Assembly of novel sequences for Chinese domestic pigs reveals new genes and regulatory variants providing new insights into their diversity.

There is an increasing understanding that a reference genome representing an individual cannot capture all the gene repertoire of a species. Here, we conduct a population-scale missing sequences detection of Chinese domestic pigs using whole-genome sequencing data from 534 individuals. We identify 132.41 Mb of sequences absent in the reference assembly, including eight novel genes. In particular, the breeds spread in Chinese high-altitude regions perform significantly different frequencies of new sequences in promoters than other breeds. Furthermore, we dissect the role of non-coding variants and identify a novel sequence inserted in the 3'UTR of the FMO3 gene, which may be associated with the intramuscular fat phenotype. This novel sequence could be a candidate marker for meat quality. Our study provides a comprehensive overview of the missing sequences in Chinese domestic pigs and indicates that this dataset is a valuable resource for understanding the diversity and biology of pigs.

Genomic evidence for human-mediated introgressive hybridization and selection in the developed breed.

BACKGROUND: The pig (Sus Scrofa) is one of the oldest domesticated livestock species that has undergone extensive improvement through modern breeding. European breeds have advantages in lean meat development and highly-productive body type, whereas Asian breeds possess extraordinary fat deposition and reproductive performance. Consequently, Eurasian breeds have been extensively used to develop modern commercial breeds for fast-growing and high prolificacy. However, limited by the sequencing technology, the genome architecture of some nascent developed breeds and the human-mediated impact on their genomes are still unknown. RESULTS: Through whole-genome analysis of 178 individuals from an Asian locally developed pig breed, Beijing Black pig, and its two ancestors from two different continents, we found the pervasive inconsistent gene trees and species trees across the genome of Beijing Black pig, which suggests its introgressive hybrid origin. Interestingly, we discovered that this developed breed has more genetic relationships with European pigs and an unexpected introgression from Asian pigs to this breed, which indicated that human-mediated introgression could form the porcine genome architecture in a completely different type compared to native introgression. We identified 554 genomic regions occupied 63.30 Mb with signals of introgression from the Asian ancestry to Beijing Black pig, and the genes in these regions enriched in pathways associated with meat quality, fertility, and disease-resistant. Additionally, a proportion of 7.77% of genomic regions were recognized as regions that have been under selection. Moreover, combined with the results of a genome-wide association study for meat quality traits in the 1537 Beijing Black pig population, two important candidate genes related to meat quality traits were identified. DNAJC6 is related to intramuscular fat content and fat deposition, and RUFY4 is related to meat pH and tenderness. CONCLUSIONS: Our research provides insight for analyzing the origins of nascent developed breeds and genome-wide selection remaining in the developed breeds mediated by humans during modern breeding.

Integrated hybrid de novo assembly technologies to obtain high-quality pig genome using short and long reads.

With the rapid progress of sequencing technologies, various types of sequencing reads and assembly algorithms have been designed to construct genome assemblies. Although recent studies have attempted to evaluate the appropriate type of sequencing reads and algorithms for assembling high-quality genomes, it is still a challenge to set the correct combination for constructing animal genomes. Here, we present a comparative performance assessment of 14 assembly combinations-9 software programs with different short and long reads of Duroc pig. Based on the results of the optimization process for genome construction, we designed an integrated hybrid de novo assembly pipeline, HSCG, and constructed a draft genome for Duroc pig. Comparison between the new genome and Sus scrofa 11.1 revealed important breakpoints in two S. scrofa 11.1 genes. Our findings may provide new insights into the pan-genome analysis studies of agricultural animals, and the integrated assembly pipeline may serve as a guide for the assembly of other animal genomes.

Single-cell analysis reveals immune cellular components in odontogenic keratocysts.

OBJECTIVES: Various types of cells comprising a complex and diverse cell population are required for the biological activities of odontogenic keratocyst (OKC). Immune and non-immune cells collaborate via cytokine- or chemokine-mediated communication and direct cell-cell interactions. This study aimed to characterize the immune ecosystem and understand the potential chemotactic role of OKC fibroblasts in immune cell migration. MATERIALS AND METHODS: Mass cytometry of 41 markers was employed for the classification of OKC cells from six OKC samples. Immunofluorescence staining and single-cell RNA sequencing (GSE176351) were used for the detection of fibroblast subpopulations. Enzyme-linked immunosorbent assay and immunofluorescence staining were employed for chemokine detection in hypoxia- and/or HIF-1α inhibitor-treated OKC fibroblasts and tissues. Chemotaxis assay was employed to determine the chemotactic effect of fibroblasts via co-culture with peripheral blood mononuclear cells. A cell communication network was constructed based on the single-cell RNA sequencing data. RESULTS: The characterization of the immune cell types of OKC evidenced the enrichment of macrophages, neutrophils and B cells. The majority (41.5%) of fibroblast subsets consisted of chemokine ligand-enriched myofibroblasts. The activation of the HIF-1α signaling pathway in fibroblasts was associated with chemokine release. The chemokines released by OKC fibroblasts remarkably promoted the migration of peripheral blood mononuclear cells in the co-culture system. Close interactions between myofibroblasts and immune cells were validated by cell-cell interaction analysis. Increased RANKL expression was detected in OKC fibroblasts in the co-culture system with peripheral blood mononuclear cells. CONCLUSIONS: Our results provided deep insights into the immune ecosystem and highlighted the potential chemotactic effects of chemokine-enriched myofibroblasts within OKCs. The close interaction between immune cells and fibroblasts demonstrated in this study may be responsible for the osteoclastogenic effects of OKC fibroblasts.

Genome-wide association study reveals candidate genes for pollution excreta traits in pigs.

Excreta traits comprise a very important characteristic in breeding that have been neglected for a long time. With the growth of intensive pig farming, plenty of environment problems have been raised, and people have begun to pay attention to pig excreta behaviors from genetics and breeding perspectives. However, the genetic architecture of excreta traits remains unclear. To investigate the genetic architecture of excreta traits in pigs, eight excreta traits and feed conversion ratio (FCR) were analyzed in this study. We performed genome-wide association studies (GWASs) on 213 Yorkshire pigs and estimated genetic parameters for a total number of 290 pigs, comprising 213 Yorkshire, 52 Landrace and 25 Duroc. After analysis, eight and 22 genome-wide significant SNPs were detected for FCR and the eight excreta traits in single-trait GWASs separately, and 18 were detected in a multi-trait meta-analysis for excreta traits, six of which were detected in both the single-trait and the multi-trait GWAS. Eighty, 182 and 133 genes were detected within 1 Mb of the genome-wide significant SNPs for FCR, excreta traits and multi-trait meta-analysis, respectively. Five candidate genes (BCKDC, DBT, ANKRD7, SHPRH and HCRT) with biochemical and physiological effects relevant to feed efficiency and excreta traits might be interesting markers for future breeding. Meanwhile, functional enrichment analysis indicates that most of the significant pathways are associated with the glutathione catabolic process, DNA topological change and replication fork protection complex. This study reveals the architecture of excreta traits in commercial pigs and offers an opportunity for decreasing the pollution from excreta using genomic selection in pigs.

Transcriptome analysis reveals gene expression changes of pigs infected with non-lethal African swine fever virus.

African swine fever (ASF) is an important viral disease of swine caused by the African swine fever virus (ASFV), which threatens swine production profoundly. To better understand the gene expression changes when pig infected with ASFV, RNA sequencing was performed to characterize differentially expressed genes (DEGs) of six tissues from Kenya domestic pigs and Landrace × Yorkshire (L/Y) pigs infected with ASFV Kenya1033 in vivo. As results, a total of 209, 522, 34, 505, 634 and 138 DEGs (q-value < 0.05 and |Log2foldchange| values >2) were detected in the kidney, liver, mesenteric lymph node, peripheral blood mononuclear cell, submandibular lymph node and spleen, respectively. The expression profiles of DEGs shared in the multiple tissues illustrated variation in regulation function in the different tissues. Functional annotation analysis and interaction of proteins encoded by DEGs revealed that genes including IFIT1, IFITM1, MX1, OASL, ISG15, SAMHD1, IFINA1, S100A12 and S100A8 enriched in the immune and antivirus pathways were significantly changed when the hosts were infected with ASFV. The genes mentioned could play crucial roles in the process of the reaction to non-lethal ASF infection, which may will help to improve the ASF tolerance in the pig population through molecular breeding strategies.

Mitochondrial DNA enrichment reduced NUMT contamination in porcine NGS analyses.

Genetic associations between mitochondrial DNA (mtDNA) and economic traits have been widely reported for pigs, which indicate the importance of mtDNA. However, studies on mtDNA heteroplasmy in pigs are rare. Next generation sequencing (NGS) methodologies have emerged as a promising genomic approach for detection of mitochondrial heteroplasmy. Due to the short reads, flexible bioinformatic analyses and the contamination of nuclear mitochondrial sequences (NUMTs), NGS was expected to increase false-positive detection of heteroplasmy. In this study, Sanger sequencing was performed as a gold standard to detect heteroplasmy with a detection sensitivity of 5% in pigs and then one whole-genome sequencing method (WGS) and two mtDNA enrichment sequencing methods (Capture and LongPCR) were carried out. The aim of this study was to determine whether mitochondrial heteroplasmy identification from NGS data was affected by NUMTs. We find that WGS generated more false intra-individual polymorphisms and less mapping specificity than the two enrichment sequencing methods, suggesting NUMTs indeed led to false-positive mitochondrial heteroplasmies from NGS data. In addition, to accurately detect mitochondrial diversity, three commonly used tools-SAMtools, VarScan and GATK-with different parameter values were compared. VarScan achieved the best specificity and sensitivity when considering the base alignment quality re-computation and the minimum variant frequency of 0.25. It also suggested bioinformatic workflow interfere in the identification of mtDNA SNPs. In conclusion, intra-individual polymorphism in pig mitochondria from NGS data was confused with NUMTs, and mtDNA-specific enrichment is essential before high-throughput sequencing in the detection of mitochondrial genome sequences.

A Comparison Between Selective Lobar Bronchial Blockade and Main Bronchial Blockade in Pediatric Thoracoscopic Surgery: A Retrospective Cohort Study.

OBJECTIVE: The primary objective of this study was to assess the effect of selective lobar blockade on the risk of hypoxemia during one-lung ventilation in pediatric patients undergoing thoracoscopic surgery. DESIGN: This was a retrospective matched case-control cohort study. SETTING: The study was performed in a teaching hospital. PARTICIPANTS: A total of 60 pediatric patients who underwent thoracoscopic surgery in the authors' hospital from March 2020 to March 2021 were analyzed. INTERVENTIONS: The authors examined their electronic medical records and found 30 patients in whom selective lobar blockade was used. These patients then were matched to 30 other patients in whom routine main bronchial blockade was performed in the authors' center based on age, weight, sex, side of surgery, and type of surgery. MEASUREMENTS AND MAIN RESULTS: The inclusion criteria were four-fold: (1) pediatric patients with scheduled thoracoscopic resection of the middle and lower lobe lesions; (2) no obvious anesthesia or surgical contraindications; (3) American Society of Anesthesiologists class I to II; and (4) age younger than one year old. The exclusion criteria were as follows: (1) pediatric patients whose trachea was intubated with a size less than 3.0 mm; (2) a difficult airway; (3) changes in ventilation patterns during surgery; and (4) severe pneumonia and respiratory and circulatory system dysfunction. The following patient data were collected: (1) general clinical information; (2) mean arterial blood pressure, heart rate, central venous pressure, airway peak pressure (Ppeak), oxygenation index (PaO2/FIO2 ratio), and alveolar-arterial oxygen differential pressure (AaDO2) at different time points; that is, before one-lung ventilation (OLV) (T1), ten minutes after OLV (T2), and ten minutes after the end of OLV (T3); (3) degree of lung collapse ten minutes after OLV; (4) operative duration; and (5) the prevalence of hypoxemia, the number of adjustments required for intraoperative displacement of the bronchial blocker, and pulmonary atelectasis. A total of 135 patients were selected, and 60 pediatric patients (30 in group S and 30 in group R) were included in this study. There were no significant differences in age, sex, weight, general preoperative data, degree of lung collapse, or operative duration (p > 0.05). The perioperative hemodynamics between the two groups were not statistically significant (p > 0.05). The oxygenation index, AaDO2, and Ppeak were not significantly different between the two groups at the T1 time point (p > 0.05). However, the oxygenation index was higher, and AaDO2 and Ppeak were lower in group S than in group R at the T2 and T3 time points (p < 0.05). The incidence of atelectasis, the prevalence of hypoxemia, and the number of adjustments required for intraoperative displacement of the bronchial blocker in group S were lower than those in group R (p < 0.05). CONCLUSION: Selective lobar bronchial blockade, using a bronchial blocker in pediatric thoracoscopic surgery, may represent an alternative to excluding the main bronchial blockade for patients undergoing middle and lower lobe procedures, which may improve intraoperative oxygenation and reduce postoperative atelectasis.

Impact of High-Frequency Oscillatory Ventilation Combined With Volume Guarantee on Lung Inflammatory Response in Infants With Acute Respiratory Distress Syndrome After Congenital Heart Surgery: A Randomized Controlled Trial.

OBJECTIVES: Congenital heart disease (CHD) after cardiopulmonary bypass can cause systemic inflammation, and its degree is closely related to the incidence of acute respiratory distress syndrome (ARDS). The purpose of this study was to determine the effectiveness of high-frequency oscillatory ventilation (HFOV) combined with volume guarantee (VG) in reducing systemic inflammation in infants with ARDS after cardiopulmonary bypass for congenital heart surgery. DESIGN: A randomized controlled trial. SETTING: Single-center study in a tertiary teaching hospital. PARTICIPANTS: A total of 58 infants with ARDS after congenital heart surgery were eligible and were randomized to the HFOV (n = 29) or the HFOV-VG (n = 29) between January 2020 and January 2021. INTERVENTIONS: Tracheal aspirate samples for the measurement of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were obtained on days one, two, and three of HFOV or HFOV-VG ventilation. MEASUREMENTS AND MAIN RESULTS: The authors found a significantly increasing trend in the HFOV group mean values of IL-6, IL-8, and TNF-α (p < 0.05 on days two and three v day one), and IL-6, IL-8, and TNF-α levels were significantly higher on day three in the HFOV group versus the HFOV+VG group (p < 0.05). In addition, the incidences of hypocapnia and hypercapnia in infants supported with HFOV-VG were significantly lower (p < 0.05). Furthermore, the postoperative mechanical ventilation duration in the HFOV-VG group also was shorter than that in the HFOV group (p < 0.05). CONCLUSION: Compared with HFOV alone, HFOV-VG reduced proinflammatory systemic reactions after congenital cardiac surgery, decreased the incidences of hypercapnia and hypocapnia, and shortened the postoperative mechanical ventilation duration.

Condition notification assisted by virtual reality technology reduces the anxiety levels of parents of children with simple CHD: a prospective randomised controlled study.

PURPOSE: This study explored the effects of condition notification based on virtual reality technology on the anxiety levels of parents of children with simple CHD. METHODS: The subjects of the study were the parents of 60 children with simple CHD who were treated in our centre. The state anxiety scale was used to assess the anxiety status of the parents of the children before and after the condition notification in different ways (based on virtual reality explanations and written explanations). RESULTS: In this study, a total of 55 parents of children with CHD successfully completed the survey. At the time of admission, there was no significant difference in the state anxiety scale scores of the parents between the two groups. The anxiety status of the virtual reality group was relieved after the condition notification assisted by virtual reality technology, and there was a significant difference compared with the control group. CONCLUSION: Condition notification based on virtual reality technology can effectively alleviate the anxiety of parents of children with simple CHD, which is worthy of clinical application.

Application of the WeChat platform in midterm follow-up after surgical repair of ventricular septal defects in infants.

BACKGROUND: To explore the feasibility and superiority of applying the WeChat platform in a midterm follow-up of surgical repair for ventricular septal defects in infants. METHODS: Eighty-six infants with VSD who underwent surgical repair were divided into an outpatient follow-up group and a WeChat follow-up group. The clinical data, including complications, economic cost, time spent, loss to follow-up rate, and parents' satisfaction at the 3-month and 1-year follow-ups, were recorded and analysed. RESULTS: There was no significant difference in the incidence of post-operative complications between the two groups. Although the loss to follow-up rate in the WFU group was lower than that of the OFU group, the difference was not statistically significant. The economic cost and time spent in the 3 months and 1 year after discharge in the WFU group were significantly lower than those in the OFU group. One year after discharge, the PSQ-18 score of the WFU group was significantly higher than that of the OFU group. CONCLUSION: Compared with outpatient follow-up, the WeChat platform at the midterm follow-up after surgical repair of VSDs in infants has the advantages of saving time and economic costs and improves parents' satisfaction.

The effects of eye masks on post-operative sleep quality and pain in school-age children with CHD.

OBJECTIVE: This study aimed to explore the effects of eye masks on the sleep quality and pain of school-age children with CHD after surgery. METHODS: Forty school-age children with CHD who underwent open-heart surgery in the Cardiac Surgery Department of a provincial hospital in China from January 2020 to December 2020 were selected. The children were randomly divided into the experimental group (n = 20) and the control group (n = 20). Children in the control group were given routine sleep care, and the children in the experimental group were given a sleep intervention with eye masks for three nights following the removal of tracheal intubation. The Pittsburgh Sleep Quality Index was used to evaluate the sleep quality of the children. The Children's Pain Behaviour Scale was used to evaluate the pain of the children. RESULTS: After three nights of receiving the eye masks intervention, the sleep quality scores of the children in the experimental group were significantly lower than those of the control group, the difference was statistically significant (p < 0.05) and the sleep quality of the children in the experimental group was higher. The pain scores of the children in the experimental group were significantly lower than those of the children in the control group, the difference was statistically significant (p < 0.05), and the children in the experimental group suffered less post-operative pain. CONCLUSION: Eye masks are a simple, safe and economical intervention, that is beneficial for improving the post-operative sleep quality and relieving post-operative pain in school-age children with congenital heart disease.

Midazolam for conscious sedation in transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography.

OBJECTIVES: To investigate the safety and feasibility of midazolam for conscious sedation in transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography. METHODS: A retrospective analysis was performed on 55 patients who underwent transcatheter device closure of atrial septal defects from October, 2019 to May, 2020. All patients received intravenous midazolam and local anesthesia with lidocaine to maintain sedation. A group of previous patients with unpublished data who underwent the same procedure with general anesthesia was set as the control group. The relevant clinical parameters, the Ramsay sedation scores, the numerical rating scale, and the post-operative satisfaction questionnaire were recorded and analyzed. RESULTS: In the midazolam group, the success rate of atrial septal defect closure was 98.2%. Hemodynamic stability was observed during the procedure. None of the patients needed additional endotracheal intubation for general anesthesia. Compared with the control group, the midazolam group had no statistically significant differences in the Ramsay sedation score and numerical rating scale scores. Patients in the midazolam group experienced more post-operative satisfaction than those in the control group. CONCLUSIONS: Conscious sedation using midazolam is a safe and effective anesthetic technique for transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography.

Telehealth education improves parental care ability and postoperative nutritional status of infants after CHD surgery: A prospective randomized controlled study.

Objective: This study aimed to explore the effect of telehealth education on improving the parental care ability and postoperative nutritional status of infants after congenital heart disease surgery. Methods: A prospective randomized controlled study was conducted at a provincial maternal and child hospital in southeastern China. A total of 84 infants were enrolled in the study, with 42 infants in the intervention group and 42 infants in the control group. Results: Body weight, albumin, prealbumin, and hemoglobin of infants in the intervention group were significantly higher than those in the control group one month after discharge (P<0.05). The STRONGkids score of infants in the intervention group was significantly higher than that of those in the control group one month after discharge (P<0.05). The Family Caregiver Task Inventory score of infants in the intervention group was significantly lower than that of those in the control group one month after discharge (P<0.05). Conclusion: Performing telehealth education about home feeding and care guidance for parents of infants after congenital heart disease surgery can greatly improve parental care ability so that infants get better feeding and care, which can effectively improve the postoperative nutritional status of the infants.

[Effect of inhibiting miR-204 expression on the learning and memory abilities of neonatal rats with intrauterine growth restriction and related mechanism]. / 抑制miR-204è¡¨è¾¾å¯¹å®«å† å‘è‚²è¿Ÿç¼“æ–°ç”Ÿå¤§é¼ å­¦ä¹ è®°å¿†èƒ½åŠ›çš„å½±å“åŠç›¸å ³æœºåˆ¶.

OBJECTIVES: To investigate the effect of inhibiting miR-204 expression on the learning and memory abilities of neonatal rats with intrauterine growth restriction (IUGR) and related mechanism. METHODS: A rat model of IUGR was prepared by low-protein diet. The 3-day-old IUGR rats were divided into three groups: model, miRNA antagonist control and miR-204 antagonist, with 10 rats in each group. Ten normal neonatal rats served as the control group. Morris water maze test was used to measure the learning and memory abilities of the rats. Quantitative real-time PCR was used to measure the mRNA expression levels of miR-204 and brain-derived neurotrophic factor (BDNF) in the hippocampus. Nissl staining and TUNEL staining were used to observe the number of Nissl bodies and the apoptosis of cells in the hippocampus. Western blot was used to measure the expression levels of BDNF/TrkB signaling pathway-related proteins in the hippocampus. RESULTS: Compared with the control group, the model group had a significant increase in the escape latency and a significant reduction in the number of platform crossings (P<0.001). The model group also had significant increases in the apoptosis rate of cells and the expression level of miR-204 in hippocampal tissue (P<0.001), while the number of Nissl bodies, the mRNA expression level of BDNF, and the protein expression levels of BDNF, p-TrkB, and p-CREB in the model group were significantly reduced compared with the control group (P<0.001). After inhibition of the expression of miR-204, the number of Nissl bodies, the mRNA expression level of BDNF, and the protein expression levels of BDNF, p-TrkB, and p-CREB significantly increased, while the cell apoptosis rate and the expression level of miR-204 in the hippocampus significantly decreased. The escape latency was also reduced, while the number of platform crossings increased after inhibition of the expression of miR-204 (P<0.001). CONCLUSIONS: Inhibiting miR-204 can improve the learning and memory functions of neonatal rats with IUGR, possibly by targeted activation of the BDNF/TrkB signaling pathway.

Breed-specific reference sequence optimized mapping accuracy of NGS analyses for pigs.

BACKGROUND: Reference sequences play a vital role in next-generation sequencing (NGS), impacting mapping quality during genome analyses. However, reference genomes usually do not represent the full range of genetic diversity of a species as a result of geographical divergence and independent demographic events of different populations. For the mitochondrial genome (mitogenome), which occurs in high copy numbers in cells and is strictly maternally inherited, an optimal reference sequence has the potential to make mitogenome alignment both more accurate and more efficient. In this study, we used three different types of reference sequences for mitogenome mapping, i.e., the commonly used reference sequence (CU-ref), the breed-specific reference sequence (BS-ref) and the sample-specific reference sequence (SS-ref), respectively, and compared the accuracy of mitogenome alignment and SNP calling among them, for the purpose of proposing the optimal reference sequence for mitochondrial DNA (mtDNA) analyses of specific populations RESULTS: Four pigs, representing three different breeds, were high-throughput sequenced, subsequently mapping reads to the reference sequences mentioned above, resulting in a largest mapping ratio and a deepest coverage without increased running time when aligning reads to a BS-ref. Next, single nucleotide polymorphism (SNP) calling was carried out by 18 detection strategies with the three tools SAMtools, VarScan and GATK with different parameters, using the bam results mapping to BS-ref. The results showed that all eighteen strategies achieved the same high specificity and sensitivity, which suggested a high accuracy of mitogenome alignment by the BS-ref because of a low requirement for SNP calling tools and parameter choices. CONCLUSIONS: This study showed that different reference sequences representing different genetic relationships to sample reads influenced mitogenome alignment, with the breed-specific reference sequences being optimal for mitogenome analyses, which provides a refined processing perspective for NGS data.

Rapid epistatic mixed-model association studies by controlling multiple polygenic effects.

SUMMARY: We have developed a rapid mixed model algorithm for exhaustive genome-wide epistatic association analysis by controlling multiple polygenic effects. Our model can simultaneously handle additive by additive epistasis, dominance by dominance epistasis and additive by dominance epistasis, and account for intrasubject fluctuations due to individuals with repeated records. Furthermore, we suggest a simple but efficient approximate algorithm, which allows the examination of all pairwise interactions in a remarkably fast manner of linear with population size. Simulation studies are performed to investigate the properties of REMMAX. Application to publicly available yeast and human data has showed that our mixed model-based method has similar performance with simple linear model on computational efficiency. It took less than 40 h for the pairwise analysis of 5000 individuals genotyped with roughly 350 000 SNPs with five threads on Intel Xeon E5 2.6 GHz CPU. AVAILABILITY AND IMPLEMENTATION: Source codes are freely available at https://github.com/chaoning/GMAT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hippocampal miR-206-3p participates in the pathogenesis of depression via regulating the expression of BDNF.

As a widely-known neuropsychiatric disorder, the exact pathogenesis of depression remains elusive. MiRNA-206 (miR-206) is conventionally known as one of the myomiRs and has two forms: miR-206-3p and miR-206-5p. Recently, miR-206 has been demonstrated to regulate the biosynthesis of brain-derived neurotrophic factor (BDNF), a very popular target involved in depression and antidepressant responses. Here we assumed that miR-206 may play a role in depression, and various methods including the chronic social defeat stress (CSDS) model of depression, quantitative real-time reverse transcription PCR, western blotting, immuofluorescence and virus-mediated gene transfer were used together. It was found that CSDS robustly increased the level of miR-206-3p but not miR-206-5p in the hippocampus. Both genetic overexpression of hippocampal miR-206-3p and intranasal administration of AgomiR-206-3p induced not only notable depressive-like behaviors but also significantly decreased hippocampal BDNF signaling cascade and neurogenesis in naïve C57BL/6J mice. In contrast, both genetic knockdown of hippocampal miR-206-3p and intranasal administration of AntagomiR-206-3p produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, it was found that the antidepressant-like effects induced by miR-206-3p inhibition require the hippocampal BDNF-TrkB system. Taken together, hippocampal miR-206-3p participates in the pathogenesis of depression by regulating BDNF biosynthesis and is a feasible antidepressant target.

Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy.

BACKGROUND: Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). RESULTS: In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4ß1 and αLß2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. CONCLUSION: This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs.

Effect of WeChat follow-up education on breastfeeding efficiency of infants after congenital cardiac surgery and parents' satisfaction: A short-term follow-up study.

AIM: This study aimed to investigate the impact of WeChat follow-up education on infants' breastfeeding efficiency after congenital cardiac surgery and parents' satisfaction. METHODS: A prospective study was conducted in a provincial hospital in China. Sixty participants were divided into two groups: 30 participants in the study group received WeChat follow-up health education, and 30 participants in the control group received postoperative routine nursing education for infants after congenital cardiac surgery. The infants' breastfeeding efficiency, parents' satisfaction and relevant clinical data were recorded and analysed. RESULTS: After the WeChat follow-up intervention, the breastfeeding efficacy score, the parents' satisfaction score and the exclusive breastfeeding rate in the study group were significantly higher than those in the control group (P < 0.05). There was no significant difference in the incidence of feeding intolerance, abdominal distension, dyspeptic diarrhoea, weight gain or recurrent vomiting between the two groups during the 3-month follow-up period. CONCLUSION: WeChat education can improve infants' breastfeeding efficiency after congenital cardiac surgery and can improve parents' satisfaction and exclusive breastfeeding rate during the short-term follow-up period.