Genome-wide identification of resistance genes and response mechanism analysis of key gene knockout strain to catechol in Saccharomyces cerevisiae.

Engineering Saccharomyces cerevisiae for biodegradation and transformation of industrial toxic substances such as catechol (CA) has received widespread attention, but the low tolerance of S. cerevisiae to CA has limited its development. The exploration and modification of genes or pathways related to CA tolerance in S. cerevisiae is an effective way to further improve the utilization efficiency of CA. This study identified 36 genes associated with CA tolerance in S. cerevisiae through genome-wide identification and bioinformatics analysis and the ERG6 knockout strain (ERG6Δ) is the most sensitive to CA. Based on the omics analysis of ERG6Δ under CA stress, it was found that ERG6 knockout affects pathways such as intrinsic component of membrane and pentose phosphate pathway. In addition, the study revealed that 29 genes related to the cell wall-membrane system were up-regulated by more than twice, NADPH and NADP+ were increased by 2.48 and 4.41 times respectively, and spermidine and spermine were increased by 2.85 and 2.14 times, respectively, in ERG6Δ. Overall, the response of cell wall-membrane system, the accumulation of spermidine and NADPH, as well as the increased levels of metabolites in pentose phosphate pathway are important findings in improving the CA resistance. This study provides a theoretical basis for improving the tolerance of strains to CA and reducing the damage caused by CA to the ecological environment and human health.

Exposure to blue space surroundings and depressive symptoms in young Chinese adults: The mediating role of sleep.

OBJECTIVE: Existing evidence suggests that the natural environment can influence mental health. However, limited research has focused on the relationship between blue space and depressive symptoms in young adults. To investigate the association between blue space surroundings and depressive symptoms in young adults in China and explore the underlying mechanisms. METHODS: The study was conducted between September and November 2019, including 2,743 young adults from China. We assessed the exposure to blue space around participants' living environments during June, July, and August 2019 using the Modified Normalized Difference Water Index (MNDWI). Blue indexes were calculated for 300 m, 1000 m, and 3000 m circular buffer zones near residential environments. Logistic regression models were employed to explore the associations between blue space exposures (quartiles) and depressive symptoms, exploring potential mechanisms through structural equation modeling (SEM), while accounting for potential confounders. Stratification analysis was used to identify sensitive populations. RESULTS: Depressive symptoms were found in 148 (5.3%) of the 2,743 young adults in the study. We observed a negative correlation between depressive symptoms and average MNDWIs at participants' addresses (OR: 0.84; 95%CI: 0.72-0.98), within 300m (OR: 0.81; 95%CI: 0.70-0.95), 1000m (OR: 0.80; 95%CI: 0.69-0.93), and 3000m (OR:0.77; 95%CI: 0.66-0.89) buffer zones. Within the 1000m buffer zone, sleep was found to mediate 21% of the relationship between the presence of blue space and depressive symptoms. The stratified analysis revealed a stronger association between low MNDWI levels within the 1000m buffer zone and depressive symptoms in females (P < 0.05). Additionally, average MNDWI levels within the 3000m buffer zone were associated with depressive symptoms in both females and males. CONCLUSIONS: Blue space could improve depressive symptoms, particularly in females, with sleep playing a mediating role. Incorporating blue spaces into environmental planning is important for improving mental health.

Hypertrophic cardiomyopathy caused by a heterozygous variant in TTR gene: A case report.

RATIONALE: We report a rare case of hypertrophic cardiomyopathy (HCM) caused by a heterozygous variant in TTR gene. PATIENT CONCERNS: The proband had been vomiting without obvious inducement since the age of 27, accompanied by the expulsion of stomach contents. At the age of 28, she began to suddenly syncope. DIAGNOSIS: Cardiac magnetic resonance showed thickening of the right ventricular lateral wall and ventricular septum. The left ventricular diastolic function was limited. Targeted Sanger sequencing validates the presence of mutation p.Leu75Pro in TTR gene. INTERVENTIONS AND OUTCOMES: After admission to hospital for syncope, she was given metoprolol tablets 25 mg bid, spironolactone tablets 20 mg qd, and trimetazidine 20 mg tid. Her symptoms improved after taking the medicine. LESSONS: The results of this case show that HCM caused by TTR mutation is not easy to be identified and treatment is easy to be delayed. Therefore, high-risk patients with amyloidosis should be evaluated as soon as possible. Timely diagnosis of HCM caused by TTR mutation before irreversible organ damage is essential for proper treatment and better outcomes.

SPAG6 c.900 T>C affects boar semen quality and blood-testis barrier function by creating a new splice acceptor site.

Sperm associated antigen 6 (SPAG6) acts as a scaffolding protein in the center of the flagellar axoneme and has an impact on the maturation of the motility of mammalian sperm flagella and the maintenance of sperm structure. In our previous research, SPAG6 c.900 T>C in exon 7 and exon 7 skipped transcript was identified by analyzing RNA-seq data of testicular tissues from 60 day (sexually immature) and 180 day (sexually mature) Large White boars. Herein, we found porcine SPAG6 c.900 T>C to be associated with semen quality traits in Duroc, Large White and Landrace pigs. SPAG6 c.900 C can generate a new splice acceptor site, inhibit the occurrence of SPAG6 exon 7 skipping to a certain extent, thereby promote the growth of Sertoli cells and maintain the normal blood-testis barrier function. This study provides new insights into the molecular regulation of spermatogenesis and a new genetic marker for the improvement of semen quality in pigs.

Fine mapping of the grain chalkiness quantitative trait locus qCGP6 reveals the involvement of Wx in grain chalkiness formation.

Grain chalkiness is an important index of rice appearance quality and is negatively associated with rice processing and eating quality. However, the genetic mechanism underlying chalkiness formation is largely unknown. To identify the genetic basis of chalkiness, 410 recombinant inbred lines (RILs) derived from two representative indica rice varieties, Shuhui498 (R498) and Yihui3551 (R3551), were used to discover quantitative trait loci (QTLs). The two parental lines and RILs were grown in three locations in China under three controlled fertilizer application levels. Analyses indicated that chalkiness was significantly affected by genotype, the environment, and the interaction between the two, and that heritability was high. Several QTLs were isolated, including the two stable QTLs qCGP6 and qCGP8. Fine mapping and candidate gene verification of qCGP6 showed that Wx may play a key role in chalkiness formation. Chromosomal segment substitution lines (CSSLs) and near-isogenic lines (NILs) carrying the Wxa or Wxin allele produced more chalky grain than the R498 parent. A similar result was also observed in the 3611 background. Notably, the effect of the Wx genotype on rice chalkiness was shown to be dependent on environmental conditions, and Wx alleles exhibited different sensitivities to shading treatment. Using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), the Wxa promoter region was successfully edited; down-regulating Wx alleviates chalkiness formation in NILR498-Wxa. This study developed a new strategy for synergistic improvement of eating and appearance qualities in rice, and created a novel Wx allele with great potential in breeding applications.

Nonsynonymous SNPs within C7H15orf39 and NOS2 are associated with boar semen quality.

Spermatogenesis is the developmental process that produces spermatozoa. The aim of this study was to investigate the single nucleotide polymorphisms (SNPs) within C7H15orf39 and NOS2 genes and to determine the correlations between two SNPs and semen quality in Duroc boars (n = 604). The polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method was used for genotyping the selected two nonsynonymous SNPs. The significant correlation was observed between two SNPs (rs80969873: g.58385473 G > A within C7H15orf39; rs325865291: g.44175445 G > A within NOS2) and semen traits in Duroc boars. This study indicates the SNPs in C7H15orf39 and NOS2 may be the potential molecular marker for improving the semen quality traits in Duroc boars.

Sertoli cell survival and barrier function are regulated by miR-181c/d-Pafah1b1 axis during mammalian spermatogenesis.

Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.

BCL2-associated athanogene 6 exon24 contributes to testosterone synthesis and male fertility in mammals.

OBJECTIVES: BCL2-associated athanogene 6 (BAG6) plays critical roles in spermatogenesis by maintaining testicular cell survival. Our previous data showed porcine BAG6 exon24-skipped transcript is highly expressed in immature testes compared with mature testes. The objective of this study is to reveal the functional significance of BAG6 exon24 in mammalian spermatogenesis. MATERIALS AND METHODS: CRISPR/Cas9 system was used to generate Bag6 exon24 knockout mice. Testes and cauda epididymal sperm were collected from mice. TMT proteomics analysis was used to discover the protein differences induced by Bag6 exon24 deletion. Testosterone enanthate was injected into mice to generate a high-testosterone mice model. H&E staining, qRT-PCR, western blotting, vector/siRNA transfection, immunofluorescence, immunoprecipitation, transmission electron microscopy, TUNEL and ELISA were performed to investigate the phenotypes and molecular basis. RESULTS: Bag6 exon24 knockout mice show sub-fertility along with partially impaired blood-testis barrier, increased apoptotic testicular cell rate and abnormal sperm morphology. Endoplasmic reticulum stress occurs in Bag6 exon24-deficient testes and sterol regulatory element-binding transcription factor 2 is activated; as a result, cytochrome P450 family 51 subfamily A member 1 expression is up-regulated, which causes a high serum testosterone level. Additionally, serine/arginine-rich splicing factor 1 down-regulates BAG6 exon24-skipped transcripts in porcine Sertoli cells by binding to 35-51 nt on BAG6 exon24 via its N-terminal RNA-recognition domain. CONCLUSIONS: Our findings reveal the critical roles of BAG6 exon24 in testosterone biosynthesis and male fertility, which provides new insights into the regulation of spermatogenesis and pathogenesis of subfertility in mammals.

Design and establishment of a large-scale controlled ecological life-support system integrated experimental platform.

A Controlled Ecological Life-Support System (CELSS) can meet the demands of food, oxygen, and water for human, as well as providing psychological benefits during deep space exploration by the continuous materials regeneration. Many key techniques of the platform are needed to explore before applying to the extraterrestrial planets. In this study, a large-scale CELSS integrated experimental platform was designed and constructed to meet the basic life-support material demands of six crew members (max). The platform was composed of four kinds of cabins including Crew Cabin (CC), Plant Cabin (PC), Life-Support Cabin (LSC), Resource Recycling Cabin (RRC) and affiliated facilities. Eight cabins were involved in the platform, i.e., CCs I and II, PCs I, II, III and IV, LSC, and RRC. The platform involved 15 subsystems and covered a plant culture area of 206.6 m2 (a max extensible area of 260 m2) and a total volume of 1340 m3. The joint debuggings and the 4-subject 180-day CELSS integration experiment were carried out successfully. The material closures were 55% (on average) for food (70.8% in highly efficient production period), 100% for atmospheric regeneration, 100% for water regeneration, and 87.7% for recycled solid waste in the 4-subject 180-day integration experiment. It verified that the indicators of the platform meet the technical requirements and realize food regeneration, air regeneration and water regeneration through the integration of physico-chemical technique and biological technique for the long-term survivals of six crew members in the closed cabins.

Development of an evaluation indicator system for the rational use of proton pump inhibitors in pediatric intensive care units: An application of Delphi method.

ABSTRACT: Proton pump inhibitors are frequently used to prevent gastrointestinal bleeding in critically ill patients. But there is little information in the instructions about the usages for children. It is important to monitor the appropriate use of proton pump inhibitors, especially in pediatrics. Therefore, we developed an evaluation indicator system for the rational use of proton pump inhibitors in pediatric intensive care units.First, a systematic review was conducted to developed the initial indicators. Then 2 rounds of Delphi surveys were conducted to collecting opinions from a panel of independent experts, and the indicator system was modified to form the final indicators according to the opinions. Finally, the analytic hierarchy procedure was used to determine the weight of each indicator.A total of 6 guidelines and 2 studies met the inclusion and exclusion criteria. Based on literature and discussion among experts, an initial indicator system including 4 first-rank indicators and 12 second-rank indicators was formed. After 2 rounds of Delphi surveys, 2 indicators were added, 5 indicators were deleted, and 1 indicator was revised, so the final indicator system contained a total of 13 indicators including 3 first-rank indicators (drug selection, drug usage and dosage, duration of drug therapy) and 10 second-rank indicators (the proportion of PPIs used in children, children under 1 year old, children who is using glucocorticoids, children with nonsteroidal anti-inflammatory drugs, children with gastroesophageal reflux disease, children with sepsis, children with ventilators in PICU; the strength of PPIs' use, the proportion of omeprazole in children using PPIs during the same period; the average days of PPIs used in children). By analyzing scores, all coefficients met the standard, indicating the indicators were scientific and credible.Through a two-round Delphi survey, 3 first-rank indicators and ten second-rank indicators were developed, which will help drug administrative departments to promote the rational use of PPIs for children in PICUs. What is more, our study can constitute a methodological reference for the development of other indicator systems.

AR regulates porcine immature Sertoli cell growth via binding to RNF4 and miR-124a.

Sertoli cells are the only somatic cells in the seminiferous epithelium which directly contact with germ cells. Sertoli cells exhibit polarized alignment at the basal membrane of seminiferous tubules to maintain the microenvironment for growth and development of germ cells, and therefore play a crucial role in spermatogenesis. Androgens exert their action through androgen receptor (AR) and AR signalling in the testis is essential for maintenance of spermatogonial numbers, blood-testis barrier integrity, completion of meiosis, adhesion of spermatids and spermiation. In the present study, we demonstrated that AR gene could promote the proliferation of immature porcine Sertoli cells (ST cells) and the cell cycle procession, and accelerate the transition from G1 phase into S phase in ST cells. Meanwhile, miR-124a could affect the proliferation and cell cycle procession of ST cells by targeting 3'-UTR of AR gene. Furthermore, AR bound to the RNF4 via AR DNA-binding domain (DBD) and we verified that RNF4 was necessary for AR to regulate the growth of ST cells. Above all, this study suggests that AR regulates ST cell growth via binding to RNF4 and miR-124a, which may help us to further understand the function of AR in spermatogenesis.

Wheat Cultivation and Nutrient Control for the 180-day CELSS Integrated Experiment.

This research aimed to select the well-adapted wheat cultivar and to explore an optimum nutrient control pattern for wheat cultivation in the 180-day integrated experiment of controlled ecological life support system (CELSS). In the experiment, six wheat cultivars from different areas of China were preselected and cultivated in four separate recirculating hydroponic systems (HySy), nutrients in which could be controlled and recycled according the values of pH, electrical conductivity (EC) and dissolved oxygen (DO). Wheat covered an area of 111.3 m2 and had been planted in 17 batches with a 15-day time interval to realize stable regeneration of oxygen, water and food during the 180-day duration in the closed cabin. The results indicated that different cultivars displayed different adaptabilities to the controlled environment. Wt04 had a stronger adaptability with the highest yield (12.82 g DM m-2 d-1) and edible radiation use efficiency (RUE) (0.28 g DM mol-1) whereas Wt06 adapted this environment poorly because of its excessive vegetative growth. For the morphological characters, wheat plants tended to dwarf in the CELSS environment compared with the field. An innovative controlling pattern was established for nutrient supplement. Through the real-time monitoring of pH, EC and DO of the nutrient solution and the periodical detection of the contents of nutrient elements, the nutrient solution could be controlled and recycled continuously without being renewed under a suitable state for wheat plants growth during the 180-day integrated experiment.

Cost-Utility Analysis of four Chelation Regimens for ß-thalassemia Major: a Chinese Perspective.

OBJECTIVE: The Iron chelation is essential to prevent iron overload damage of vital organs, like heart, liver, and endocrine glands, in patients with transfusion-dependent thalassemia. The most common chelation regimens for ß-thalassemia major (ß-TM) patients used in China are a combination therapy of deferoxamine and deferiprone (DFO+DFP), deferoxamine (DFO) monotherapy, deferiprone (DFP) monotherapy and deferasirox (DFX) monotherapy. Such patients use iron chelators their whole lives, resulting in enormous treatment costs. This study analyses the cost-utility of these four regimens from the Chinese healthcare system perspective. METHODS: A Markov decision model was used over a 5-year time horizon and was populated using clinical data from a systematic literature review. We obtained utility data from local and previous research. Costs were estimated using Chinese national sources. RESULTS: From the base-case analysis results, DFP was the most cost-effective chelation regimen, followed by DFO, DFX, and DFO+DFP. DFP had 97.32%, 99.43%, and 58.04% likelihood of being cost-effective versus DFX, DFO+DFP, and DFO, respectively, at a payment threshold of 193,932.00 CNY/QALY (QALY, quality-adjusted life-year). CONCLUSIONS: DFP was the most cost-effective chelation regimen for ß-TM patients, followed by DFO, DFX, and DFO+DFP. Using DFP as the primary treatment regimen may potentially result in cost-savings and QALY gains for the Chinese healthcare system. To increase these benefits, the Chinese government should take measures to lower DFX and DFO drug costs, and Chinese clinicians should choose the cheaper DFX and DFO, increase the utility of DFO+DFP and reduce mortality and morbidity of DFP. Changes in influential parameters easily affect the results of DFX versus DFO+DFP and of DFP versus DFO; clinicians should focus on such parameters and adjust the regimens accordingly.

Mitochondria-Associated Pyruvate Kinase Complexes Regulate Grain Filling in Rice.

Grain filling is a complex agronomic trait that directly determines grain weight and quality in rice (Oryza sativa). Nevertheless, key factors affecting grain filling remain poorly understood. Here, we identified a grain filling gene, OsPK3, encoding a pyruvate kinase (PK). The loss of function of OsPK3 caused reduced PK activity and Suc translocation defects from source to sink in rice, which led to compromised grain filling. OsPK3 was constitutively expressed but had relatively higher expression levels in leaf and developing caryopsis and specific expression signals in tissues involved in Suc transport and unloading, supporting its biological function in regulation of grain filling by affecting Suc translocation. Subcellular localization analysis of OsPK3 revealed its association with mitochondria, and OsPK3 physically interacted and formed heterodimers in vivo with two other PK isozymes, OsPK1 and OsPK4. Both OsPK1 and OsPK4 localized to the mitochondria and cytosol and were recruited to the mitochondria by OsPK3. Despite their high sequence similarity, OsPK1 and OsPK4 had distinct expression patterns. As observed for ospk3, disruption of OsPK1 caused pleiotropic defects, while OsPK4 loss of function led to severely chalky grains without other obvious defects. Collectively, we revealed that two mitochondria-associated pyruvate kinase complexes, OsPK3-OsPK1/OsPK4, are involved in regulation of grain filling by stage-specific fine-tuning of Suc translocation.

Membrane-associated xylanase-like protein OsXYN1 is required for normal cell wall deposition and plant development in rice.

The rice (Oryza sativa) genome encodes 37 putative ß-1,4-xylanase proteins, but none of them has been characterized at the genetic level. In this work, we report the isolation of slim stem (ss) mutants with pleiotropic defects, including dwarfism, leaf tip necrosis, and withered and rolled leaves under strong sunlight. Map-based cloning of the ss1 mutant identified the candidate gene as OsXyn1 (LOC_03g47010), which encodes a xylanase-like protein belonging to the glycoside hydrolase 10 (GH10) family. OsXyn1 was found to be widely expressed, especially in young tissues. Subcellular localization analysis showed that OsXyn1 encodes a membrane-associated protein. Physiological analysis of ss1 and the allelic ss2 mutant revealed that water uptake was partially compromised in these mutants. Consistently, the plant cell wall of the mutants exhibited middle lamella abnormalities or deficiencies. Immunogold assays revealed an unconfined distribution of xylan in the mutant cell walls, which may have contributed to a slower rate of plant cell wall biosynthesis and delayed plant growth. Additionally, water deficiency caused abscisic acid accumulation and triggered drought responses in the mutants. The findings that OsXyn1 is involved in plant cell wall deposition and the regulation of plant growth and development help to shed light on the functions of the rice GH10 family.

Economic Evaluation of Chelation Regimens for ß-Thalassemia Major: a Systematic Review.

BACKGROUND: Deferoxamine (DFO) or Deferiprone (DFP) or Deferasirox (DFX) monotherapy and DFO and DFP combination therapy (DFO+DFP) were four commonly implemented now chelation regimens for the iron overloaded of ß-thalassemia major. This systematic review aims to determine the cost-effectiveness of four chelation regimens and provide evidence for the rational use of chelation regimens for ß-thalassemia major therapy in the clinic. METHODS: A systematic literature search in MEDLINE, EMBASE, the Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, VIP Data, and WanFang Data was conducted in April 2018. In addition, a manual search was performed. Two researchers, working independently, selected the papers, extracted the data, and assessed the methodological quality of the included documents. Each included paper was evaluated using a checklist developed by Drummond et al. RESULTS: The number of records was initially 968, and eight papers met the final eligibility criteria. All the included eight papers were cost-utility analyses, and their methodological quality was fair. In these eight papers, nineteen studies were present. Nine studies of DFX versus DFO had contradictory results. Out of the nineteen studies, three studies of DFX versus DFP established that using DFP was cost-effective. Three studies of DFP versus DFO proved that using DFP was cost-effective. One survey of DFO+DFP versus DFO found that using DFO was cost-effective. One study of DFO+DFP versus DFP found that using DFP was cost-effective. Moreover, there were two studies of DFO+DFP versus DFX, but we cannot be sure which one of two chelation regimens was cost-effective. CONCLUSION: In brief, DFP is cost-effective, followed by DFO or DFX, when an iron chelator is to be used alone for ß-thalassemia iron overload treatment. All studies that compared DFO+DFP with DFO (or DFP) monotherapy established that the DFO+DFP was not cost-effective. Existing studies about DFO+DFP versus DFX could not prove which one of two chelation regimens was cost-effective. However, due to the low number of DFO+DFP versus DFO (or DFP or DFX) monotherapy studies, more extensive, high-quality research is required for further analysis and confirmation of our findings. Moreover, the cost-effectiveness is not an absolute issue when in different countries (regions) the results are opposite for other countries (regions). As a result, the local/national context had a substantial influence on the results of the pharmacoeconomic evaluation.

H2AFZ, RNF4 and NR4A1 loci are associated with boar semen quality by population association studies.

Spermatogenesis is a complex process regulated by many genes. In this study, H2AFZ, RNF4 and NR4A1 genes were selected as candidate genes for boar semen quality traits based on their functions during spermatogenesis, and the associations of three loci (H2AFZ c.192 + 210-192 + 213delCGAT, RNF4 c.374 + 358 T > C and NR4A1 c.956 + 796 A > G) with sperm quality traits were analyzed in Duroc (n = 185), Large White (n = 87) and Landrace (n = 49) pig populations. The results showed H2AFZ c.192 + 210-192 + 213delCGAT AA boars produced 1.52% lower abnormal sperm rate (ASR) than AB boars in Landrace pigs (p < 0.05); RNF4 c.374 + 358 TC boars produced 0.31 × 108/ml higher sperm concentration (SCON) than CC boars (p < 0.05) in Large White pigs; NR4A1 c.956 + 796 A > G was associated with ASR in Duroc and Large White pigs and was associated with sperm motility (MOT) in Large White and Landrace pigs. This study indicated the H2AFZ, RNF4 and NR4A1 loci were the potential molecular markers for improving the semen quality traits in boars.

The drug use to treat community-acquired pneumonia in children: A cross-sectional study in China.

To evaluate the rationality of drug use to treat community-acquired pneumonia (CAP) in children of a Chinese hospital using a set of developed indicators.We performed a retrospective cross-sectional study in West China Second University Hospital. Hospitalized children (0-18 years old) diagnosed with CAP from October 2015 to January 2016 were included. A set of developed indicators for assessing rational drug use (RDU) to treat CAP in children were used to evaluate the rationality of drug use. The data of the indicators were compared with the recommendations of the available guidelines, analyzing the situation of drug use in the children diagnosed with CAP.Eight hundred ninety-four children were included, 99.4% of them received antibiotics and 87.4% received more than 1 antibiotic. Antibiotics were administered intravenously in 880 (99.0%) children. About 20 (2.2%) children received antiviral agents and 19 (2.1%) children received antiviral drugs combined with antibiotics. About 208 (23.3%) children received traditional Chinese medicines and the injection of traditional Chinese medicines was given in 20 (2.2%) children.This study illustrated that drug use was partly not consistent with the recommendations of current guidelines, especially antibiotics. The drug use of CAP in children needs to pay more attention to.

Analysis of influencing factors of boar claw lesion and lameness.

This study aimed to investigate the factors affecting boar claw lesions and lameness. A total of 1299 boars were examined for claw lesions and lameness, including 788 boars reared in individual pens with solid concreted floor (IPS) and 511 boars raised in individual stalls with slatted floor (ISS). Flooring type showed significant impacts on all claw lesion types (P < 0.01). Except for swelling ankle, boar age had significant effects on all other claw lesion types (P < 0.01). In addition, only heel overgrowth and erosion, cracked wall horizontal, heel-sole crack, dew claws, and toes were significantly related to boar breeds (P < 0.05). Furthermore, IPS lame boars had higher prevalence of lameness in the hind limb (P < 0.05), whereas in ISS lame boars, there were no significant differences in prevalence of lameness between the fore and hind limbs (P > 0.05). Boar lameness was moderately correlated with swelling ankle (Φ = 0.5571). In conclusion, claw lesions can be influenced by flooring type, boar age and breed, and could serve as a predictor for boar lameness.

miR-638 Inhibits immature Sertoli cell growth by indirectly inactivating PI3K/AKT pathway via SPAG1 gene.

Numerous studies have demonstrated that microRNAs (miRNAs) play important roles in cell growth, apoptosis and spermatogenesis. Our previous study showed that miR-638 was differentially expressed in sexually immature and mature testes of Large White boars. Here we reported that sperm-associated antigen 1 (SPAG1) was a direct target gene of miR-638. Moreover, miR-638 inhibited cell proliferation and cell cycle, and promoted apoptosis of porcine immature Sertoli cells. Key genes including phosphorylated phosphatidylinositide 3-kinases (p-PI3K) and phosphorylated serine/ threonine kinase (p-AKT) in PI3K/AKT pathway as well as cell cycle factors including c-MYC, cyclin-D1 (CCND1), cyclin-E1 (CCNE1) and cyclin-dependent kinase 4 (CDK4) were all significantly down-regulated after overexpression of miR-638 or RNAi of SPAG1. Notably, mRNA levels of SRY-related HMG-box 2 (SOX2) and POU domain, class 5, transcription factor 1 (POU5F1) essential for spermatogonia proliferation were significantly suppressed in SPAG1 siRNA- transfected ST cells. This study suggests that miR-638 regulates immature Sertoli cell growth and apoptosis by targeting SPAG1 gene which can indirectly inactivate PI3K/AKT pathway, and plays roles in pig spermatogenesis.