A Quantitative Proteome Map of the Human Body.

Determining protein levels in each tissue and how they compare with RNA levels is important for understanding human biology and disease as well as regulatory processes that control protein levels. We quantified the relative protein levels from over 12,000 genes across 32 normal human tissues. Tissue-specific or tissue-enriched proteins were identified and compared to transcriptome data. Many ubiquitous transcripts are found to encode tissue-specific proteins. Discordance of RNA and protein enrichment revealed potential sites of synthesis and action of secreted proteins. The tissue-specific distribution of proteins also provides an in-depth view of complex biological events that require the interplay of multiple tissues. Most importantly, our study demonstrated that protein tissue-enrichment information can explain phenotypes of genetic diseases, which cannot be obtained by transcript information alone. Overall, our results demonstrate how understanding protein levels can provide insights into regulation, secretome, metabolism, and human diseases.

Structure and topography of the synaptic V-ATPase-synaptophysin complex.

Synaptic vesicles are organelles with a precisely defined protein and lipid composition1,2, yet the molecular mechanisms for the biogenesis of synaptic vesicles are mainly unknown. Here we discovered a well-defined interface between the synaptic vesicle V-ATPase and synaptophysin by in situ cryo-electron tomography and single-particle cryo-electron microscopy of functional synaptic vesicles isolated from mouse brains3. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the proton gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters4,5. Synaptophysin6 and its paralogues synaptoporin7 and synaptogyrin8 belong to a family of abundant synaptic vesicle proteins whose function is still unclear. We performed structural and functional studies of synaptophysin-knockout mice, confirming the identity of synaptophysin as an interaction partner with the V-ATPase. Although there is little change in the conformation of the V-ATPase upon interaction with synaptophysin, the presence of synaptophysin in synaptic vesicles profoundly affects the copy number of V-ATPases. This effect on the topography of synaptic vesicles suggests that synaptophysin assists in their biogenesis. In support of this model, we observed that synaptophysin-knockout mice exhibit severe seizure susceptibility, suggesting an imbalance of neurotransmitter release as a physiological consequence of the absence of synaptophysin.

Structured elements drive extensive circular RNA translation.

The human genome encodes tens of thousands circular RNAs (circRNAs) with mostly unknown functions. Circular RNAs require internal ribosome entry sites (IRES) if they are to undergo translation without a 5' cap. Here, we develop a high-throughput screen to systematically discover RNA sequences that can direct circRNA translation in human cells. We identify more than 17,000 endogenous and synthetic sequences as candidate circRNA IRES. 18S rRNA complementarity and a structured RNA element positioned on the IRES are important for driving circRNA translation. Ribosome profiling and peptidomic analyses show extensive IRES-ribosome association, hundreds of circRNA-encoded proteins with tissue-specific distribution, and antigen presentation. We find that circFGFR1p, a protein encoded by circFGFR1 that is downregulated in cancer, functions as a negative regulator of FGFR1 oncoprotein to suppress cell growth during stress. Systematic identification of circRNA IRES elements may provide important links among circRNA regulation, biological function, and disease.

Transcriptome variation in human tissues revealed by long-read sequencing.

Regulation of transcript structure generates transcript diversity and plays an important role in human disease1-7. The advent of long-read sequencing technologies offers the opportunity to study the role of genetic variation in transcript structure8-16. In this Article, we present a large human long-read RNA-seq dataset using the Oxford Nanopore Technologies platform from 88 samples from Genotype-Tissue Expression (GTEx) tissues and cell lines, complementing the GTEx resource. We identified just over 70,000 novel transcripts for annotated genes, and validated the protein expression of 10% of novel transcripts. We developed a new computational package, LORALS, to analyse the genetic effects of rare and common variants on the transcriptome by allele-specific analysis of long reads. We characterized allele-specific expression and transcript structure events, providing new insights into the specific transcript alterations caused by common and rare genetic variants and highlighting the resolution gained from long-read data. We were able to perturb the transcript structure upon knockdown of PTBP1, an RNA binding protein that mediates splicing, thereby finding genetic regulatory effects that are modified by the cellular environment. Finally, we used this dataset to enhance variant interpretation and study rare variants leading to aberrant splicing patterns.

Personal omics profiling reveals dynamic molecular and medical phenotypes.

Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here, we present an integrative personal omics profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14 month period. Our iPOP analysis revealed various medical risks, including type 2 diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high-coverage genomic and transcriptomic data, which provide the basis of our iPOP, revealed extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and diseased states by connecting genomic information with additional dynamic omics activity.

INTS11-related neurodevelopmental disorder: a case report and literature review.

BACKGROUND: INTS11 is a critical catalytic component of the Integrator complex that regulates RNA polymerase II termination and modulates gene expression. Until recently, INTS11 mutations were associated with human neurodevelopmental disorders, characterized by global developmental and language delays, generalized hypotonia, and progressive brain atrophy. CASE: We report the case of a 2-year-old Chinese girl who presented with global developmental delay, generalized hypotonia, refractory epilepsy, craniofacial dysmorphism, and progressive brain atrophy. Novel variants were identified in exon 2 of INTS11 gene c.588_589del (p. Trp197AspfsTer2) and c.457_459del (p. Glu153del). CONCLUSION: We identified a compound heterozygous mutation in INTS11, a clinical feature consistent with two previous reports of the variants in human INTS11, but her recurrent seizures were more pronounced and refractory to most antiepileptic drugs and ketogenic diets.

Substrate-Independent Superhydrophobic Coating Capable of Photothermal-Induced Repairability for Multiple Damages Fabricated via Simple Blade Coating.

Repairable superhydrophobic surfaces have promising application potential in many fields. However, so far, it is still a challenge to develop a superhydrophobic surface with repairability for multiple types of damage through a simple method. In this paper, a repairable superhydrophobic coating was obtained on various substrates by blade-coating mixtures of polydimethylsiloxane (PDMS), polyvinylidene fluoride (PVDF), and multiwalled carbon nanotubes (MWCNTs) modified with dopamine (PDA) and octadecylamine (ODA). The obtained coating has a good liquid-repellent property with a water contact angle above 150° and a water sliding angle of ∼6° and possesses an excellent absorbance (∼97%) in the wavelength range of 250-2500 nm. Due to its high absorbance, the coating displays an outstanding photothermal effect with a temperature rise of ∼65 °C under irradiation by 1.0 kW/m2 of simulated sunlight. Furthermore, after being degraded by multiple stimuli, including plasma treatment, acid/alkali/oil immersion, sand impact, and the icing-thawing cycle, the coating can recover superhydrophobicity via sunlight irradiation, demonstrating the good photothermal-induced repairability of the coating. It can be expected that the good water-repellent property, photothermal effect, and repairability give this coating a promising prospect in practical applications.

Robust and Durable Superhydrophobic Coatings with Antipollution Flashover Performance via Silane-Modified Polyurea.

The inadequate hydrophobicity and the degradation in usage seriously hampered the applications of the existing antipollution flashover coatings. In this paper, a superhydrophobic polyurea coating with antipollution flashover ability was fabricated through chemically grafting the silica onto the chains of polyurea by utilizing silane coupling agent and hydrophobic modification. It is demonstrated that the coating exhibits outstanding antipollution flashover performances. Noteworthy, the surface pollution flashover voltage has been increased by 33.8% compared with the room temperature vulcanizing silicone rubber (RTV silicone rubber). In addition, the volume resistivity is above 1.0 × 1012 Ω·m, and the dielectric strength achieves to 28.85 kV/mm, which represents excellent insulating property. Furthermore, the superhydrophobic polyurea coating exhibits outstanding abrasion resistance, adhesion, acid-base resistance, and durability. As a result, it holds great promise for use in preventing pollution flashover in electrical insulators.

Comparative Analysis of Complete Mitochondrial Genomes of Five Chromodorididae Species (Nudibranchia:Doridina).

Mitochondrial genome is an important molecular marker for exploring the phylogenetic relationships of species and revealing molecular evolution. In the present study, 5 mitogenomes of Chromodorididae (Chromodoris lochi, Chromodoris colemani, Chromodoris elisabethina, Chromodoris annae and Hypselodoris whitei) were systemically investigated. The lengths of the mitogenomes sequences were 14248 bp, 14257 bp, 14252 bp, 14254 bp and 14856 bp, respectively. Most protein-coding genes (PCGs) were initiated with the common ATG codon and terminated with the TAA and TAG. We calculated Ka/Ks values for all 13 PCGs of Chromodorididae species, all ratios were less than 1, indicating selection by purification. Phylogenetic relationships were constructed by Bayesian inference (BI) and maximum likelihood (ML) methods based on all complete genomes of 50 species, primarily from the family Chromodorididae (Doridina) and 2 outgroups. This phylogenetic tree provided further additional references for the classification of the suborder Doridina. Gene rearrangement suggested a more conserved pattern of gene sequences in the superfamily Chromodoridoidea. These results and newly sequenced will contribute to a better understanding of Chromodorididae and provide reference for further phylogenetic studies.

Gene Rearrangements in the Mitochondrial Genome of Gonatopsis borealis and Onychoteuthis compacta Reveal Their Phylogenetic Implications for Oegopsida.

The complete mitochondrial genome provides crucial information for comprehending gene rearrangement, molecular evolution, and phylogenetic analysis. Here, we have determined the complete mitogenome sequence of Gonatopsis borealis and Onychoteuthis compacta for the first time. Their genome sizes were 20,148 bp and 20,491 bp, respectively, including 18 protein-coding genes, COI-COIII, ATP6, and ATP8 are duplicated, 23 transfer RNA genes, and 2 ribosomal RNA (rRNA) genes (12S and 16S rRNA). Specifically, the overall A+T content is 70.69% and 72.67%. It shows a significant AT bias. The whole mitogenomes indicate positive AT skew (0.070 and 0.062). Furthermore, the gene order has been rearranged within Oegopsida. The tandem duplication random loss model was determined as most likely to explain the observed gene rearrangements. Phylogenetic analysis was performed, and the result tree was found to be consistent with the morphological identification classification. Estimation of divergence time for 35 species showed that the main differentiation of Oegopsida occurred in 140.70 Mya. These results will help to better understand the gene rearrangements and evolution of G. borealis and O. compacta and lay a foundation for further phylogeny genetic studies of Oegopsida.

Life changes and symptoms of depression and anxiety among Chinese children and adolescents before, during, and after the COVID-19 pandemic lockdown: a combination of cross-sectional, longitudinal, and clustering studies.

The measures to prevent COVID-19 pandemic had caused significant life changes, which may have caused stress on the mental health of children and adolescents. We aimed to evaluate the short- and long-term effects of life changes on children's mental health in a large Chinese cohort. Survey-based life changes during COVID-19 lockdown were measured among 7,829 Chinese students at Grade 1-9, including social contacts, lifestyles and family financial status. Clustering analysis was applied to identify potential patterns of these changes. Depressive and anxiety symptoms were measured using the Center for Epidemiologic Studies Depression Scale and Screen for Child Anxiety Related Emotional Disorders. Logistic regression models were used to investigate the associations between these changes, their patterns and the presence of depression/anxiety symptoms using both cross-sectional and longitudinal designs. We found that the prevalence of depression and anxiety symptoms decreased during pandemic (34.6-32.6%). However, during and shortly after lockdown, students who reported negative impacts on their study, social and outside activities, and diet had increased risks of depressive/anxiety symptoms. Decreased electronic time and sugar-sweetened consumption, as well as family income decline and unemployment, were also associated with higher risks of these symptoms. Additionally, students with changed sleep time had increased depressive symptoms. These associations attenuated or disappeared one year later. Similar patterns were observed in clustering analysis, while only the group with severe impact on family financial status showed a sustained increase in depression symptoms. In summary, restrictive measures that changed children and adolescents' daily life during COVID-19 lockdown showed negative effects on their mental health, with some commonalities and distinctions patterns in the manifestation of depression and anxiety symptoms.

[Effect of Family Functioning on Adolescents' Internalizing and Externalizing Problem Behaviors: The Multiple Mediating Roles of Empathy and Emotional Competence]. / å®¶åº­åŠŸèƒ½å¯¹é’å°‘å¹´å† å¤–åŒ–é—®é¢˜è¡Œä¸ºçš„å½±å“ï¼šå ±æƒ å’Œæƒ ç»ªèƒ½åŠ›çš„å¤šé‡ä¸­ä»‹ä½œç”¨.

Objective: To examine the mediating role of empathy and emotional competence in the association between family functioning and internalizing and externalizing problem behaviors among adolescents in China. Methods: In this study, we used the data from the June-July 2022 survey of Chengdu Positive Child Development (CPCD) cohort. All respondents were 5th-9th graders from six primary or secondary schools in Chengdu. The Achenbach Child Behavior Checklist (CBCL), the Chinese Family Assessment Instrument (C-FAI), the empathy subscale of the Chinese version of the Interpersonal Reactivity Index (C-IRI), and the emotional competence (EC) subscale of the Chinese Positive Youth Development Scale (CPYD) were used to evaluate the respondents' internalizing and externalizing problem behaviors, family functioning, empathy, and emotional competence, respectively. The average score derived from the total score of a scale divided by the number of entries in each dimension was used as the final score of the scale. Independent samples t-tests or one-way analysis of variance (ANOVA) were performed to examine the differences in family functioning, empathy, emotional competence, and internalizing and externalizing problem behaviors across student groups with different demographic characteristics (sex, grade, and region). Pearson correlation analysis was conducted to examine the relationship between family functioning, empathy, emotional competence, and internalizing and externalizing problem behaviors. AMOS 24.0 was used to validate the hypothesized model and structural equation modeling was used to analyze the mediating effects of empathy and emotional competence between family functioning and internalizing and externalizing problem behaviors among adolescents. Results: A total of 3026 eligible participants were included, including 1548 (51.16%) male students and 1478 (48.84%) female students. Among the respondents, 798 (26.37%) were 5th graders, 738 (24.39%) were 6th graders, 567 (18.74%) were 7th graders, 614 (20.29%) were 8th graders, and 309 (10.21%) were 9th graders. In addition, 2064 (68.21%) of all respondents were from urban areas and 962 (31.79%) were from rural areas. The results of the difference analysis showed that the differences in adolescents' internalizing and externalizing problem behaviors were statistically significant between students of different grades (P=0.004), and that the differences in family functioning and empathy scores were also statistically significant between students of different grades (all P<0.001), whereas the differences in adolescents' internalizing and externalizing problem behaviors were not statistically significant between sexes and regions (P=0.919, 0.959). The results of correlation analysis showed that family functioning scores (the higher the score, the worse the family functioning) were significantly negatively correlated with empathy and emotional competence (r=-0.482, -0.432, P<0.01), and significantly positively correlated with internalizing and externalizing problem behaviors (r=0.220, P<0.01). Empathy was significantly positively correlated with emotional competence (r=0.402, P<0.01). Empathy and emotional competence were significantly negatively correlated with all the dimensions of internalizing and externalizing problem behaviors (r=-0.115, -0.305, P<0.01). Emotional competence partially mediated the relationship between family functioning and adolescents' internalizing and externalizing problem behaviors, with a mediation effect value being 0.042 (95% [confidence interval] CI: 0.031-0.057). Empathy and emotional competence had chain mediation effect between family functioning and adolescents' internalizing and externalizing problem behaviors, with the value of the mediation effect being 0.010 (95% CI: 0.007-0.014). Conclusion: Family functioning influences adolescents' internalizing and externalizing problem behaviors in a direct way and through the chain-mediating roles of empathy and emotional competence.

[Relationship Between Empathy and Depression in Adolescents: The Mediating Role of Family Functioning]. / é’å°‘å¹´å ±æƒ ä¸ŽæŠ‘éƒçš„å ³ç³»ï¼šå®¶åº­åŠŸèƒ½çš„ä¸­ä»‹ä½œç”¨.

Objective: To investigate the effect of empathy on depressive symptoms in adolescents and to explore the potential mediating role of family functioning in the effect of empathy on depressive symptoms. Methods: The 2022 cross-sectional data from the Chengdu Positive Child Development (CPCD) cohort were analyzed in the study. A survey was conducted in Chengdu in June 2022, involving 3020 students in grades 5-8 from three randomly selected stratified schools. The Interpersonal Reactivity Index (IRI-C), the Chinese Family Assessment Instrument (C-FAI), and the Center for Epidemiologic Studies Depression Scale for Children (CES-DC) were used in the survey. Chi-square test or one-way analysis of variance was performed to examine the differences in various demographic characteristics (sex, grade, region, and total monthly household income) between groups of respondents, as well as the differences in family functioning, empathy, and depression. Pearson correlation coefficient was used to examine the correlation between family functioning, empathy, and depressive symptoms. Structural equation modeling and SPSS PROCESS component Model 4 were used to analyze whether family functioning played a mediating role in the effect of empathy on depressive symptoms in adolescents. Results: The detection rate of depressive symptoms among survey respondents was 25.40%. The results of the difference analysis revealed significant differences in the detection rates of depressive symptoms among respondents of different grades, regions, and monthly household incomes (P<0.05). There was no significant difference in the detection rates of depressive symptoms between male and female students. There was a significant difference in the detection rate of depressive symptoms between respondents with different scores for family dysfunction and empathy ability (P<0.001). Correlation analysis results showed that empathy scores were negatively correlated with depression (r=-0.11, P<0.001), that family dysfunction was positively correlated with depression (r=0.29, P<0.001), and that empathy scores were negatively correlated with family functioning (r=-0.37, P<0.001). The mediating role of family dysfunction in the relationship between empathy and depressive symptoms was established, with the direct effect being 0.039 (95% confidence interval [CI]: 0.010-0.069, P<0.001) and the indirect effect value being -0.096 (95% CI: -0.115--0.079, P<0.001). The direct effect value accounted for 28.89% of the total effect value, while the mediation effect value accounted for 71.11% of the total effect value. Conclusion: The empathy ability of adolescents is correlated to depressive symptoms, and family functioning plays a mediating role between empathy and depressive symptoms in adolescents. It is suggested that adolescents' empathy ability and family functioning should be enhanced through multiple channels to reduce the occurrence of depressive symptoms.

Activation-Assisted High-Concentration Phosphorus-Doping to Enhance the Electrochemical Performance of Cobalt Carbonate Hydroxide Hydrate.

P-doping into metal oxides has been demonstrated as a valid avenue to ameliorate electrochemical performance because it can tune the electronic structures and increase the active sites for an electrochemical reaction. However, it usually results in a low P-doping concentration via the commonly used gas phosphorization method. In this work, an activation-assisted P-doping strategy was explored to significantly raise the P-doping concentration in cobalt carbonate hydroxide hydrate (CCHH). The activation treatment increased active sites for electrochemical reaction and endowed the sample with a high P content in the subsequent gas phosphorization process, thereby greatly enhancing the conductivity of the sample. Therefore, the final CCHH-A-P electrode exhibited a high capacitance of 6.62 F cm-2 at 5 mA cm-2 and good cyclic stability. In addition, the CCHH-A-P//CC ASC with CCHH-A-P as the positive electrode and carbon cloth as the negative electrode provided a high energy density of 0.25 mWh cm-2 at 4 mW cm-2 as well as excellent cycling performance with capacitance retention of 91.2% after 20,000 cycles. Our work shows an effective strategy to acquire Co-based materials with high-concentration P-doping that holds great potential in boosting the electrochemical performance of electrode materials via P-doping technology.

Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension.

Rationale: The role of neutrophils and their extracellular vesicles (EVs) in the pathogenesis of pulmonary arterial hypertension is unclear. Objectives: To relate functional abnormalities in pulmonary arterial hypertension neutrophils and their EVs to mechanisms uncovered by proteomic and transcriptomic profiling. Methods: Production of elastase, release of extracellular traps, adhesion, and migration were assessed in neutrophils from patients with pulmonary arterial hypertension and control subjects. Proteomic analyses were applied to explain functional perturbations, and transcriptomic data were used to find underlying mechanisms. CD66b-specific neutrophil EVs were isolated from plasma of patients with pulmonary arterial hypertension, and we determined whether they produce pulmonary hypertension in mice. Measurements and Main Results: Neutrophils from patients with pulmonary arterial hypertension produce and release increased neutrophil elastase, associated with enhanced extracellular traps. They exhibit reduced migration and increased adhesion attributed to elevated ß1-integrin and vinculin identified by proteomic analysis and previously linked to an antiviral response. This was substantiated by a transcriptomic IFN signature that we related to an increase in human endogenous retrovirus K envelope protein. Transfection of human endogenous retrovirus K envelope in a neutrophil cell line (HL-60) increases neutrophil elastase and IFN genes, whereas vinculin is increased by human endogenous retrovirus K deoxyuridine triphosphate diphosphatase that is elevated in patient plasma. Neutrophil EVs from patient plasma contain increased neutrophil elastase and human endogenous retrovirus K envelope and induce pulmonary hypertension in mice, mitigated by elafin, an elastase inhibitor. Conclusions: Elevated human endogenous retroviral elements and elastase link a neutrophil innate immune response to pulmonary arterial hypertension.

Oxycodone vs. tramadol in postoperative parent-controlled intravenous analgesia in children: a prospective, randomized, double-blinded, multiple-center clinical trial.

BACKGROUND: Management of acute postoperative pain is one of the major challenges in pediatric patients. Oral oxycodone has shown good pain relief in postoperative pain relief in children, but no studies have investigated intravenous oxycodone in this context. OBJECTIVE: whether oxycodone PCIA can provide adequate and safe postoperative pain relief, in comparison to tramadol as reference opioid drug. DESIGN: a randomized, double-blind, parallel, multi-center clinical trial. SETTING: five university medical centers and three teaching hospitals in China. PARTICIPANTS: patients aged 3-month-old to 6-year-old undergoing elective surgery under general anesthesia. INTERVENTION: patients were randomly allocated to either tramadol (n = 109) or oxycodone (n = 89) as main postoperative opioid analgesic. Tramadol or oxycodone were administered with a loading dose at the end of surgery (1 or 0.1 mg.kg-1, respectively), then with a parent-controlled intravenous device with fixed bolus doses only (0.5 or 0.05 mg.kg-1, respectively), and a 10-min lockout time. OUTCOMES: the primary outcome was adequate postoperative pain relief, defined as a face, legs, activity, cry, and consolability (FLACC) score < 4/10 in the post-anesthesia care unit (PACU), with no need for an alternative rescue analgesia. FLACC was measured 10 min after extubation then every 10 min until discharge from PACU. Analgesia was currently conducted with the boluses of either tramadol or oxycodone if FLACC was ≥ 3, up to three bolus doses, after what rescue alternative analgesia was administered. RESULTS: tramadol and oxycodone provided a similar level of adequate postoperative pain relief in PACU and in the wards. No significant differences were either noted for the raw FLACC scores, the bolus dose demand in PACU, the time between the first bolus dose and discharge from PACU, analgesic drug consumption, bolus times required in the wards, function activity score, or the parents' satisfaction. The main observed side effects in both groups were nausea and vomiting, with no difference between groups. However, patients in the oxycodone group showed less sedation levels and had a shorter stay in the PACU, compared with the tramadol group. CONCLUSIONS: an adequate postoperative analgesia can be achieved with intravenous oxycodone, this with less side effects than tramadol. It can therefore be a choice for postoperative pain relief in pediatric patients. TRIAL REGISTRATION: The study was registered at www.chictr.org.cn (Registration number: ChiCTR1800016372; date of first registration: 28/05/2018; updated date:06/01/2023).

[Effect of Family Environment on Non-Suicidal Self-Injury Among Middle School Students During the COVID-19 Epidemic: The Mediating Role of Depression].

Objective: To study the current status of non-suicidal self-injury (NSSI) incidents among middle school students in Chengdu during the COVID-19 epidemic and to explore the mechanism of action of depression on the relationship between family environment and NSSI. Methods: Data were obtained from the Chengdu Positive Child Development (CDPD) cohort. In June and July 2020, after primary and secondary schools were reopened after the closure due to the COVID-19 epidemic, on-site questionnaire surveys were conducted with the Deliberate Self-Harm Inventory (DSHI), the Chinese Family Assessment Instrument (C-FAI), and Center for Epidemiologic Studies Depression Scale for Children (CES-DC), thereby obtaining the data of 3595 middle school students. Two-sample t-test and χ 2 test were used to compare the incidence of NSSI among middle school students of different grades and genders, and the Model 58 test of the SPSS PROCESS component was used to analyze the mediating effect of gender-mediated depression. Results: 1) The incidence of NSSI among middle school students in Chengdu during the COVID-19 epidemic was 49.67%. The incidence of NSSI among ninth-graders (80.70%) was significantly higher than those of the eighth graders (33.82%) and seventh graders (32.32%), and the incidence of NSSI among female middle school students (54.75%) was significantly higher than that of male students (44.52%). 2) Family environment ( r=0.34, P<0.001) and depression ( r=0.50, P<0.001) were positively correlated with NSSI. 3) Depression partially mediated the effect of family environment on NSSI, with the mediating effect accounting for 64.64% of the total effect. Compared with that of male students, the positive predictive effect between family environment and depression and that between depression and NSSI in female middle school students were more significant. Conclusion: During the COVID-19 pandemic, middle school students in Chengdu had a high incidence of NSSI, which indicates that the family environment should be improved, more attention should be given to gender differences, and early screening and intervention for depression should be strengthened to reduce the incidence of NSSI.

AdaTiSS: a novel data-Adaptive robust method for identifying Tissue Specificity Scores.

MOTIVATION: Accurately detecting tissue specificity (TS) in genes helps researchers understand tissue functions at the molecular level. The Genotype-Tissue Expression project is one of the publicly available data resources, providing large-scale gene expressions across multiple tissue types. Multiple tissue comparisons and heterogeneous tissue expression make it challenging to accurately identify tissue specific gene expression. How to distinguish the inlier expression from the outlier expression becomes important to build the population level information and further quantify the TS. There still lacks a robust and data-adaptive TS method taking into account heterogeneities of the data. RESULTS: We found that the key to identify tissue specific gene expression is to properly define a concept of expression population. In a linear regression problem, we developed a novel data-adaptive robust estimation approach (AdaReg) based on density-power-weight under unknown outlier distribution and non-vanishing outlier proportion. The Gaussian-population mixture model was considered in the setting of identifying TS. We took into account heterogeneities of gene expression and applied the robust data-adaptive procedure to estimate the population parameters. With the well-estimated population parameters, we constructed the AdaTiSS algorithm.Our AdaTiSS profiled TS for each gene and each tissue, which standardized the gene expression in terms of TS. We provided a new robust and powerful tool to the literature of defining TS. AVAILABILITY AND IMPLEMENTATION: https://github.com/mwgrassgreen/AdaTiSS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RobNorm: model-based robust normalization method for labeled quantitative mass spectrometry proteomics data.

MOTIVATION: Data normalization is an important step in processing proteomics data generated in mass spectrometry experiments, which aims to reduce sample-level variation and facilitate comparisons of samples. Previously published methods for normalization primarily depend on the assumption that the distribution of protein expression is similar across all samples. However, this assumption fails when the protein expression data is generated from heterogenous samples, such as from various tissue types. This led us to develop a novel data-driven method for improved normalization to correct the systematic bias meanwhile maintaining underlying biological heterogeneity. RESULTS: To robustly correct the systematic bias, we used the density-power-weight method to down-weigh outliers and extended the one-dimensional robust fitting method described in the previous work to our structured data. We then constructed a robustness criterion and developed a new normalization algorithm, called RobNorm.In simulation studies and analysis of real data from the genotype-tissue expression project, we compared and evaluated the performance of RobNorm against other normalization methods. We found that the RobNorm approach exhibits the greatest reduction in systematic bias while maintaining across-tissue variation, especially for datasets from highly heterogeneous samples. AVAILABILITYAND IMPLEMENTATION: https://github.com/mwgrassgreen/RobNorm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Sugar transporter TaSTP3 activation by TaWRKY19/61/82 enhances stripe rust susceptibility in wheat.

Sugar efflux from host plants is essential for pathogen survival and proliferation. Sugar transporter-mediated redistribution of host sugar contributes to the outcomes of plant-pathogen interactions. However, few studies have focused on how sugar translocation is strategically manipulated during host colonization. To elucidate this question, the wheat sugar transport protein (STP) TaSTP3 responding to Puccinia striiformis f. sp. tritici (Pst) infection was characterized for sugar transport properties in Saccharomyces cerevisiae and its potential role during Pst infection by RNA interference and overexpression in wheat. In addition, the transcription factors regulating TaSTP3 expression were further determined. The results showed that TaSTP3 is localized to the plasma membrane and functions as a sugar transporter of hexose and sucrose. TaSTP3 confers enhanced wheat susceptibility to Pst, and overexpression of TaSTP3 resulted in increased sucrose accumulation and transcriptional suppression of defense-related genes. Furthermore, TaWRKY19, TaWRKY61 and TaWRKY82 were identified as positive transcriptional regulators of TaSTP3 expression. Our findings reveal that the Pst-induced sugar transporter TaSTP3 is transcriptionally activated by TaWRKY19/61/82 and facilitates wheat susceptibility to stripe rust possibly through elevated sucrose concentration, and suggest TaSTP3 as a strong target for engineering wheat resistance to stripe rust.