FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis.

Radiotherapy is one of the standard therapeutic regimens for medulloblastoma (MB). Tumor cells utilize DNA damage repair (DDR) mechanisms to survive and develop resistance during radiotherapy. It has been found that targeting DDR sensitizes tumor cells to radiotherapy in several types of cancer, but whether and how DDR pathways are involved in the MB radiotherapy response remain to be determined. Single-cell RNA sequencing was carried out on 38 MB tissues, followed by expression enrichment assays. Fanconi anemia group D2 gene (FANCD2) expression was evaluated in MB samples and public MB databases. The function of FANCD2 in MB cells was examined using cell counting assays (CCK-8), clone formation, lactate dehydrogenase activity, and in mouse orthotopic models. The FANCD2-related signaling pathway was investigated using assays of peroxidation, a malondialdehyde assay, a reduced glutathione assay, and using FerroOrange to assess intracellular iron ions (Fe2+ ). Here, we report that FANCD2 was highly expressed in the malignant sonic hedgehog (SHH) MB subtype (SHH-MB). FANCD2 played an oncogenic role and predicted worse prognosis in SHH-MB patients. Moreover, FANCD2 knockdown markedly suppressed viability, mobility, and growth of SHH-MB cells and sensitized SHH-MB cells to irradiation. Mechanistically, FANCD2 deficiency led to an accumulation of Fe2+ due to increased divalent metal transporter 1 expression and impaired glutathione peroxidase 4 activity, which further activated ferroptosis and reduced proliferation of SHH-MB cells. Using an orthotopic mouse model, we observed that radiotherapy combined with silencing FANCD2 significantly inhibited the growth of SHH-MB cell-derived tumors in vivo. Our study revealed FANCD2 as a potential therapeutic target in SHH-MB and silencing FANCD2 could sensitize SHH-MB cells to radiotherapy via inducing ferroptosis. © 2024 The Pathological Society of Great Britain and Ireland.

Transcriptomic and proteomic strategies to reveal the mechanism of Gymnocypris przewalskii scale development.

BACKGROUND: Fish scales are typical products of biomineralization and play an important role in the adaptation of fish to their environment. The Gymnocypris przewalskii scales are highly specialized, with scales embedded in only specific parts of the dermis, such as the areas around the anal fin and branchiostegite, making G. przewalskii an ideal material for biomineralization research. In this study, we aimed to unveil genes and pathways controlling scale formation through an integrated analysis of both transcriptome and proteome, of which G. przewalskii tissues of the dorsal skin (no scales) and the rump side skin (with scales) were sequenced. The sequencing results were further combined with cellular experiments to clarify the relationship between genes and signaling pathways. RESULTS: The results indicated the following: (1) a total of 4,904 differentially expressed genes were screened out, including 3,294 upregulated genes and 1,610 downregulated genes (with a filtering threshold of |log2Fold-Change|> 1 and p-adjust < 0.05). The identified differentially expressed genes contained family members such as FGF, EDAR, Wnt10, and bmp. (2) A total of 535 differentially expressed proteins (DEPs) were filtered out from the proteome, with 204 DEPs downregulated and 331 DEPs upregulated (with a filtering threshold of |Fold-Change|> 1.5 and p < 0.05). (3) Integrated analyses of transcriptome and proteome revealed that emefp1, col1a1, col6a2, col16a1, krt8, and krt18 were important genes contributing to scale development and that PI3K-AKT was the most important signaling pathway involved. (4) With the use of the constructed G. przewalskii fibroblast cell line, emefp1, col1a1, col6a2, col16a1, krt8, and krt18 were confirmed to be positively regulated by the PI3K-AKT signaling pathway. CONCLUSION: This study provides experimental evidence for PI3K-AKT controlled scale development in G. przewalskii and would benefit further study on stress adaptation, scale biomineralization, and the development of skin appendages.

First Report of Colletotrichum godetiae Causing Anthracnose on Walnut (Juglans regia and Juglans sigillata) in China.

In August 2020, anthracnose lesions were observed on fruits of Juglans regia and J. sigillata in walnut orchards, in Yijun (Shaanxi Province) and Nanhua (Yunnan Province) counties, China. Symptoms on walnut fruits first appeared as small necrotic spots that rapidly enlarged into subcircular or irregular sunken black lesions (Fig. 1a, b). Sixty diseased walnut fruits (30 fruits of J. regia and J. sigillata, respectively) were randomly sampled from six orchards (10-15 ha each orchard, three orchards were selected in each county) with severe anthracnose (incidence rate of fruit anthracnose is over 60% in the orchard.) in two counties. Twenty-six single spore isolates were obtained from diseased fruits as described by Cai et al. (2009). After seven days, isolates formed grey to milky white colony with abundant aerial hyphae on the upper surface of colony, and milky white to light olive on the back of PDA (Fig. 1c). Conidiogenous cells were hyaline, smooth-walled, and cylindrical to clavate (Fig. 1d). Conidia were smooth-walled, aseptate, cylindrical to fusiform, with both ends acute or one end round and one end slightly acute (Fig. 1e), and ranged in size from 15.5-24.3×4.9-8.1 µm (n=30). Appressoria were brown to medium brown, clavate to elliptical, with the edge entire or undulate (Fig. 1f), and ranged in size from 8.0-27.6×4.7-13.7µm (n=30). The morphological characteristics of 26 isolates were similar to those of the species complex Colletotrichum acutatum (Damm et al. 2012). Six representative isolates were randomly selected (three isolates for each province) for molecular analysis. The ribosomal internal transcribed spacers (ITS) (White et al. 1990), beta-tubulin (TUB2) (Glass and Donaldson 1995), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Templeton et al.1992) and chitin synthase 1 (CHS-1) (Carbone and Kohn 1999) genes were amplified and sequenced. Sequences of 6 of 26 isolates were submitted to GenBank (Accession Nos: ITS: MT799938-MT799943, TUB: MT816321-MT816326, GAPDH:MT816327-MT816332, CHS-1: MT816333-816338). Multi-locus phylogenetic analyses revealed that six isolates clustered together with Colletotrichum godetiae ex-type culture isolates CBS133.44 and CBS130251, and the bootstrap support value was 100% (Fig.2). The pathogenicity of two representative isolates (CFCC54247 and CFCC54244) was tested using healthy fruits of the " J. regia cv. Xiangling" and " J. sigillata cv. Yangbi" varieties. Forty sterilized fruits (20 fruits were inoculated with CFCC54247, and 20 fruits with CFCC54244) were wounded by puncturing with a sterile needle through walnut pericarp and inoculated in the wound site with 10 µl of conidial suspension (106 conidia/ml) from seven day old colonies grown on PDA at 25℃. Twenty wounded fruits were inoculated with sterile water as control. Inoculated and control fruits were incubated in containers at 25℃ in a 12/12h light/dark cycle. The experiment was repeated three times. Anthracnose symptoms (Fig. 1g-h) were observed in all inoculated fruits after 12 days, whereas controls showed no symptoms. Fungal isolates from inoculated diseased fruits showed the same morphological and molecular characteristics as the isolates obtained in this study, confirming Koch's postulates. To our knowledge, this is the first report of C. godetiae causing anthracnose on the two walnut species in China. The result will be helpful for providing a basis for further research on the control of the disease.

Plastome phylogenomics provide new perspective into the phylogeny and evolution of Betulaceae (Fagales).

BACKGROUND: Betulaceae is a relatively small but morphologically diverse family, with many species having important economic and ecological values. Although plastome structure of Betulaceae has been reported sporadically, a comprehensive exploration for plastome evolution is still lacking. Besides, previous phylogenies had been constructed based on limited gene fragments, generating unrobust phylogenetic framework and hindering further studies on divergence ages, biogeography and character evolution. Here, 109 plastomes (sixteen newly assembled and 93 previously published) were subject to comparative genomic and phylogenomic analyses to reconstruct a robust phylogeny and trace the diversification history of Betulaceae. RESULTS: All Betulaceae plastomes were highly conserved in genome size, gene order, and structure, although specific variations such as gene loss and IR boundary shifts were revealed. Ten divergent hotspots, including five coding regions (Pi > 0.02) and five noncoding regions (Pi > 0.035), were identified as candidate DNA barcodes for phylogenetic analysis and species delimitation. Phylogenomic analyses yielded high-resolution topology that supported reciprocal monophyly between Betula and Alnus within Betuloideae, and successive divergence of Corylus, Ostryopsis, and Carpinus-Ostrya within Coryloideae. Incomplete lineage sorting and hybridization may be responsible for the mutual paraphyly between Ostrya and Carpinus. Betulaceae ancestors originated from East Asia during the upper Cretaceous; dispersals and subsequent vicariance accompanied by historical environment changes contributed to its diversification and intercontinental disjunction. Ancestral state reconstruction indicated the acquisition of many taxonomic characters was actually the results of parallel or reversal evolution. CONCLUSIONS: Our research represents the most comprehensive taxon-sampled and plastome-level phylogenetic inference for Betulaceae to date. The results clearly document global patterns of plastome structural evolution, and established a well-supported phylogeny of Betulaceae. The robust phylogenetic framework not only provides new insights into the intergeneric relationships, but also contributes to a perspective on the diversification history and evolution of the family.

Species divergence and phylogeography of Corylus heterophylla Fisch complex (Betulaceae): Inferred from molecular, climatic and morphological data.

Historical geo-climatic changes have shaped the geographical distributions and genetic diversity of numerous plant taxa in East Asia, which promote species divergence and ultimately speciation. Here, we integrated multiple approaches, including molecular phylogeography, ecological niche modeling, and morphological traits to examine the nucleotide diversity and interspecific divergence within Corylus heterophylla complex (C. heterophylla, C. kweichowensis, and C. yunnanensis). These three sibling taxa harbored similar high levels of nucleotide diversity at the species level. The molecular data (SCNG and cpDNA) unanimously supported the division of C. heterophylla complex into two major clades, with C. yunnanensis diverged earlier from the complex, whereas C. heterophylla and C. kweichowensis could hardly be separated. The split between the two clades (c. 12.89 Ma) coincided with the formation of Sichuan Basin in the middle Miocene, while the divergence among and within the five subclades (YUN1-YUN3, HK1-HK2) occurred from the late Miocene to the Pleistocene. C. heterophylla of northern China experienced glacial contraction and interglacial expansion during the Quaternary, whereas C. kweichowensis and C. yunnanensis of southern China presented population expansion even during the last glacial maximum. Despite of high levels of genetic admixture between C. heterophylla and C. kweichowensis, significant ecological and morphological discrepancy as well as incomplete geographic isolation indicated that adaptive evolution triggered by divergent selection may have played important roles in incipient ecological speciation.

MicroRNA-205-5p targets E2F1 to promote autophagy and inhibit pulmonary fibrosis in silicosis through impairing SKP2-mediated Beclin1 ubiquitination.

Silicosis is an occupational disease characterized by extensive pulmonary fibrosis, and the underlying pathological process remains uncertain. Herein, we explored the molecular mechanism by which microRNA-205-5p (miR-205-5p) affects the autophagy of alveolar macrophages (AMs) and pulmonary fibrosis in mice with silicosis through the E2F transcription factor 1 (E2F1)/S-phase kinase-associated protein 2 (SKP2)/Beclin1 axis. Alveolar macrophages (MH-S cells) were exposed to crystalline silica (CS) to develop an in vitro model, and mice were treated with CS to establish an in vivo model. Decreased Beclin1 and increased SKP2 and E2F1 were identified in mice with silicosis. We silenced or overexpressed miR-205-5p, E2F1, SKP2 and Beclin1 to investigate their potential roles in pulmonary fibrosis in vivo and autophagy in vitro. Recombinant adenovirus mRFP-GFP-LC3 was transduced into the MH-S cells to assay autophagic flow. Knocking down Beclin1 promoted pulmonary fibrosis and suppressed the autophagy. Co-immunoprecipitation and ubiquitination assays suggested that SKP2 induced K48-linked ubiquitination of Beclin1. Furthermore, chromatin immunoprecipitation-PCR revealed the site where E2F1 bound to the SKP2 promoter between 1638 bp and 1645 bp. As shown by dual-luciferase reporter gene assay, the transfection with miR-205-5p mimic inhibited the luciferase activity of the wild-type E2F1 3'untranslated region, suggesting that miR-205-5p targeted E2F1. Additionally, miR-205-5p overexpression increased autophagy and reduced the pulmonary fibrosis, while overexpression of E2F1 or SKP2 or inhibition of Beclin1 could annul this effect. The current study elucidated that miR-205-5p targeted E2F1, thereby inhibiting SKP2-mediated Beclin1 ubiquitination to promote macrophage autophagy and inhibit pulmonary fibrosis in mice with silicosis.

Could the EQ-5D-3L predict all-cause mortality in older Chinese? Evidence from a 5-year longitudinal study in eastern China.

PURPOSE: To assess the ability of the 3-level EQ-5D (i.e., EQ-5D-3L) in predicting all-cause mortality in older Chinese adults. METHODS: The data were from a 5-year longitudinal study, Weitang Geriatric Diseases Study, including 4579 community-dwelling older people in eastern China, with the mean age of 72.5 years at baseline and female being 52.0%. Three multivariable logistic regression models were adopted to assess the associations of the baseline EQ-5D data [i.e., the EQ-5D problems, EQ-5D-3L index score, and EQ-5D visual analog scale (VAS) score] with the 5-year all-cause mortality, adjusting for socio-demographic characteristics, and subsequently, health conditions and lifestyle habits. RESULTS: A total of 183 participants died over the 5-year study period. A larger proportion of the dead reported problems in physical dimensions (i.e., including three dimensions: mobility, self-care, and usual activities, p < 0.05 for all). The mean EQ-5D index score (0.928) and EQ-VAS score (79.7) of the living were higher than those of the dead (0.915 and 73.2, p < 0.05 for both). In multivariable logistic analyses, the EQ-5D health problems in the physical-related dimensions [odds ratio (OR) 2.16, p < 0.05] and the EQ-VAS score (OR: 0.97, p < 0.001) were associated with the 5-year all-cause mortality when adjusting for socio-demographic characteristics, health conditions, and lifestyle habits. CONCLUSIONS: It appears that the EQ-5D-3L could predict mortality in general older Chinese, which could be used to detect high-risk older individuals in China.

Habitual tea consumption and 5-year incident metabolic syndrome among older adults: a community-based cohort study.

BACKGROUND: The effect of tea consumption on metabolic syndrome (MetS) remains controversial. The objective of this study is to examine the prospective association of tea consumption with 5-year incident MetS among aged population in China. METHODS: This analysis included 3005 Chinese adults aged 60 years or older who were free of MetS at baseline examination. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III. Information regarding tea consumption was collected via an interviewer-administrated questionnaire. The prospective associations between tea consumption at baseline and 5-year incident MetS, as well as its individual components, were assessed by multiple logistic regression models. RESULTS: Of the 3005 participants free of MetS at baseline, 406 participants (cumulative incidence: 13.5%) developed MetS at the 5-year follow-up examination. In multiple logistic regressions, 5-year cumulative incidence of MetS was found to be higher in those who drank tea more than 5 times per week as compared with non-habitual drinkers (OR = 1.38, 95% CI: 1.05-1.82; P = 0.02). This relationship still existed in men (OR = 1.43, 95%CI: 1.00-2.01; P = 0.05) when stratified by gender. Among the five major components of MetS, low high-density lipoprotein cholesterol was observed in men, while high body mass index, elevated blood pressure and the presence of diabetes mellitus were significant in women. CONCLUSIONS: High-frequent tea consumption increased the risk of MetS among older Chinese adults. These findings may add novel knowledge to the current studies regarding the controversial effect of tea consumption on cardiovascular and metabolic health among the aged population.

Depressive symptom as a mediator of the influence of self-reported sleep quality on falls: a mediation analysis.

Objectives: It is well known that sleep quality was associated with falls. This study aimed to examine whether the presence of depressive symptoms mediate the association of self-reported sleep quality with falls.Methods: Data of community-based study including 4,579 adults aged 60 years or older were analyzed. Information regarding sleep quality and falls was self-reported by participants using pre-designed questionnaires. The nine-item Patient Health Questionnaire (PHQ-9) without the sleep item was used to assess the presence of depressive symptoms. A bootstrapping approach was performed to explore whether the relationship between self-reported sleep quality and falls was partially mediated by depressive symptoms. The mediator was considered significant if the 95% confidence interval (CI) did not include 0.Results: Older adults with poor sleep quality had higher odds of falls than their counterparts with normal sleep. In the equation regressed falls on self-reported sleep quality and PHQ-9 score, the association between self-reported sleep quality and falls disappeared. Depressive symptoms partially mediated the association between self-reported sleep quality and falls based on the significance of indirect effect (ß = 0.15, 95% bootstrap CI = 0.08, 0.22).Conclusions: The presence of depressive symptoms might partially mediate the association of self-reported sleep quality with falls among older adults.

Reduced Root Secretion of Valine in Rosa-Microbe Interaction Contributes to the Decreased Colonization of Pathogenic Agrobacterium tumefaciens.

Root exudates play a critical role in root-microbe interactions. Agrobacterium tumefaciens causes crown gall disease in multiple plant species, but rose root exudate-mediated inhibition of Agrobacterium in the rhizosphere is poorly understood. In this study, the influence of preinoculation with beneficial bacteria or pathogens on root exudates and subsequent colonization by A. tumefaciens was investigated in a split-root system. We found that preinoculation of rose plants in a split-root system with Bacillus velezensis CLA178 or A. tumefaciens C58 inhibited subsequent colonization by C58. Root secretion of valine had positive effects on the chemotaxis, biofilm formation, colonization of C58, and crown gall disease severity, but valine secretion decreased significantly when Rosa multiflora plants were preinoculated with CLA178 or C58. These results indicated that rose plants reduced root secretion of valine in response to microbial colonization, thereby reducing the colonization of Agrobacterium colonization and disease severity. This study provides new insights into the root exudate-mediated interactions of rose plants, B. velezensis, and A. tumefaciens and proposes a potential way to control crown gall disease.

Multilocus data reveal deep phylogenetic relationships and intercontinental biogeography of the Eurasian-North American genus Corylus (Betulaceae).

The evolutionary history of the genus Corylus, a tertiary disjunct lineage consisting of approximately 15-20 taxa with New and Old World distribution, has not been fully studied using molecular tools. In this research, we reconstructed comprehensive phylogenies of this genus using multiple datasets (genome-wide SNPs; complete chloroplast genomes; and nuclear ribosomal ITS sequences) based on detailed sampling of 17 Corylus species currently recognized. Divergence times were estimated using a fossil calibrated relaxed clock model, and ancestral area reconstruction were inferred using Bayesian binary MCMC (BBM) method and the dispersal-extinction-cladogenesis (DEC) model. Phylogenetic incongruences were detected from datasets, with nuclear SNP and ITS phylogenies supporting four major clades that correspond well with morphological traits, while chloroplast phylogeny revealed geographic partitioning. Recombination and introgressive hybridization played important roles in Corylus diversification. Molecular dating and biogeographical analyses unambiguously revealed that Corylus originated in Southwest China during the middle Eocene. The westward migration of Phyllochlamys (Clade C) and Colurnae (Clade D) and the uplift of Qinghai-Tibet Plateau drove the formation of European taxa, whereas the transoccanic migration crossing the Bering Land Bridge of Siphonochlamys (Clade B) and Phyllochlamys (Clade C) led to the occurrence of North American taxa. The topographic heterogeneity and climatic oscillations from Miocene to Pleistocene made East Asia the diversity center for Corylus. This study offers important insights into the phylogenetic relationships and biogeography history of the genus Corylus.

Tcf7l1 Acts as a Suppressor for the Self-Renewal of Liver Cancer Stem Cells and Is Regulated by IGF/MEK/ERK Signaling Independent of ß-Catenin.

Tcf7l1, which is a key effector molecule of the Wnt/ß-catenin signaling pathway, is highly expressed in various cancers, and it promotes tumor growth. In this study, we demonstrated that unlike its tumor-promoting effects in several other types of cancers, Tcf7l1 expression is downregulated in hepatocarcinoma compared with their adjacent nontumor counterparts. Underexpression of Tcf7l1 is correlated with poorer survival. In liver cancer stem cell (CSC) populations, Tcf7l1 expression is downregulated. Ectopic expression of Tcf7l1 attenuates the self-renewal abilities of liver CSCs. Mechanistically, Tcf7l1 regulates the self-renewal abilities of liver CSCs through transcriptional repression of the Nanog gene, and the effect is independent of ß-catenin. Moreover, we found that Tcf7l1 expression is controlled by extracellular insulin-like growth factor (IGF) signaling, and we demonstrated for the first time that IGF signaling stimulates Tcf7l1 phosphorylation and degradation through the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Overall, our results provide some new insights into how extracellular signals modulate the self-renewal of liver CSCs and highlight the inhibitory roles of Tcf7l1 in cancer. Stem Cells 2019;37:1389-1400.

Dyadobacter luteus sp. nov., isolated from rose rhizosphere soil.

A novel Gram-negative, aerobic, rod-shaped bacterium, RS19T, was isolated from rose rhizosphere soil. The strain was psychrophilic and showed good growth over a temperature range of 1-37 â„ƒ. Colonies on TSB agar were circular, smooth, mucoid, convex with clear edges and yellow. Phylogenetic analysis based on 16S rRNA gene sequences characterized RS19T in the genus Dyadobacter and showed that strain RS19T was most closely related to Dyadobacter psychrophilus CGMCC 1.8951T (97.4%) and Dyadobacter alkalitolerans CGMCC 1.8973T (97.1%). The average nucleotide identity values to the closest related species type strains were less than 84.0%. The DNA G + C content was 43.1 mol%, and the predominant respiratory menaquinone was MK-7. The major fatty acids were summed features 3 (C16:1ω7c and/or C16:1ω6c), iso-C15:0, C16:1ω5c and iso-C17:0 3-OH. Based on genotypic, phenotypic and chemotaxonomic data, strain RS19T is different from closely related species of the genus Dyadobacter. RS19T represents a novel species within the genus Dyadobacter, for which the name Dyadobacter luteus sp. nov. is proposed. The type strain is RS19T (= CGMCC 1.13719T = ACCC 60381T = JCM 32940T).

VLRs expression were significantly affected by complement C3 knockdown morphants in Lampetra morii.

The complement component 3 of the lamprey, a jawless vertebrate, functions as an opsonin during the phagocytosis of rabbit red cells. Furthermore, lamprey C3 may be activated and cleaved into C3b, which is attached to the surface of target cells in the cytolytic process. However, the mechanism mediating the biological function of C3 in the lamprey is unknown. To our knowledge, this study is the first to show that variable lymphocyte receptors (VLRs) expression were significantly affected by complement C3 knockdown morphants in Lampetra morii. We identified the C3 gene in the lamprey genome based on its orthologs, conserved synteny, functional domains, phylogenetic tree, and conserved motifs. Additionally, we determined the optimal infection concentration of Aeromonas hydrophila to perform immune stimulation experiments in the lamprey larvae. The quantitative real-time polymerase chain reaction and immunofluorescence analyses revealed that the expression of Lampetra morii C3 (lmC3) was significantly upregulated in the larvae infected with 107 CFU/mL of A. hydrophila. The lmC3 morphants (lmC3 MO) of lamprey larvae were generated by morpholino-mediated knockdown. The lmC3 MO larvae were highly susceptible to A. hydrophila infection, which indicated that lmC3 is critical in lamprey immune response. The expression of a selected panel of orthologous genes was comparatively analyzed in the infected wild type, infected lmC3 MO, infected control MO, uninfected wild type and uninfected lmC3 MO one-month-old ammocoete larvae. The knockdown of lmC3 strongly affected the expression of VLRA+/VLRB+/VLRC+-associated genes, which was also confirmed by immunohistochemical analysis. Thus, VLR expression were significantly affected by complement C3 knockdown morphants in Lampetra morii.

Lamprey VLRB participates in pathogen detection, VLRB/L-BLNK/L-NF-κB (B-like cells) signal transduction, and development.

In jawed vertebrates, B cell receptors (BCR) are primary pathogen detectors that activate downstream signaling pathways to express adaptive immune effectors. In jawless vertebrates, the variable lymphocyte receptors (VLR) B positive lymphocytes can express and secrete specific VLRB molecules in an analogous manner to that of immunoglobulins by B cells in jawed vertebrates. Our study is the first to demonstrate the possibility of incubation of fertilized eggs and artificial breeding of Lampetra morii larvae throughout their life cycle under laboratory condition. We also found that VLRB, lamprey B-cell linker (L-BLNK), and lamprey nuclear factor-kappa B (L-NF-κB) play key roles in early larval development. Aeromonas hydrophila was found to be a lethal pathogen of L. morii larvae causing rapid infection at a concentration of 107 cfu/mL qRT-PCR results revealed that gene expression levels of VLRB, L-BLNK, and L-NF-κB were up-regulated significantly. Ten-day infection trials showed that VLRB, L-BLNK, and L-NF-κB are crucial for lamprey immune response. Furthermore, the expression levels of L-BLNK and L-NF-κB were down-regulated drastically both at mRNA and protein levels after bacterial infection than in the naive group of VLRB morphants. A similar expression pattern of VLRB and L-BLNK was found in L-NF-κB morphants post bacterial infection. The results were strikingly different in the other two morphants. The VLRB and L-NF-κB expression levels were found to be down-regulated at mRNA and protein levels by less than 30% and 45%, respectively, in L-BLNK morphants compared to those in the naive group. These results indicate that L-BLNK and L-NF-κB might participate in VLRB-mediated immune response. Additionally, in VLRB morphants, the mRNA expression levels of some genes, especially the ones expressed in VLRB+ lymphocytes but not in VLRA+ lymphocytes, were found to be affected. Therefore, these findings of B-like lymphocytes in lamprey offer key evidence with regard to the evolution of adaptive immunity.

Comparing the performance of the EQ-5D-3 L and the EQ-5D-5 L in an elderly Chinese population.

BACKGROUND: This study was conducted to compare the validity and discriminative power of both the EQ-5D-3 L and EQ-5D-5 L in an elderly Chinese population with multiple chronic and acute conditions. METHODS: A total of 648 retired people from China (mean ± standard deviation: 73.3 ± 6.4 years; male: 55.7%) were recruited and randomized to complete the 3 L or 5 L questionnaire. The 3 L and 5 L were compared in terms of distribution properties, ceiling effects, informativity, validity and discriminatory performance. Convergent validity between the 3 L and 5 L was tested by spearman's rank-order correlation. Discriminatory power was conducted by relative efficiency as assessed by the F statistics. RESULTS: Most participants answered to "no problems" on both versions of EQ-5D. The 5 L trended towards a slightly lower ceiling compared with the 3 L. The Shannon index improved with the 5 L while the Shannon's Evenness index tended to be similar. Convergent validity was confirmed by the moderate to strong correlation for both 3 L and 5 L. Relative efficiency suggested that 5 L had a higher absolute discriminatory power than the 3 L version in terms of the presence conditions, especially for osteoporosis and metabolic syndrome. CONCLUSIONS: Both the 3 L and 5 L are demonstrated to be valid based HRQoL instruments in Chinese elderly population. The 5 L system may be preferable to the 3 L, as it demonstrated superior performance with respect to lower ceiling effect and better discriminatory power. Further research is needed to examine the responsiveness of the two EQ-5D instruments in this population.

Changes in health inequalities for patients with diabetes among middle-aged and elderly in China from 2011 to 2015.

BACKGROUND: The purpose of this paper is to measure income-related health inequality among middle-aged and elderly patients with diabetes in China from 2011 to 2015 and to investigate factors that might be related to this inequality. METHODS: The data for this study were obtained from the China Health and Retirement Longitudinal Study that was carried out in 2011, 2013 and 2015. In total, 48,519 Chinese middle-aged and elderly population were included (15,457 in 2011, 16,576 in 2013 and 16,486 in 2015). A principal component analysis was performed to measure asset-based economic status. The concentration index was used to measure income-related inequality in patients with diabetes. Additionally, by used generalized linear model, we decomposed the concentration index to identify factors that explained wealth-related inequality in patients with diabetes. RESULTS: The prevalence of self-reported diabetes among middle-aged and elderly Chinese was 5.61, 7.49 and 8.99% in 2011, 2013 and 2015, respectively. The concentration indices and 95% confidence intervals for diabetes were 0.1359 (0.0525-0.0597), 0.1207 (0.0709-0.0789), 0.1021 (0.0855-0.0942) in 2011, 2013, and 2015, respectively, which are indicative of inequality that favors the rich. The decomposition of the concentration index showed that residence (39.38%), BMI (31.16%), education (7.28%), and region (6.09%) had positive contributions to the measured inequality in diabetes in China in 2015. Age (- 29.93%) had a negative contribution to inequality. CONCLUSION: The findings confirm a health inequality in diabetes that favor the rich. Furthermore, the inequality declined from 2011 to 2015. We suggest that policy and intervention strategies should be developed to alleviate this health inequality, such as narrow the gap between urban and rural areas by improving the urban-rural medical insurance scheme, implementing strategies to enhance hygiene health education, control obesity rate.

Combined effect of three common lifestyle factors on cognitive impairment among older Chinese adults: a community-based, cross-sectional survey.

AIM: Lifestyle factors may influence cognitive function. Therefore, we compared the risk of cognitive impairment (COI) of all possible combinations of three lifestyle factors-tea consumption, physical activity, and siesta (afternoon nap or rest)-to the absence of any of these lifestyle factors. METHODS: This cross-sectional study consisted of 4579 community-dwelling Chinese individuals aged 60 years or older living in Suzhou. Among the subjects were 3634 participants with normal cognition and 945 who had been diagnosed with COI according to the Abbreviated Mental Test. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with a multivariate-adjusted model by logistic regression. RESULTS: Individually, tea consumption and physical activity significantly lowered the risk of COI to 0.66 (95%CI: 0.48-0.90) and 0.79 (95%CI: 0.65-0.96), respectively. In combination, physical activity and siesta reduced the risk of COI to the greatest extent (OR = 0.44, 95%CI: 0.31-0.64). Based on multivariate adjustment, almost all combinations of factors had a significant negative association with COI, but the combination of tea consumption and siesta had an irrelevant correlation with COI. All combinations of lifestyle factors had a lower OR than any single lifestyle factor among the correlations that were significant. CONCLUSION: Based on our findings, engaging in physical activity in combination with either or both of the other lifestyle factors was associated with a lower OR of having COI than adhering on a single factor in elderly Chinese people.

Determination of Clinical Cut-Off Values for Serum Cystatin C Levels to Predict Ischemic Stroke Risk.

BACKGROUND: The association between cystatin C and risk of ischemic stroke is inconsistent and the cut-off values of cystatin C are diverse in different articles. We aimed to investigate the association between cystatin C levels and the development of ischemic stroke and to explore the clinical cut-off values of serum cystatin C levels for ischemic stroke. METHODS: This prospective cohort study included 7658 participants from the China Health and Retirement Longitudinal Study who were free of cardiovascular diseases and cancer at baseline. A decision-tree model was used to find reasonable cut-off values for cystatin C levels. Logistic regression models were used to analyze the association between different levels of cystatin C and the risk of ischemic stroke. RESULTS: The whole cohort was divided into the following 3 groups according to the decision tree: group-low (<.901 mg/L), group-moderate (.901∼1.235 mg/L), and group-high (>1.235 mg/L). After 4 years of follow-up, we identified 156 cases of ischemic stroke. After adjusting for potential confounding factors, the odds ratios (95% confidence intervals) of ischemic stroke were 1.637 (1.048-2.556) for group-moderate and 2.326 (1.285-4.210) for group-high) compared with the low group of cystatin C. Subgroup analyses showed that the association between cystatin C levels and the incidence of ischemic stroke was more pronounced in males or old people than in females or young people. CONCLUSIONS: We found 2 suitable cut-off values for serum cystatin C levels and found that high levels of cystatin C were associated with an increased risk of ischemic stroke.

[Average blood glucose construction: a multi-level Bayes model approach and application].

OBJECTIVE: To explore the average blood glucose construction method based on the multi-level Bayes model and evaluate the example application. METHODS: We generate simulated data with multi-level Bayes model. Three methods were utilized to construct the average blood glucose at the same time, then we compared the result with each other. A cohort study method was used to select 12321 participants aged over 45 y who without stroke in a community in Suzhou and was followed up from 2011 to 2018, of which 53. 7% were male. Mean blood glucose calculated by the most accurate complete Bayesian method was divided into six groups. The Cox regression model was used to analyze the effect of mean blood glucose on the incidence of fatal stroke. RESULTS: 1000 times of simulation result showed that the average mean blood glucose estimation calculated by the complete Bayesian method was 0. 278, the average of blood glucose estimation was 0. 527 mmol/L, and the average correlation coefficient with the actual blood glucose was r=0. 898. During the follow-up period, 153 fatal strokes occurred. Association was found between the mean blood glucose and the risk of fatal stroke(P<0. 05). The average risk of blood glucose over 140 mg/dL was 2. 304 times that of 90-99 mg/dL(HR=2. 304, 95%CI 1. 151-4. 613) after the adjustment of effects. CONCLUSION: The complete Bayesian multi-level latent variable model can accurately estimate the average blood glucose.