Paradoxical Mitophagy Regulation by PINK1 and TUFm.

Aberrant mitophagy has been implicated in a broad spectrum of disorders. PINK1, Parkin, and ubiquitin have pivotal roles in priming mitophagy. However, the entire regulatory landscape and the precise control mechanisms of mitophagy remain to be elucidated. Here, we uncover fundamental mitophagy regulation involving PINK1 and a non-canonical role of the mitochondrial Tu translation elongation factor (TUFm). The mitochondrion-cytosol dual-localized TUFm interacts with PINK1 biochemically and genetically, which is an evolutionarily conserved Parkin-independent route toward mitophagy. A PINK1-dependent TUFm phosphoswitch at Ser222 determines conversion from activating to suppressing mitophagy. PINK1 modulates differential translocation of TUFm because p-S222-TUFm is restricted predominantly to the cytosol, where it inhibits mitophagy by impeding Atg5-Atg12 formation. The self-antagonizing feature of PINK1/TUFm is critical for the robustness of mitophagy regulation, achieved by the unique kinetic parameters of p-S222-TUFm, p-S65-ubiquitin, and their common kinase PINK1. Our findings provide new mechanistic insights into mitophagy and mitophagy-associated disorders.

Impulsivity is a stable, measurable, and predictive psychological trait.

Impulsivity is a personality construct frequently employed to explain and predict important human behaviors. Major inconsistencies in its definition and measurement, however, have led some researchers to call for an outright rejection of impulsivity as a psychological construct. We address this highly unsatisfactory state with a large-scale, preregistered study (N = 1,676) in which each participant completed 48 measures of impulsivity derived from 10 self-report scales and 10 behavioral tasks and reported frequencies of seven impulsivity-related behaviors (e.g., impulsive buying and social media usage); a subsample (N = 196) then completed a retest session 3 mo later. We found that correlations between self-report measures were substantially higher than those between behavioral tasks and between self-report measures and behavioral tasks. Bifactor analysis of these measures exacted one general factor of impulsivity I, akin to the general intelligence factor g, and six specific factors. Factor I was related mainly to self-report measures, had high test-retest reliability, and could predict impulsivity-related behaviors better than existing measures. We further developed a scale named the adjustable impulsivity scale (AIMS) to measure I. AIMS possesses excellent psychometric properties that are largely retained in shorter versions and could predict impulsivity-related behaviors equally well as I. These findings collectively support impulsivity as a stable, measurable, and predictive trait, indicating that it may be too early to reject it as a valid and useful psychological construct. The bifactorial structure of impulsivity and AIMS, meanwhile, significantly advance the conceptualization and measurement of construct impulsivity.

Transcription factor encoding gene OsC1 regulates leaf sheath color through anthocyanidin metabolism in Oryza rufipogon and Oryza sativa.

Carbohydrates, proteins, lipids, minerals and vitamins are nutrient substances commonly seen in rice grains, but anthocyanidin, with benefit for plant growth and animal health, exists mainly in the common wild rice but hardly in the cultivated rice. To screen the rice germplasm with high intensity of anthocyanidins and identify the variations, we used metabolomics technique and detected significant different accumulation of anthocyanidins in common wild rice (Oryza rufipogon, with purple leaf sheath) and cultivated rice (Oryza sativa, with green leaf sheath). In this study, we identified and characterized a well-known MYB transcription factor, OsC1, through phenotypic (leaf sheath color) and metabolic (metabolite profiling) genome-wide association studies (pGWAS and mGWAS) in 160 common wild rice (O. rufipogon) and 151 cultivated (O. sativa) rice varieties. Transgenic experiments demonstrated that biosynthesis and accumulation of cyanidin-3-Galc, cyanidin 3-O-rutinoside and cyanidin O-syringic acid, as well as purple pigmentation in leaf sheath were regulated by OsC1. A total of 25 sequence variations of OsC1 constructed 16 functional haplotypes (higher accumulation of the three anthocyanidin types within purple leaf sheath) and 9 non-functional haplotypes (less accumulation of anthocyanidins within green leaf sheath). Three haplotypes of OsC1 were newly identified in our germplasm, which have potential values in functional genomics and molecular breeding of rice. Gene-to-metabolite analysis by mGWAS and pGWAS provides a useful and efficient tool for functional gene identification and omics-based crop genetic improvement.

Queen bee gut microbiota extends honeybee lifespan by inhibiting insulin signaling.

Queen and worker bees are natural models for aging research, as their lifespans vary considerably independent of genetic variation. Investigating the reasons why queens live longer than workers is of great significance for research on the universal processes of aging in animals. The gut microbiome has received attention as a vital regulator of host health, while its precise role in honeybee aging needs further investigation. The effects and mechanisms behind the relationship between gut microbiota and worker lifespan were measured by transplanting queen bee gut bacteria (QG) and worker bee gut bacteria (WG) into microbiota-free (MF) workers. The transplantation of QG to MF bees significantly extended the workers' lifespans compared with MF and WG bees. Untargeted metabolomics identified 49 lifespan-related differential metabolites, and Kyoto Encyclopedia of Genes and Genomes analysis of these revealed three lifespan-related metabolic pathways: insulin/insulin-like growth factor signaling, immune, and ketone body metabolism pathways. Further verification showed that QG inhibited the expression of insulin-like peptides (ILPs), and the expression of ILPs was lower in natural queens than in natural workers. QG transplantation also stimulated the expression of antioxidant genes and lowered oxidative damage products in natural queen bees. However, gut microbiota transplantation failed to mimic the immune properties and ketone body metabolism profiles of natural queens and workers. Concisely, QG could increase the antioxidant capacity to extend lifespan by inhibiting insulin signaling. These findings may help determine the mechanisms behind queen longevity and provide further insights into the role of gut symbionts. IMPORTANCE: Queen and worker bees share the same genetic background but have vastly different lifespans. The gut microbiome regulates host health, suggesting that differences in lifespan between queen and worker bees could be related to gut bacteria. Herein, we used an innovative method to transplant gut microbiota from adult queen or worker bees to microbiota-free bees. The transplantation of queen gut microbiota to microbiota-free bees extended their lifespan. Insulin/insulin-like growth factor signaling, a highly conserved metabolic pathway related to lifespan, displayed identical expression profiles in natural queen bees and microbiota-free bees transplanted with queen microbiota. This finding significantly expands our understanding of the relationships between intestinal bacteria, host health, and the biology of aging.

Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. RESULTS: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation. INTERPRETATION: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256.

Endosome mediated nucleocytoplasmic trafficking and endomembrane allocation is crucial to polyglutamine toxicity.

Aggregation of aberrant proteins is a common pathological hallmark in neurodegeneration such as polyglutamine (polyQ) and other repeat-expansion diseases. Here through overexpression of ataxin3 C-terminal polyQ expansion in Drosophila gut enterocytes, we generated an intestinal obstruction model of spinocerebellar ataxia type3 (SCA3) and reported a new role of nuclear-associated endosomes (NAEs)-the delivery of polyQ to the nucleoplasm. In this model, accompanied by the prominently increased RAB5-positive NAEs are abundant nucleoplasmic reticulum enriched with polyQ, abnormal nuclear envelope invagination, significantly reduced endoplasmic reticulum, indicating dysfunctional nucleocytoplasmic trafficking and impaired endomembrane organization. Consistently, Rab5 but not Rab7 RNAi further decreased polyQ-related NAEs, inhibited endomembrane disorganization, and alleviated disease model. Interestingly, autophagic proteins were enriched in polyQ-related NAEs and played non-canonical autophagic roles as genetic manipulation of autophagic molecules exhibited differential impacts on NAEs and SCA3 toxicity. Namely, the down-regulation of Atg1 or Atg12 mitigated while Atg5 RNAi aggravated the disease phenotypes both in Drosophila intestines and compound eyes. Our findings, therefore, provide new mechanistic insights and underscore the fundamental roles of endosome-centered nucleocytoplasmic trafficking and homeostatic endomembrane allocation in the pathogenesis of polyQ diseases.

A Drosophila Model Reveals the Potential Role for mtt in Retinal Disease.

Congenital stationary night blindness (CSNB) is a genetically heterogeneous inherited retinal disorder, caused by over 300 mutations in 17 different genes. While there are numerous fly models available for simulating ocular diseases, most are focused on mimicking retinitis pigmentosa (RP), with animal models specifically addressing CSNB limited to mammals. Here, we present a CSNB fly model associated with the mtt gene, utilizing RNA interference (RNAi) to silence the mtt gene in fly eyes (homologous to the mammalian GRM6 gene) and construct a CSNB model. Through this approach, we observed significant defects in the eye structure and function upon reducing mtt expression in fly eyes. This manifested as disruptions in the compound eye lens structure and reduced sensitivity to light responses. These results suggest a critical role for mtt in the function of fly adult eyes. Interestingly, we found that the mtt gene is not expressed in the photoreceptor neurons of adult flies but is localized to the inner lamina neurons. In summary, these results underscore the crucial involvement of mtt in fly retinal function, providing a framework for understanding the pathogenic mechanisms of CSNB and facilitating research into potential therapeutic interventions.

Perceptions and experience of rural older people in oral health management in China: a qualitative study.

BACKGROUND: To explore the perceptions and experience of oral health management among rural older people in China. METHODS: Qualitative methodologies were used in this study. Face-to-face semi-structured interviews were conducted. Thirteen older adults in rural areas were purposively sampled at two metropolitan hospitals in Hunan, China. The data were transcribed and thematically analyzed, and MAXQDA software was used to assist with coding. RESULTS: Three overarching major themes and ten sub­themes capturing the perceptions and experience of oral health management among rural older people were identified. Three themes emerged from the thematic analysis: oral health cognitive bias, poor management behaviors, and limited oral health services. Oral health management as a whole is negative, oral health behaviors are poor, oral health service utilization is limited. CONCLUSIONS: Based on these findings, there is great scope here for improving the current status of oral health for rural older people around awareness, behavior, and access. Oral health education, improved oral health services and primary oral health promotion are warranted.

Ame-miR-980-3p participates in autophagy-mediated midgut remodelling in Apis mellifera via targeting Atg2B.

Autophagy is a process that serves to degrade damaged proteins and organelles, thereby promoting cell homeostasis, differentiation, development and survival. Many miRNAs have been found to have regulatory roles in autophagy. In insects, it has been shown that autophagy is involved in hormone-regulated programmed cell death during metamorphic midgut remodelling. However, whether this is also true during the remodelling of the honey bee midgut is unclear. In the present study, we explored the relationship between autophagy and midgut remodelling and sought to identify miRNAs involved in this physiological process. We found that autophagy occurred during midgut remodelling and that the inhibition of autophagy resulted in midgut dysplasia in prepupae. Differentially expressed miRNAs enriched in the autophagy signalling pathway during midgut remodelling were identified by small RNA-seq. Ame-miR-980-3p, which targets the autophagy-related gene Atg2B, was screened out. Furthermore, abnormal expression of ame-miR-980-3p in the pupal stage led to the thinning of the midgut wall of newly emerged bees (NE). When ame-miR-980-3p expression was inhibited, the intestinal villi of NE bees became significantly shorter and sparse, and the lipid signal in the peritrophic matrix of Pb almost disappeared, indicating that the adult midgut was underdeveloped and the lipid absorption ability was weakened. Taken together, ame-miR-980-3p targeted Atg2B to participate in the regulation of midgut autophagy in the pupae, and the abnormal expression of ame-miR-980-3p would interfere with cell proliferation and death in the process of midgut remodelling, hinder the formation of adult midgut and eventually lead to adult midgut dysplasia and affect the lipid absorption function of the midgut in Apis mellifera.

Creation and gene expression analysis of a giant embryo rice mutant with high GABA content.

Gamma-amino butyric acid (GABA) is a natural non-protein amino acid involved in stress, signal transmission, carbon and nitrogen balance, and other physiological processes in plants. In the human body, GABA has the effects of lowering blood pressure, anti-aging, and activating the liver and kidneys. However, there are few studies on the molecular regulation mechanism of genes in the metabolic pathways of GABA during grain development of giant embryo rice with high GABA content. In this study, three glant embryo (ge) mutants of different embryo sizes were obtained by CRISPR/Cas9 knockout, and it was found that GABA, protein, crude fat, and various mineral contents of the ge mutants were significantly increased. RNA-seq and qRT-PCR analysis showed that in the GABA shunt and polyamine degradation pathways, the expression levels of most of the genes encoding enzymes promoting GABA accumulation were significantly upregulated in the ge-1 mutant, whereas, the expression levels of most of the genes encoding enzymes involved GABA degradation were significantly downregulated in the ge-1 mutant. This is most likely responsible for the significant increase in GABA content of the ge mutant. These results help reveal the molecular regulatory network of GABA metabolism in giant embryo rice and provide a theoretical basis for the study of its development mechanisms, which is conducive to the rapid cultivation of GABA-rich rice varieties, promoting human nutrition, and ensuring health. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01353-1.

Honey bee larval culture in vitro: gut emptying determines the transition from larva to prepupa and recombinant AccApidaecin improves antibacterial activity.

In vitro rearing of honey bee larvae is ideal for bioassay studies; no honey bee stable cell lines are available. Inconsistency of internal development staging of reared larvae and a susceptibility to contamination are common problems encountered. Standardized protocols on rearing larvae in vitro to make the larvae growth and development more similar to that of natural colonies are necessary to ensure the accuracy of experimental results and promote honey bee research as a model organism. Here, we concluded that when larval fasting weight was >160 mg, the time point of gut emptying can be defined as the critical point separating the larval and prepupal stages. In this way, we can conduct precise studies on the prepupal stage, such as organ remodeling during metamorphosis. Simultaneously, we further verified that recombinant AccApidaecin in genetic engineered bacteria added to the larval diet upregulated antibacterial peptide gene expression, and did not stimulate the stress response in larvae, nor did it affect the pupation rate or eclosion rate. This demonstrated that feeding recombinant AccApidaecin can enhance the individual antibacterial ability at the molecular level.

Characterization and Gene Mapping of an Open-Glume Oryza sativa L. Mutant.

Floral organ development determines agricultural productivity by affecting seed development, seed quality, and final yield. In this study, we described the novel ogl mutant in rice (Oryza sativa L.), which is characterized by an open-glume phenotype, increased pistil number, reduced stamen number, decreased seed setting rate, and smaller rice grains. Genetic analysis showed that the open-glume phenotype might be controlled by a recessive qualitative trait locus. Employing bulked segregant analysis (BSA), one candidate region was identified on rice chromosome 1. The glume opening phenotype cosegregated with SNP (Chr1:1522703), which was located at the start codon of one transcript of OsJAG, resulting in partial loss of OsJAG function. cDNA analysis revealed that OsJAG encodes two transcript variants. Compared to normal plants, the expression of OsJAG.1 was upregulated in open-glume plants. When investigating the glume phenotype, we found that the expression of genes related to floral development changed greatly in open-glume plants. Taken together, this work increases our understanding of the developmental role of OsJAG in rice floral development.

AmAtg2B-Mediated Lipophagy Regulates Lipolysis of Pupae in Apis mellifera.

Lipophagy plays an important role in regulating lipid metabolism in mammals. The exact function of autophagy-related protein 2 (Atg2) has been investigated in mammals, but research on the existence and functions of Atg2 in Apis mellifera (AmAtg2) is still limited. Here, autophagy occurred in honeybee pupae, which targeted lipid droplets (LDs) in fat body, namely lipophagy, which was verified by co-localization of LDs with microtubule-associated protein 1A/1B light chain 3 beta (LC3). Moreover, AmAtg2 homolog B (AmAtg2B) was expressed specifically in pupal fat body, which indicated that AmAtg2B might have special function in fat body. Further, AmAtg2B antibody neutralization and AmAtg2B knock-down were undertaken to verify the functions in pupae. Results showed that low expression of AmAtg2B at the protein and transcriptional levels led to lipophagy inhibition, which down-regulated the expression levels of proteins and genes related to lipolysis. Altogether, results in this study systematically revealed that AmAtg2B interfered with lipophagy and then caused abnormal lipolysis in the pupal stage.

Improvement of Rice Blast Resistance in TGMS Line HD9802S through Optimized Anther Culture and Molecular Marker-Assisted Selection.

Rice blast caused by Magnaporthe oryzae is one of the most serious rice diseases worldwide. The early indica rice thermosensitive genic male sterile (TGMS) line HD9802S has the characteristics of stable fertility, reproducibility, a high outcrossing rate, excellent rice quality, and strong combining ability. However, this line exhibits poor blast resistance and is highly susceptible to leaf and neck blasts. In this study, backcross introduction, molecular marker-assisted selection, gene chipping, anther culture, and resistance identification in the field were used to introduce the broad-spectrum blast-resistance gene R6 into HD9802S to improve its rice blast resistance. Six induction media were prepared by varying the content of each component in the culture medium. Murashige and Skoog's medium with 3 mg/L 2,4-dichlorophenoxyacetic acid, 2 mg/L 1-naphthaleneacetic acid, and 1 mg/L kinetin and N6 medium with 800 mg/L casein hydrolysate, 600 mg/L proline, and 500 mg/L glutamine could improve the callus induction rate and have a higher green seedling rate and a lower white seedling rate. Compared to HD9802S, two doubled haploid lines containing R6 with stable fertility showed significantly enhanced resistance to rice blast and no significant difference in spikelet number per panicle, 1000-grain weight, or grain shape. Our findings highlight a rapid and effective method for improving rice blast resistance in TGMS lines.

ZnS/CoS@C Derived from ZIF-8/67 Rhombohedral Dodecahedron Dispersed on Graphene as High-Performance Anode for Sodium-Ion Batteries.

Metal sulfides are highly promising anode materials for sodium-ion batteries due to their high theoretical capacity and ease of designing morphology and structure. In this study, a metal-organic framework (ZIF-8/67 dodecahedron) was used as a precursor due to its large specific surface area, adjustable pore structure, morphology, composition, and multiple active sites in electrochemical reactions. The ZIF-8/67/GO was synthesized using a water bath method by introducing graphene; the dispersibility of ZIF-8/67 was improved, the conductivity increased, and the volume expansion phenomenon that occurs during the electrochemical deintercalation of sodium was prevented. Furthermore, vulcanization was carried out to obtain ZnS/CoS@C/rGO composite materials, which were tested for their electrochemical properties. The results showed that the ZnS/CoS@C/rGO composite was successfully synthesized, with dodecahedrons dispersed in large graphene layers. It maintained a capacity of 414.8 mAh g-1 after cycling at a current density of 200 mA g-1 for 70 times, exhibiting stable rate performance with a reversible capacity of 308.0 mAh g-1 at a high current of 2 A g-1. The excellent rate performance of the composite is attributed to its partial pseudocapacitive contribution. The calculation of the diffusion coefficient of Na+ indicates that the rapid sodium ion migration rate of this composite material is also one of the reasons for its excellent performance. This study highlights the broad application prospects of metal-organic framework-derived metal sulfides as anode materials for sodium-ion batteries.

Rhizobial HmuSpSym as a heme-binding factor is required for optimal symbiosis between Mesorhizobium amorphae CCNWGS0123 and Robinia pseudoacacia.

Nitrogen-fixing root nodules are formed by symbiotic association of legume hosts with rhizobia in nitrogen-deprived soils. Successful symbiosis is regulated by signals from both legume hosts and their rhizobial partners. HmuS is a heme degrading factor widely distributed in bacteria, but little is known about the role of rhizobial hmuS in symbiosis with legumes. Here, we found that inactivation of hmuSpSym in the symbiotic plasmid of Mesorhizobium amorphae CCNWGS0123 disrupted rhizobial infection, primordium formation, and nitrogen fixation in symbiosis with Robinia pseudoacacia. Although there was no difference in bacteroids differentiation, infected plant cells were shrunken and bacteroids were disintegrated in nodules of plants infected by the ΔhmuSpSym mutant strain. The balance of defence reaction was also impaired in ΔhmuSpSym strain-infected root nodules. hmuSpSym was strongly expressed in the nitrogen-fixation zone of mature nodules. Furthermore, the HmuSpSym protein could bind to heme but not degrade it. Inactivation of hmuSpSym led to significantly decreased expression levels of oxygen-sensing related genes in nodules. In summary, hmuSpSym of M. amorphae CCNWGS0123 plays an essential role in nodule development and maintenance of bacteroid survival within R. pseudoacacia cells, possibly through heme-binding in symbiosis.

Arachis hypogaea L. from Acid Soils of Nanyang (China) Is Frequently Associated with Bradyrhizobium guangdongense and Occasionally with Bradyrhizobium ottawaense or Three Bradyrhizobium Genospecies.

Henan Province is a major area of peanut production in China but the rhizobia nodulating the crop in this region have not been described. A collection of 217 strains of peanut rhizobia was obtained from six field sites across four soil types in Henan Province, North China, by using peanut as a trap host under glasshouse conditions. The 217 strains separated into 8 distinct types on PCR-RFLP analysis of their IGS sequences. Phylogenetic analysis of the 16S rRNA, recA, atpD, and glnII genes of 11 representative strains of the 8 IGS types identified Bradyrhizobium guangdongense, B. ottawaense and three novel Bradyrhizobium genospecies. Bradyrhizobium guangdongense was dominant, accounting for 75.0% of the total isolates across the field sites while B. ottawaense covered 5.1% and the three novel Bradyrhizobium genospecies 4.1 to 8.8% of the total. The symbiosis-related nodA and nifH gene sequences were not congruent with the core genes on phylogenetic analysis and separated into three groups, two of which were similar to sequences of Bradyrhizobium spp. isolated from peanut in south-east China and the third identical to that of B. yuanmingense isolated from Lespedeza cuneata in northern China. A canonical correlation analysis between the distribution of IGS genotypes and soil physicochemical characteristics and climatic factors indicated that the occurrence of IGS types/species was mainly associated with soil pH and available phosphorus.

Efficient and risk-reduced genome editing using double nicks enhanced by bacterial recombination factors in multiple species.

Site-specific DNA double-strand breaks have been used to generate knock-in through the homology-dependent or -independent pathway. However, low efficiency and accompanying negative impacts such as undesirable indels or tumorigenic potential remain problematic. In this study, we present an enhanced reduced-risk genome editing strategy we named as NEO, which used either site-specific trans or cis double-nicking facilitated by four bacterial recombination factors (RecOFAR). In comparison to currently available approaches, NEO achieved higher knock-in (KI) germline transmission frequency (improving from zero to up to 10% efficiency with an average of 5-fold improvement for 8 loci) and 'cleaner' knock-in of long DNA fragments (up to 5.5 kb) into a variety of genome regions in zebrafish, mice and rats. Furthermore, NEO yielded up to 50% knock-in in monkey embryos and 20% relative integration efficiency in non-dividing primary human peripheral blood lymphocytes (hPBLCs). Remarkably, both on-target and off-target indels were effectively suppressed by NEO. NEO may also be used to introduce low-risk unrestricted point mutations effectively and precisely. Therefore, by balancing efficiency with safety and quality, the NEO method reported here shows substantial potential and improves the in vivo gene-editing strategies that have recently been developed.

Assessment of the oral health literacy and oral health behaviors among nurses in China: a cross-sectional study.

PURPOSE: Oral health is important for general health; nurses are expected to possess good oral health awareness and work together for public oral health promotion. The purpose of this study is to investigate oral health literacy (OHL)and oral health behaviors of nurses, and explore the association between oral health literacy with demographic variables and oral health behaviors. METHODS: A cross-sectional study in a tertiary hospital was conducted using a short-form Health Literacy in Dentistry-14 (HeLD-14) and a 16-items oral health behaviors questionnaire. Information about the subjects' demographic details including age, gender, place of residence, marital status, marital status, education level, monthly household income, working experience, etc. were collected. Independent sample t- test, One- way ANOVA, and multivariable regression were used to identify the association of oral health literacy with demographic variables and oral health behaviors. RESULTS: A total number of 317 nursing nurses participated in the survey, with a mean OHL score of 36.72, SD10.531, 21.8% were categorized as good, 34.1% medium and 44.2% poor oral health literacy; monthly household income, self-rated oral health, brushing time, use of fluoride toothpaste, and regular oral examination were signficantly associated with OHL scores. CONCLUSION: The overall oral health literacy of the nurse population is at a moderate to low level. These findings may help to map and design an oral health education intervention to improve oral health literacy amongst nurses, especially nurses with low monthly household income and poor self-assessed oral health status. Nursing administrators and nursing educators should pay more attention to the oral health status of the nurse population.

Extended RAS Analysis of the Phase III EPIC Trial: Irinotecan + Cetuximab Versus Irinotecan as Second-Line Treatment for Patients with Metastatic Colorectal Cancer.

BACKGROUND: The multicenter, open-label, randomized, phase III EPIC study (EMR 062202-025) investigated cetuximab plus irinotecan versus irinotecan in patients with epidermal growth factor receptor-detectable metastatic colorectal cancer (mCRC) that progressed on first-line fluoropyrimidine- and oxaliplatin-based chemotherapy; we report the outcomes of patients with RAS-wild-type (wt) disease. MATERIALS AND METHODS: Available DNA samples from RAS-unselected patients (n = 1,164 of 1,298 [89.7%]) were reanalyzed for RAS mutations using beads, emulsion, amplification, and magnetics. Baseline characteristics, efficacy, safety, and poststudy therapy were assessed. RAS-wt status was defined as a mutated RAS allele frequency of ≤5%, with all relevant alleles being analyzable. RESULTS: Baseline characteristics were comparable between the groups (n = 452 patients with RAS-wt mCRC; cetuximab plus irinotecan n = 231, irinotecan n = 221) and between the RAS-wt and RAS-unselected populations. In the cetuximab plus irinotecan versus irinotecan arms, median overall survival was 12.3 versus 12.0 months, median progression-free survival (PFS) was 5.4 versus 2.6 months, and objective response rate (ORR) was 29.4% versus 5.0%, respectively. Quality of life (QoL) was improved in the cetuximab plus irinotecan arm. Serious adverse events occurred in 45.4% (cetuximab plus irinotecan) and 42.4% (irinotecan) of patients. In total, 47.1% of patients in the irinotecan arm received subsequent cetuximab therapy. CONCLUSION: PFS, ORR, and QoL were improved with cetuximab plus irinotecan as a second-line treatment in patients with RAS-wt mCRC, confirming that cetuximab-based therapy is suitable in this population. Almost half of patients in the irinotecan arm received poststudy cetuximab, masking a potential overall survival benefit of cetuximab addition. IMPLICATIONS FOR PRACTICE: Cetuximab is approved for the treatment of RAS-wild-type metastatic colorectal cancer (mCRC). In this retrospective analysis of the phase III EPIC study (cetuximab plus irinotecan vs. irinotecan alone as second-line treatment in patients with RAS-unselected mCRC), the subgroup of patients with RAS-wild-type mCRC who received cetuximab plus irinotecan had improved progression-free survival, objective response rate, and quality of life compared with the RAS-unselected population. These findings suggest that cetuximab-based therapy is a suitable second-line treatment for patients with RAS-wild-type mCRC.