administered with kaempferol for 16 weeks, intragastrically. Oil-Red and haematoxylin-eosin (HE) staining were employed to examine the effect of kaempferol. In vitro, human aortic endothelial cells (HAECs) were pre-treated with or without kaempferol (5, 10 or 20 µM), followed by administration with kaempferol and oxidized low-density lipoprotein (ox-LDL) (200 µg/mL). The effect of kaempferol was evaluated using flow cytometry, and TdT-mediated dUTP Nick-End Labelling (TUNEL). RESULTS: In vivo, kaempferol (50 and 100 mg/kg) normalized the morphology of blood vessels and lipid levels and suppressed inflammation and apoptosis. It also activated the G protein-coupled oestrogen receptor (GPER) and PI3K/AKT/nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. In vitro, ox-LDL (200 µg/mL) reduced the cell viability to 50% (IC50). Kaempferol (5, 10 or 20 µM) induced-GPER activation increased cell viability to nearly 10%, 19.8%, 30%, and the decreased cellular reactive oxygen species (ROS) generation (16.7%, 25.6%, 31.1%), respectively, consequently attenuating postmenopausal AS. However, the protective effects of kaempferol were blocked through co-treatment with si-GPER. CONCLUSIONS: The beneficial effects of kaempferol against postmenopausal AS are associated with the PI3K/AKT/Nrf2 pathways, mediated by the activation of GPER.

Mutation spectrum and genotype-phenotype correlation of inherited retinal dystrophy in Taiwan.

BACKGROUND: Inherited retinal dystrophy (IRD) is a group of irreversible retinal degenerative disorders with significant genotypic and phenotypic heterogeneity, which cause difficulty in making a precise clinical diagnosis. Furthermore, the mutation spectrum of IRD in Taiwan remains unknown. Therefore, our study focused on investigating the spectrum of mutations among Taiwanese families with IRD using targeted exome sequencing (TES) technology. METHODS: We recruited a total of 60 unrelated Taiwanese families with IRD; most of them were retinitis pigmentosa. We employed TES to investigate 284 candidate genes. Bioinformatics analysis, Sanger sequencing-based co-segregation testing, and computational assessment were performed to validate each mutation and its pathogenicity. The genotype-phenotype correlation was analysed in all patients with mutations defined in the guidelines provided by the American College of Medical Genetics. RESULTS: We successfully identified genetic causes in 32 families (detection rate of 53.3%). Among them, 16 had a sporadic inheritance (16/36, 44.4%); eight had an autosomal recessive inheritance (8/14, 57.1%); four had an autosomal dominant inheritance (4/5, 80%); four had an X-linked inheritance (4/5, 80%). Among 38 pathological mutations in 19 known genes, 20 mutations are reported here for the first time. Novel mutation spectrum and genotype-phenotype correlations were revealed as well. CONCLUSION: Here we achieved a detection rate of 53.3% and elucidated the mutation spectrum in Taiwanese families with IRD for the first time. The results indicated that CYP4V2 and USH2A might be the most common pathogenic genes in IRD patients in Taiwan.

Targeting valosin-containing protein enhances the efficacy of radiation therapy in esophageal squamous cell carcinoma.

Overcoming resistance to radiation is a great challenge in cancer therapy. Here, we highlight that targeting valosin-containing protein (VCP) improves radiation sensitivity in esophageal squamous cell carcinoma (ESCC) cell lines and show the potential of using VCP as a prognosis marker in locally advanced ESCC treated with radiation therapy. Esophageal squamous cell carcinoma cell lines with high VCP expression were treated with VCP inhibitor combined with radiotherapy. Cell proliferation, colony formation, cell death, and endoplasmic reticulum (ER) stress signaling were evaluated. Moreover, patients with newly diagnosed locally advanced ESCC who were treated with radiotherapy were analyzed. Immunohistochemistry was used to detect the expression of VCP. The correlation between overall survival and VCP was investigated. Esophageal squamous cell carcinoma cells treated with VCP inhibitor and radiotherapy showed attenuated cell proliferation and colony formation and enhanced apoptosis. Further investigation showed this combined strategy activated the ER stress signaling involved in unfolded protein response, and inhibited the ER-associated degradation (ERAD) pathway. Clinical analysis revealed a significant survival benefit in the low VCP expression group. Targeting VCP resulted in antitumor activity and enhanced the efficacy of radiation therapy in ESCC cells in vitro. Valosin-containing protein is a promising and novel target. In patients with locally advanced ESCC who received radiotherapy, VCP can be considered as a useful prognostic indicator of overall survival. Valosin-containing protein inhibitors could be developed for use as effective cancer therapies, in combination with radiation therapy.

Low tumour PPM1H indicates poor prognosis in colorectal cancer via activation of cancer-associated fibroblasts.

BACKGROUND: Vimentin (VIM) is considered a prognostic marker in colorectal cancer (CRC). Our aim is to identify genes that fulfil a "X-low implies VIM-high" Boolean relationship and to evaluate their prognostic value and potential mechanism. METHODS: Potential biomarkers related to VIM expression were searched using a bioinformatics approach across gene-expression arrays. Based on subgroup analysis of 2 CRC cohorts, the selected gene was tested for its association with patient's survival outcomes. The regulatory link between the selected gene and VIM was further examined with in vitro models. RESULTS: PPM1H was identified as the top candidate in our search. Patients with PPM1H-low tumours have a lower 5-year disease-free survival rate than patients with PPM1H-high tumours in 2 independent cohorts. In multivariate Cox analysis, patients with PPM1H-low tumours were independently associated with relapse in both the discovery cohort (hazard ratio [HR], 1.362; 95% confidence interval [CI], 1.015-1.826; P = 0.039) and the validation cohort (HR for DFS, 4.052; 95% CI, 2.634-6.234; P < 0.001). PPM1H knockdown in CRC cells and growth in the corresponding conditional medium increased VIM expression and colon fibroblast proliferation, indicating a transformation of cancer-association fibroblasts (CAFs). Conversely, educated CAFs also facilitated the growth of CRC cells with low PPM1H expression. CONCLUSIONS: Lack of tumour PPM1H expression identifies a patient subgroup with a high relapse risk, and CRC cells with low expression of PPM1H activate CAFs and inversely get promoted by CAFs.

Leaf anatomy of a late Palaeozoic cycad.

Today, cycads are a small group of gymnospermous plants with a limited distribution in the (sub)tropics, but they were major constituents of Mesozoic floras. Fossil leaves sporadically found in latest Carboniferous and Permian floras have putatively been ascribed to cycads. However, their true affinity remains unclear due to the lack of anatomical evidence. Virtually all modern cycads have pinnate leaves, but this type of leaf morphology is by no means unique for cycads. Pinnate leaves of Plagiozamites oblongifolius Halle 1927 with well-preserved cuticles showing the epidermal anatomy are here described from the upper Permian Xuanwei Formation of Yunnan Province, Southwest China. The cuticles show a clear differentiation into costal and intercostal zones; stomata are confined to the intercostal zones on both the upper and lower leaf surfaces. The external morphology and the epidermal anatomy of these fossil leaves are closely comparable with those of extant cycads, particularly members of the family Zamiaceae.

Serum Thyroglobulin-A Sensitive Biomarker of Iodine Nutrition Status and Affected by Thyroid Abnormalities and Disease in Adult Populations.

OBJECTIVE: To evaluate the usefulness of the thyroglobulin (Tg) level in adults as a nutritional biomarker of iodine status and to identify the factors related to the serum Tg level. METHODS: A cross-sectional study was conducted in adult populations of areas differing in iodine nutrition from three provinces (Autonomous Region) in China. Serum levels of thyroid hormones and Tg as well as thyroid autoantibodies were measured. The thyroid volume and nodule were measured by ultrasound. A multivariate linear regression analysis was used to assess iodine intake and other indeterminate factors associated with the serum Tg level. RESULTS: A total of 573 adults were recruited for this study. The serum Tg levels differed significantly among the three groups (22.27 µg/L, 9.73 µg/L and 15.77 µg/L in the excess, more-than-adequate, and deficient groups, respectively). The results of multivariate linear regression analysis indicate that excess and deficient iodine intake, goiter, thyroid nodule, hypothyroidism are significantly related with higher Tg level, and TgAb positivity is significantly related with lower serum Tg. CONCLUSION: The serum Tg level reflects abnormal thyroid function and is a sensitive functional biomarker of iodine nutrition status.

Unconventional Superconductivity in the Layered Iron Germanide YFe(2)Ge(2).

The iron-based intermetallic YFe_{2}Ge_{2} stands out among transition metal compounds for its high Sommerfeld coefficient of the order of 100 mJ/(mol K^{2}), which signals strong electronic correlations. A new generation of high quality samples of YFe_{2}Ge_{2} show superconducting transition anomalies below 1.8 K in thermodynamic, magnetic, and transport measurements, establishing that superconductivity is intrinsic in this layered iron compound outside the known superconducting iron pnictide or chalcogenide families. The Fermi surface geometry of YFe_{2}Ge_{2} resembles that of KFe_{2}As_{2} in the high pressure collapsed tetragonal phase, in which superconductivity at temperatures as high as 10 K has recently been reported, suggesting an underlying connection between the two systems.