Symptom structure of posttraumatic stress disorder in workplace trauma: A "distraction-avoidance" pattern.

BACKGROUND: Individuals who experience a workplace trauma are at a high risk of developing posttraumatic stress disorder (PTSD). Most of these people return to work soon after the trauma (i.e., experience early-stage natural exposure). This study aims to explore the response pattern of workers who have experienced a workplace trauma and early-stage natural exposure through network analysis and provide insights into the potential impact of early-stage natural exposure. METHODS: Our study included 278 workers directly experiencing the workplace explosion in the Tianjin Economic and Technological Development Zone. A partial correlation network analysis was used to explore the PTSD symptoms relationship and identify central symptoms. RESULTS: The results suggest that emotional numbness, difficulty in concentration, re-experiencing symptoms, and avoidance of thoughts are the most central symptoms, reflecting a "distraction-avoidance" pattern. CONCLUSIONS: The current study found that workers who experienced workplace trauma exhibited a "distraction-avoidance" pattern, which helps deepen our understanding of the PTSD network and leads to some suggestions on intervention measures.

Enhanced acetate utilization for value-added chemicals production in Yarrowia lipolytica by integration of metabolic engineering and microbial electrosynthesis.

The limited supply of reducing power restricts the efficient utilization of acetate in Yarrowia lipolytica. Here, microbial electrosynthesis (MES) system, enabling direct conversion of inward electrons to NAD(P)H, was used to improve the production of fatty alcohols from acetate based on pathway engineering. First, the conversion efficiency of acetate to acetyl-CoA was reinforced by heterogenous expression of ackA-pta genes. Second, a small amount of glucose was used as cosubstrate to activate the pentose phosphate pathway and promote intracellular reducing cofactors synthesis. Third, through the employment of MES system, the final fatty alcohols production of the engineered strain YLFL-11 reached 83.8 mg/g dry cell weight (DCW), which was 6.17-fold higher than the initial production of YLFL-2 in shake flask. Furthermore, these strategies were also applied for the elevation of lupeol and betulinic acid synthesis from acetate in Y. lipolytica, demonstrating that our work provides a practical solution for cofactor supply and the assimilation of inferior carbon sources.

Expression patterns and antifungal function study of KaSPI in Mythimna separata.

Kazal-type serine protease inhibitors (KaSPI) play important roles in insect growth, development, digestion, metabolism and immune defence. In this study, based on the transcriptome of Mythimna separata, the cDNA sequence of MsKaSPI with Kazal domain was uploaded to GenBank (MN931651). Spatial and temporal expression analysis showed that MsKaSPI was expressed at different developmental stages and different tissues, and it was induced by 20-hydroxyecdysone in third-instar larvae of M. separata. After 24 h infection by Beauveria bassiana, the expression level of MsKaSPI and the corresponding MsKaSPI content were significantly up-regulated, being 6.42-fold and 1.91-fold to the control group, respectively, while the activities of serine protease, trypsin and chymotrypsin were inhibited. After RNA interference interfered with MsKaSPI for 6 h, the expression decreased by 73.44%, the corresponding content of MsKaSPI protein decreased by 55.66% after 12 h, and the activities of serine protease and trypsin were significantly enhanced. Meanwhile, both the larval and pupal stages of M. separata were prolonged, the weights were reduced and the number of eggs per female decreased by 181. Beauveria bassiana infection also increased the mortality of MsKaSPI-silenced M. separata by 18.96%. These prove MsKaSPI can not only result in slow growth and low fecundity of M. separata by regulating the activity of related protease, but also participate in the resistance to pathogenic fungi by regulating the serine protease inhibitor content and the activities of related serine protease.

Construction of metal-organic framework-based multienzyme system for L-tert-leucine production.

Chiral compounds are important drug intermediates that play a critical role in human life. Herein, we report a facile method to prepare multi-enzyme nano-devices with high catalytic activity and stability. The self-assemble molecular binders SpyCatcher and SpyTag were fused with leucine dehydrogenase and glucose dehydrogenase to produce sc-LeuDH (SpyCatcher-fused leucine dehydrogenase) and GDH-st (SpyTag-fused glucose dehydrogenase), respectively. After assembling, the cross-linked enzymes LeuDH-GDH were formed. The crosslinking enzyme has good pH stability and temperature stability. The coenzyme cycle constant of LeuDH-GDH was always higher than that of free double enzymes. The yield of L-tert-leucine synthesis by LeuDH-GDH was 0.47 times higher than that by free LeuDH and GDH. To further improve the enzyme performance, the cross-linked LeuDH-GDH was immobilized on zeolite imidazolate framework-8 (ZIF-8) via bionic mineralization, forming LeuDH-GDH @ZIF-8. The created co-immobilized enzymes showed even better pH stability and temperature stability than the cross-linked enzymes, and LeuDH-GDH@ZIF-8 retains 70% relative conversion rate in the first four reuses. In addition, the yield of LeuDH-GDH@ZIF-8 was 0.62 times higher than that of LeuDH-GDH, and 1.38 times higher than that of free double enzyme system. This work provides a novel method for developing multi-enzyme nano-device, and the ease of operation of this method is appealing for the construction of other multi-enzymes @MOF systems for the applications in the kinds of complex environment.

Coupling riboflavin de novo biosynthesis and cytochrome expression for improving extracellular electron transfer efficiency in Shewanella oneidensis.

Shewanella oneidensis MR-1, as a model exoelectrogen with divergent extracellular electron transfer (EET) pathways, has been widely used in microbial fuel cells (MFCs). The electron transfer rate is largely determined by riboflavin (RF) and c-type cytochromes (c-Cyts). However, relatively low RF production and inappropriate amount of c-Cyts substantially impede the capacity of improving the EET rate. In this study, coupling of riboflavin de novo biosynthesis and c-Cyts expression was implemented to enhance the efficiency of EET in S. oneidensis. First, the upstream pathway of RF de novo biosynthesis was divided into four modules, and the expression level of 22 genes in above four modules was fine-tuned by employing promoters with different strengths. Among them, genes zwf*, glyA, and ybjU which exhibited optimal RF production were combinatorially overexpressed, leading to the enhancement of maximum output power density by 166%. Second, the diverse c-Cyts genes were overexpressed to match high RF production, and omcA was selected for further combination. Third, RF de novo biosynthesis and c-Cyts expression were combined, resulting in 2.34-fold higher power output than the parent strain. This modular and combinatorial manipulation strategy provides a generalized reference to advance versatile practical applications of electroactive microorganisms.

Effects of genotype and culture conditions on microspore embryogenesis in radish (Raphanus sativus L.).

Radish (Raphanus sativus L.), an important annual or biennial root vegetable crop, is widely cultivated in the world for its high nutritive value. Isolated microspore culture (IMC) is one of the most effective methods for rapid development of homozygous lines. Due to imperfection of the IMC technology system, it is particularly important to establish an efficient IMC system in radish. In this study, the effects of different factors on radish microspore embryogenesis were investigated with 23 genotypes. Buds with the largest population of late-uninucleate-stage microspores were most suitable for embryogenesis, with a ratio of petal length to anther length (P/A) in buds of about 3/4 ~ 1. Cold pretreatment was found to be genotype specific, and the highest microspore-derived embryoid (MDE) yield occurred for treatment of the heat shock of 48 h. In addition, the supplement of 0.75 g/L activated charcoal (AC) could increase the yield of embryoids. It was found that genotypes, bud size, as well as temperature treatments had significant effects on microspore embryogenesis. Furthermore, somatic embryogenesis-related kinase (SERK) genes were profiled by reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis, which indicated that they are involved in the process of MDE formation and plantlet regeneration. The ploidy of microspore-derived plants was identified by chromosome counting and flow cytometry, and the microspore-derived plants were further proved as homozygous plants through expressed sequence tags-simple sequence repeats (EST-SSR) and genetic-SSR markers. The results would facilitate generating the large-scale double haploid (DH) from various genotypes, and promoting further highly efficient genetic improvement in radish. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01312-w.

Decreased carboxylesterase expression associated with increased susceptibility to insecticide in Mythimna separata.

Carboxylesterases are one of the three major types of detoxification enzyme in insects. In this study, we screened 12 full-length carboxylesterase cDNA sequences from the oriental armyworm Mythimna separata; they were named MsCarE1-MsCarE12 and registered in GenBank with accession numbers MK440541-MK440552. Treatment of fourth instar larvae of M. separata with the LD50 of the insecticide chlorantraniliprole increased the expression levels of MsCarE3 and MsCarE4, while treatment with the LD50 of lambda-cyhalothrin significantly increased the expression levels of MsCarE5 and MsCarE10. Spatiotemporal expression detection showed that MsCarE3, MsCarE4, MsCarE5, and MsCarE10 were expressed at different developmental stages and in different tissues of M. separata and their expression levels were different. Induction using a high dose of chlorantraniliprole resulted in lower expression of MsCarE3 and MsCarE4. LD50 of lambda-cyhalothrin induced higher expression of MsCarE5 and MsCarE10, while LD70 induced higher MsCarE10 expression at 3, 6, and 12 h after treatment. RNA interference successfully inhibited the expression of MsCarE3, MsCarE4, MsCarE5, and MsCarE10, to different degrees at different time points. Silencing of MsCarE5, or MsCarE5 and MsCarE10 simultaneously changed carboxylesterase activity and increased the susceptibility of M. separata larvae to lambda-cyhalothrin. This study provides a new method to increase the insect susceptibility to insecticide.

Recent advances in microbial production of L-malic acid.

Over the last few decades, increasing concerns regarding fossil fuel depletion and excessive CO2 emissions have led to extensive fundamental studies and industrial trials regarding microbial chemical production. As an additive or precursor, L-malic acid has been shown to exhibit distinctive properties in the food, pharmaceutical, and daily chemical industries. L-malic acid is currently mainly fabricated through a fumarate hydratase-based biocatalytic conversion route, wherein petroleum-derived fumaric acid serves as a substrate. In this review, for the first time, we comprehensively describe the methods of malic acid strain transformation, raw material utilization, malic acid separation, etc., especially recent progress and remaining challenges for industrial applications. First, we summarize the various pathways involved in L-malic acid biosynthesis using different microorganisms. We also discuss several strain engineering strategies for improving the titer, yield, and productivity of L-malic acid. We illustrate the currently available alternatives for reducing production costs and the existing strategies for optimizing the fermentation process. Finally, we summarize the present challenges and future perspectives regarding the development of microbial L-malic acid production. KEY POINTS: • A range of wild-type, mutant, laboratory-evolved, and metabolically engineered strains which could produce L-malic acid were comprehensively described. • Alternative raw materials for reducing production costs and the existing strategies for optimizing the fermentation were sufficiently summarized. • The present challenges and future perspectives regarding the development of microbial L-malic acid production were elaboratively discussed.

The symptom network structure of posttraumatic stress disorder among Chinese firefighters.

BACKGROUND: The purpose of this study was to explore the core and driving symptoms of posttraumatic stress disorder (PTSD) of firefighters before and after rescue. Identifying core symptoms of PTSD can help clinicians to understand what may be relevant targets for treatment. METHODS: The study recruited 334 firefighters in a firefighter military school in September 2017 (T1). They were followed up 3 months later (T2), during which time they participated in real rescue activities. The network structure of DSM-5 PTSD was using regularized partial correlation models and a Bayesian approach computing directed acyclic graphs. RESULTS: The most central symptom both in T1 and T2 was negative emotional state. Irritable or anger emerged as a key driver of other symptoms in traumatized firefighters. CONCLUSIONS: Negative emotional state and irritable or anger might represent important symptoms within PTSD symptomatology and may offer key targets in PTSD treatment for firefighters.

A profile analysis of problematic smartphone usage among college students during coronavirus disease 2019: Relations with the impact of news reports.

The coronavirus disease 2019 (COVID-19) outbreak was the first pandemic to occur in a fully globalized society. The aims of the study were to explore the state of problematic smartphone use (PSU) and its risk factors during this incident. A total of 77,211 college students were surveyed online during the COVID-19 pandemic. Conducting latent profile analysis (LPA), we found the most support for a three-class model of subgroups: over-use group (17.3% of the sample), moderate-use group (54.8% of the sample), mild-use group (27.9% of the sample). The results of multinomial logistic regression show that college students who experienced an extreme negative impact from news reports were more likely to be included in the over-use group than in the mild-use group. These results providing insights that may help foster and develop appropriate and effective solutions to prevent PSU among college students during crises, such as reducing the coverage of negative news report. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03896-0.

Prevalence and predictors of posttraumatic stress disorder, depression and anxiety among hospitalized patients with coronavirus disease 2019 in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected more than 5 million people around the world and killed more than 300,000 people; thus, it has become a global public health emergency. Our objective was to investigate the mental health of hospitalized patients diagnosed with COVID-19. METHODS: The PTSD checklist for DSM-5 (PCL-5), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), Trauma Exposure Scale, abbreviated version of the Connor-Davidson Resilience Scale (CD-RISC-10), Perceived Social Support Scale (PSSS) and Demographic Questionnaire were used to examine posttraumatic stress disorder (PTSD), depression, anxiety, trauma exposure, resilience and perceived social support among 898 patients who were hospitalized after being diagnosed with COVID-19 in China. The data were analyzed with t tests, one-way ANOVA and multivariable logistic regression analysis. RESULTS: The results showed that the prevalence of PTSD, depression and anxiety was 13.2, 21.0 and 16.4%, respectively. Hospitalized patients who were more impacted by negative news reports, had greater exposure to traumatic experiences, and had lower levels of perceived social support reported higher PTSD, depression and anxiety. CONCLUSIONS: Effective professional mental health services should be designed to support the psychological wellbeing of hospitalized patients, especially those who have severe disease, are strongly affected by negative news and have high levels of exposure to trauma.

Predicting Posttraumatic Stress and Depression Symptoms Among Frontline Firefighters in China.

To investigate the prevalence and comorbidity rate of potential posttraumatic stress disorder (PTSD) and depression in frontline firefighters in China, as well as to analyze the related predictive factors for PTSD and depression, our study included 261 firefighters who completed assessments including the Demographic Data Forum, PTSD Checklist for DSM-5, Center for Epidemiological Studies Depression Scale, Chinese version of Perceived Stress Scale, and Perceived Social Support Scale. Among the participants, 1.9% and 11.9% were identified as having potential PTSD and depression, respectively. There was a 9.1% chance of comorbid PTSD among the depressed firefighters and a 60% chance of comorbid depression among the firefighters with PTSD. Perceived stress positively predicted both PTSD and depression; perceived social support negatively predicted both PTSD and depression. Whereas family exogenous support predicted both PTSD and depression, family endogenous support only predicted depression. In addition, PTSD was predicted by rank. Soldiers and sergeants demonstrated higher level of PTSD than officers. Future studies on mental health of firefighters should take factors like perceived stress, social support, and rank into consideration.

Professionals' responses to the introduction of AI innovations in radiology and their implications for future adoption: a qualitative study.

BACKGROUND: Artificial Intelligence (AI) innovations in radiology offer a potential solution to the increasing demand for imaging tests and the ongoing workforce crisis. Crucial to their adoption is the involvement of different professional groups, namely radiologists and radiographers, who work interdependently but whose perceptions and responses towards AI may differ. We aim to explore the knowledge, awareness and attitudes towards AI amongst professional groups in radiology, and to analyse the implications for the future adoption of these technologies into practice. METHODS: We conducted 18 semi-structured interviews with 12 radiologists and 6 radiographers from four breast units in National Health Services (NHS) organisations and one focus group with 8 radiographers from a fifth NHS breast unit, between 2018 and 2020. RESULTS: We found that radiographers and radiologists vary with respect to their awareness and knowledge around AI. Through their professional networks, conference attendance, and contacts with industry developers, radiologists receive more information and acquire more knowledge of the potential applications of AI. Radiographers instead rely more on localized personal networks for information. Our results also show that although both groups believe AI innovations offer a potential solution to workforce shortages, they differ significantly regarding the impact they believe it will have on their professional roles. Radiologists believe AI has the potential to take on more repetitive tasks and allow them to focus on more interesting and challenging work. They are less concerned that AI technology might constrain their professional role and autonomy. Radiographers showed greater concern about the potential impact that AI technology could have on their roles and skills development. They were less confident of their ability to respond positively to the potential risks and opportunities posed by AI technology. CONCLUSIONS: In summary, our findings suggest that professional responses to AI are linked to existing work roles, but are also mediated by differences in knowledge and attitudes attributable to inter-professional differences in status and identity. These findings question broad-brush assertions about the future deskilling impact of AI which neglect the need for AI innovations in healthcare to be integrated into existing work processes subject to high levels of professional autonomy.

Income-related inequality in distribution of health human resource among districts of Pakistan.

BACKGROUND: Solving inequality of health human resource (HHR) is one of the motives of Pakistan health policies, however, there is still exists a massive quantity of HHR inequality in almost every district of Pakistan. The main goal of this research is to scrutinize the disparity in allocation of human health resources among 114 regions of Pakistan from the year 2012 to 2016 and to expose the foundations and aspects of HHR inequality. METHODS: The data regarding this research has been obtained from Pakistan Statistical Bureau from the year 2012 to 2016. The statistics had also been collected from United Nation Development Program (UNDP) Pakistan 2017, Pakistan economic surveys, Ministry of finance Islamabad, Pakistan, Pakistan Social and Living standards Measurement (PSLM) Surveys from 2012 to 2016. The information incorporates district wise; the number of specialists and medical caretakers those are doctors and nurses, number of hospitals, number of beds, number of dispensaries, number of beds in dispensaries, urbanization, total estimated GNI per capita, infant mortality rate, geographical area, and population size. The concentration index is used to compute the extent of disparity in allocation of human health resources and decomposition analysis is also carried out to enumerate the contribution of each variable towards total inequality. Furthermore, the horizontal concentration was used to measure the participation of the need variable. RESULTS: 7. The consequent Concentration Indexes (CI) of the doctors and nurses for the year 2016 are 0.60 (95% CI= 0.42, 0.78) and 0.67 (95% CI= 0.42, 0.92) respectively. Decomposition of the concentration indexes exposed that the monetary status accounts are the leading percentage contributor in doctors disparity (77.5, 44.9, 30.6, - 11.6% and 13%) and population size (- 20.7,-10.5%, 4.6, 49.8, 19.7%). Furthermore, the monetary status formulates the superior contribution HHR disparity from nurses inequality (104.5, 75.1, 59.2, - 54.3%, - 40.1%), and population size (- 53.7, - 53.6%, - 36.3, 83.8, 65.3%). Moreover, after the identification of the need variable the Horizontal Concentration Index (HCI) values of doctors from the year 2012 to 2016 are 0.62, 0.64, 0.63, 0.62 and 0.61 and HCI of the nurses are 0.69, 0.70, 0.69, 0.68 and 0.67. CONCLUSION: The pro-rich disparity in allocation of HHR has been scrutinized from the year 2012 to 2016 among 114 districts of Pakistan. The hard concern of HHR disparity should be concentrated by the complete procedures from a multidisciplinary approach.

Changes in the Network Structure of Post-traumatic Stress Disorder Symptoms Among Earthquake Exposed Adolescents in China: A 2-Year Longitudinal Study.

Despite considerable studies focused on the symptoms of posttraumatic stress disorder (PTSD), little is understood about how symptoms of PTSD naturalistically change over time. Using network analyses approaches, the current study aimed to understand the nature of the association between PTSD symptoms at different time points among adolescents who experienced an earthquake. This study enrolled 900 youth survivors who completed 3 assessments with the Child PTSD Symptom Scale at 1 year, 1.5 years, and 2 years after the Wenchuan earthquake. A graphical Gaussian model (GGM) was used to investigate how symptom networks changed across these time points and to identify the symptoms that were the most central within the network. Results from GGM indicated that different symptoms were observed to have highest centrality at different time points. Feeling distant or cut off from others, avoid thoughts and feelings about the trauma, and feeling irritable or having angry outbursts appeared as the node with highest centrality at 1 year (T1), 1.5 years (T2), and 2 years (T3) post-earthquake, respectively.

Measuring spatial accessibility and within-province disparities in accessibility to county hospitals in Shaanxi Province of Western China based on web mapping navigation data.

BACKGROUND: The Chinese government proposed the "XIAO BING BU CHU CUN, DA BING BU CHU XIAN" initiative in 2016, which states the rate of health care service provided by county hospitals should reach 90% of overall health care service provision. The prerequisite for achieving this goal is that citizens should be able to access county hospitals' services conveniently and impartially. However, little research has been done on the actual levels of the spatial accessibility of citizens to county hospitals in Western China. Therefore, we aimed to measure the spatial accessibility to county hospitals for county residents and to identify any regional disparities in Shaanxi Province in Western China. METHODS: We implemented a novel method - involving utilizing navigation data from the AutoNavi web mapping system (knows as Gaode map in Chinese) - to assess the time and distance from villages and neighborhoods to the county hospitals. The navigation data were collected by request through an application-programming-interface using a web crawler (web data extraction tool) in Python. The shortest driving time and distance were extracted from the navigation data. The travel impedance to the nearest provider (TINP) indicator was used to measure spatial accessibility. RESULTS: The results show that county residents in Western China's Shaanxi Province have poor spatial accessibility to county hospitals. Only 68.8% of villages and neighborhoods are within 60 min travel time (based on driving mode) to a county hospital, while 13.4% of such villages and neighborhoods are beyond 90 min travel time. Moreover, a significant within-province disparity exists, with residents in the central area enjoying the best accessibility to county hospitals, while the northern and southern areas still need improvements in accessibility. CONCLUSIONS: Focused health resource planning is required to improve the spatial accessibility to county hospitals and to eliminate regional disparities. Further studies are called for to integrate the navigation data of web mapping systems with GIS methods to the measure spatial accessibility of health facilities in more complex contexts.

Chitin deacetylase: A potential target for Mythimna separata (Walker) control.

Chitin deacetylase (CDA) is a hydrolytic enzyme that modifies chitin into chitosan in the body of insects. In this study, we obtained a full-length complementary DNA sequence (MsCDA1) from the oriental armyworm Mythimna separata by high-throughput sequencing. MsCDA1 is 1,952 bp long and includes 1,620 bp open reading frame encoding 539 amino acids. Analysis by quantitative real time polymerase chain reaction showed that MsCDA1 expression was higher at the adult stage than at earlier developmental stages. MsCDA1 was expressed in all larval tissues examined, in which the highest expression level was found in the midgut. The RNA interference (RNAi) suppressed MsCDA1 expression levels at 12, 24, and 48 hr after injection of double-stranded RNA (1-4 µg per larva) specific to MsCDA1. Under RNAi condition, CDA enzyme activity was significantly reduced and changes an ultramicroscopic structure of M. separata peritrophic matrix especially in its microfibrillar organization exhibiting loose network. In contrast, the surface of the peritrophic matrix was relatively smooth and well organized at control or low RNAi conditions. Moreover, RNAi of MsCDA1 expression impaired larval growth and development, occasionally leading to larval death. These results demonstrate that MsCDA1 plays a crucial role in maintaining peritrophic matrix integrity in M. separata.

Higher Serum Neuropeptide Y Levels Are Associated with Metabolically Unhealthy Obesity in Obese Chinese Adults: A Cross-Sectional Study.

OBJECTIVE: Neuropeptide Y (NPY), an orexigenic peptide known to cause hyperphagia, has been involved in the occurrence and development of obesity. However, differences in the distribution of serum NPY levels in obese phenotypes (including metabolically unhealthy obesity (MUO) phenotype and metabolically healthy obesity (MHO) phenotype) and the association of NPY with MUO phenotype have not been unequivocally established. We therefore determined associations of serum NPY levels with MUO phenotype in obese Chinese adults. METHODS: A cross-sectional study was conducted from 400 obese adults in Hunan province, who underwent a health examination in the Second Xiangya Hospital, and 164 participants were finally enrolled in the study and divided into MHO and MUO groups. Serum NPY levels were examined; univariate and multivariate analyses as well as smooth curve fitting analyses were conducted to measure the association of NPY serum levels with the MUO phenotype. RESULTS: Serum NPY levels were significantly elevated in the MUO group compared with the MHO group ((667.69 ± 292.90) pg/mL vs. (478.89 ± 145.53) pg/mL, p < 0.001). A threshold and nonlinear association between serum NPY levels and MUO was found (p = 0.001). When serum NPY levels exceeded the turning point (471.5 pg/mL), each 10 pg/mL increment in the NPY serum level was significantly associated with an 18% increased odds ratio of MUO phenotype (OR: 1.18, 95% CI: 1.07-1.29, p = 0.0007) after adjusted for confounders. CONCLUSIONS: Higher NPY serum levels were positively correlated with MUO phenotype in obese Chinese adults.

Gencore: an efficient tool to generate consensus reads for error suppressing and duplicate removing of NGS data.

BACKGROUND: Removing duplicates might be considered as a well-resolved problem in next-generation sequencing (NGS) data processing domain. However, as NGS technology gains more recognition in clinical application, researchers start to pay more attention to its sequencing errors, and prefer to remove these errors while performing deduplication operations. Recently, a new technology called unique molecular identifier (UMI) has been developed to better identify sequencing reads derived from different DNA fragments. Most existing duplicate removing tools cannot handle the UMI-integrated data. Some modern tools can work with UMIs, but are usually slow and use too much memory. Furthermore, existing tools rarely report rich statistical results, which are very important for quality control and downstream analysis. These unmet requirements drove us to develop an ultra-fast, simple, little-weighted but powerful tool for duplicate removing and sequence error suppressing, with features of handling UMIs and reporting informative results. RESULTS: This paper presents an efficient tool gencore for duplicate removing and sequence error suppressing of NGS data. This tool clusters the mapped sequencing reads and merges reads in each cluster to generate one single consensus read. While the consensus read is generated, the random errors introduced by library construction and sequencing can be removed. This error-suppressing feature makes gencore very suitable for the application of detecting ultra-low frequency mutations from deep sequencing data. When unique molecular identifier (UMI) technology is applied, gencore can use them to identify the reads derived from same original DNA fragment. Gencore reports statistical results in both HTML and JSON formats. The HTML format report contains many interactive figures plotting statistical coverage and duplication information. The JSON format report contains all the statistical results, and is interpretable for downstream programs. CONCLUSIONS: Comparing to the conventional tools like Picard and SAMtools, gencore greatly reduces the output data's mapping mismatches, which are mostly caused by errors. Comparing to some new tools like UMI-Reducer and UMI-tools, gencore runs much faster, uses less memory, generates better consensus reads and provides simpler interfaces. To our best knowledge, gencore is the only duplicate removing tool that generates both informative HTML and JSON reports. This tool is available at: https://github.com/OpenGene/gencore.

A hypertension-associated mitochondrial DNA mutation introduces an m1G37 modification into tRNAMet, altering its structure and function.

Defective nucleotide modifications of mitochondrial tRNAs have been associated with several human diseases, but their pathophysiology remains poorly understood. In this report, we investigated the pathogenic molecular mechanism underlying a hypertension-associated 4435A→G mutation in mitochondrial tRNAMet The m.4435A→G mutation affected a highly conserved adenosine at position 37, 3' adjacent to the tRNA's anticodon, which is important for the fidelity of codon recognition and stabilization. We hypothesized that the m.4435A→G mutation introduced an m1G37 modification of tRNAMet, altering its structure and function. Primer extension and methylation activity assays indeed confirmed that the m.4435A→G mutation created a tRNA methyltransferase 5 (TRMT5)-catalyzed m1G37 modification of tRNAMet We found that this mutation altered the tRNAMet structure, indicated by an increased melting temperature and electrophoretic mobility of the mutated tRNA compared with the wildtype molecule. We demonstrated that cybrid cell lines carrying the m.4435A→G mutation exhibited significantly decreased efficiency in aminoacylation and steady-state levels of tRNAMet, as compared with those of control cybrids. The aberrant tRNAMet metabolism resulted in variable decreases in mitochondrial DNA (mtDNA)-encoded polypeptides in the mutant cybrids. Furthermore, we found that the m.4435A→G mutation caused respiratory deficiency, markedly diminished mitochondrial ATP levels and membrane potential, and increased the production of reactive oxygen species in mutant cybrids. These results demonstrated that an aberrant m1G37 modification of mitochondrial tRNAMet affected the structure and function of its tRNA and consequently altered mitochondrial function. Our findings provide critical insights into the pathophysiology of maternally inherited hypertension, which is manifested by the deficient tRNA nucleotide modification.