Arbuscular mycorrhizal fungi inhibit necrotrophic, but not biotrophic, aboveground plant pathogens: a meta-analysis and experimental study.

Microbial mutualists can profoundly modify host species ecology and evolution, by extension altering interactions with other microbial species, including pathogens. Arbuscular mycorrhizal fungi (AMF) may moderate infections by pathogens, but the direction and strength of these effects can be idiosyncratic. To assess how the introduction of AMF impacts the incidence and severity of aboveground plant diseases (i.e. 'disease impact'), we conducted a meta-analysis of 130 comparisons derived from 69 published studies. To elucidate the potential mechanisms underlying the influence of AMF on pathogens, we conducted three glasshouse experiments involving six non-woody plant species, yielded crucial data on leaf nutrient composition, plant defense compounds, and transcriptomes. Our meta-analysis revealed that the inoculation of AMF lead to a reduction in disease impact. More precisely, AMF inoculation was associated with a decrease in necrotrophic diseases, while no significant impact on biotrophic diseases. Chemical and transcriptome analyses suggested that these effects may be driven by AMF regulation of jasmonic acid and salicylic acid signaling pathways in glasshouse experiments. However, changes in plant nutritional status and secondary chemicals may also regulate disease impact. These results emphasize the importance of incorporating pathogen life history when predicting how microbial mutualisms affect disease impact.

Genetic association and functional validation of ZFP36L2 in non-syndromic orofacial cleft subtypes.

BACKGROUND: Non-syndromic orofacial cleft (NSOC) is one of the most common craniofacial malformations with complex etiology. This study aimed to explore the role of specific SNPs in ZFP36L2 and its functional relevance in zebrafish models. METHODS: We analyzed genetic data of the Chinese Han population from two previous GWAS, comprising of 2512 cases and 2255 controls. Based on the Hardy-Weinberg Equilibrium (HWE) and minor allele frequency (MAF), SNPs in the ZFP36L2 were selected for association analysis. In addition, zebrafish models were used to clarify the in-situ expression pattern of zfp36l2 and the impact of its Morpholino-induced knockdown. RESULTS: Via association analysis, rs7933 in ZFP36L2 was significantly associated with various non-syndromic cleft lip-only subtypes, potentially conferring a protective effect. Zebrafish embryos showed elevated expression of zfp36l2 in the craniofacial region during critical stages of oral cavity formation. Furthermore, Morpholino-induced knockdown of zfp36l2 led to craniofacial abnormalities, including cleft lip, which was partially rescued by the addition of zfp36l2 mRNA. CONCLUSION: Our findings highlight the significance of ZFP36L2 in the etiology of NSOC, supported by both human genetic association data and functional studies in zebrafish. These results pave the way for further exploration of targeted interventions for craniofacial malformations.

[Mechanisms of the Effect of Maternal Age-Related Oocyte Aging on Fertility: Transcriptomic Sequencing Analysis of a Zebrafish Model]. / æ¯ä½“å¹´é¾„ç›¸å ³çš„åµæ¯ç»†èƒžè€åŒ–å¯¹ç”Ÿè‚²åŠ›çš„å½±å“æœºåˆ¶ï¼šæ–‘é©¬é±¼æ¨¡åž‹çš„è½¬å½•ç»„å­¦æµ‹åºåˆ†æž.

Objective: Female fertility gradually decreases with the increase in women's age. The underlying reasons include the decline in the quantity and quality of oocytes. Oocyte aging is an important manifestation of the decline in oocyte quality, including in vivo oocyte aging before ovulation and in vitro oocyte aging after ovulation. Currently, few studies have been done to examine oocyte aging, and the relevant molecular mechanisms are not fully understood. Therefore, we used zebrafish as a model to investigate oocyte aging. Three different age ranges of female zebrafish were selected to mate with male zebrafish of the best breeding age. In this way, we studied the effects of maternal age-related oocyte aging on fertility and investigated the potential molecular mechanisms behind maternal age-related fertility decline. Methods: Eight female zebrafish aged between 158 and 195 d were randomly selected for the 6-month age group (180±12) d, 8 female zebrafish aged between 330 and 395 d were randomly selected for the 12-month age group (360±22) d, and 8 female zebrafish aged between 502 and 583 d were randomly selected for the 18-month age group (540±26) d. Male zebrafish of (180±29) d were randomly selected from zebrafish aged between 158 and 195 d and mated with female zebrafish in each group. Each mating experiment included 1 female zebrafish and 1 male zebrafish. Zebrafish embryos produced by the mating experiments were collected and counted. The embryos at 4 hours post-fertilization were observed under the microscope, the total number of embryos and the number of unfertilized embryos were counted, and the fertilization rate was calculated accordingly. The numbers of malformed embryos and dead embryos were counted 24 hours after fertilization, and the rates of embryo malformation and mortality were calculated accordingly. The primary outcome measure was the embryo fertilization rate, and the secondary outcome measures were the number of embryos per spawn (the total number of embryos laid within 1.5 hours after the beginning of mating and reproduction of the zebrafish), embryo mortality, and embryo malformation rate. The outcome measures of each group were compared. The blastocyst embryos of female zebrafish from each group born after mating with male zebrafish in their best breeding period were collected for transcriptomics analysis. Fresh oocytes of female zebrafish in each group were collected for transcriptomics analysis to explore the potential molecular mechanisms of maternal age-related fertility decline. Results: Compared with that of the 6-month group (94.9%±3.6%), the embryo fertilization rate of the 12-month group (92.3%±4.2%) showed no significant difference, but that of the 18-month group (86.8%±5.5%) decreased significantly (P<0.01). In addition, the fertilization rate in the 18-month group was significantly lower than that in the 12-month group (P<0.05). Compared with that of the 6-month group, the embryo mortality of the female zebrafish in the 12-month group and that in the 18-month group were significantly higher than that in the 6-month group (P<0.000 1, P<0.001). There was no significant difference in the number of embryos per spawn or in the embryo malformation rate among the three groups. The results of the transcriptomics analysis of blastocyst embryos showed that some genes, including dusp5, bdnf, ppip5k2, dgkg, aldh3a2a, acsl1a, hal, mao, etc, were differentially expressed in the 12-month group or the 18-month group compared with their expression levels in the 6-month group. According to the KEGG enrichment analysis, these differentially expressed genes (DEGs) were significantly enriched in the MAPK signaling pathway, the phosphatidylinositol signaling system, and the fatty acid degradation and histidine metabolism pathway (P<0.05). The analysis of the expression trends of the genes expressed differentially among the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that the gene expression trends of fancc, fancg, fancb, and telo2, which were involved in Fanconi anemia pathway, were statistically significant (P<0.05). In the results of oocyte transcriptomics analysis, the genes that were differentially expressed in the 12-month group or the 18-month group compared with the 6-month group were mainly enriched in cell adhesion molecules and the protein digestion and absorption pathway (P<0.05). The results of the trends of gene expression in the zebrafish oocytes of the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that three kinds of gene expression trends of declining fertility with growing maternal age had significant differences (P<0.05). Further analysis of the three significantly differential expression trends showed 51 DEGs related to mitochondria and 5 DEGs related to telomere maintenance and DNA repair, including tomm40, mpc2, nbn, tti1, etc. Conclusion: With the increase in the maternal age of the zebrafish, the embryo fertilization rate decreased significantly and the embryo mortality increased significantly. In addition, with the increase in the maternal age of the zebrafish, the expression of mitochondria and telomere-related genes, such as tomm40, mpc2, nbn, and tti1, in female zebrafish oocytes decreased gradually. Maternal age may be a factor contributing to the decrease in oocyte fertilization ability and the increase in early embryo mortality. Maternal age-related oocyte aging affects the fertility and embryo development of the offspring.

Identification of POLR3B biallelic mutations-associated hypomyelinating leukodystrophy-8 in two siblings.

POLR3B gene encodes the 2nd largest catalytic subunit and affects the function of RNA polymerase III enzymes in transcription. Bi-allelic variants in POLR3B pathogenically cause hypomyelinating leukodystrophy-8 (HLD8). Herein, we recruited a family with two patients, who presented clinically with cerebellar atrophy, intellectual disability, hypogonadotropic hypogonadism, and visual problems. We identified the two affected siblings carrying the compound heterozygous variations (c.165_167del; c.1615G>T) in POLR3B by trio-whole-exome sequencing (trio-WES). The qPCR and western blot showed that both transcriptional and translational levels of the mutation (c.165_167del, p.I55_K56delinsM) were sharply attenuated. Following that, a thorough functional examination of a zebrafish line disrupted for human POLR3B validated the pathogenic effects of the two mutations. Our research broadens the spectrum of HLD8-related pathogenic POLR3B mutations and provides new molecular and animal evidence.

Plant community-mediated effects of grazing on plant diseases.

Grazing is one of the most important management practices for grasslands. To date, most studies on how grazing affects plant diseases have focused on a single plant species, ignoring plant community characteristics and phylogeny. We used data from a 6-year yak grazing experiment (0, 1, 2, and 3 yak(s) ha - 1 treatment) in an alpine meadow ecosystem of Qinghai-Tibetan Plateau, from which we tested grazing effects on foliar fungal diseases at both population and community levels. By measuring plant community variables (including richness, evenness, phylogenetic diversity, and composition) and disease severity, we evaluated the relative importance of plant community-mediated effects of yak grazing on community pathogen load with a multi-model inference approach. We found significant differences in pathogen load among different grazing treatments; we recorded the highest and lowest pathogen loads in the 1 yak ha - 1 treatment and in the 3 yaks ha - 1 treatment, respectively. Pielou's evenness index and community proneness (i.e., an estimate of the capacity of plant communities to support diseases) best explained variation in pathogen load, indicating that plant community-mediated effects (through evenness and proneness) of yak grazing determined pathogen load. Our study provides empirical evidence that grazing influences foliar fungal disease prevalence through plant community evenness and composition, which demonstrates the necessity of incorporating host plant community characteristics into disease load prediction frameworks.

Compound heterozygous variations in IARS1 cause recurrent liver failure and growth retardation in a Chinese patient: a case report.

BACKGROUND: Aminoacyl-tRNA synthetases (ARSs) are enzymes responsible for attaching amino acids to tRNA, which enables protein synthesis. Mutations in isoleucyl-tRNA synthetase (IARS1) have recently been reported to be a genetic cause for growth retardation, intellectual disability, muscular hypotonia, and infantile hepatopathy (GRIDHH). CASE PRESENTATION: In this study, we reported an additional case of compound heterozygous missense variations c.701 T > C (p.L234P) and c.1555C > T (p.R519C) in IARS1, which were identified using medical exome sequencing; c.701 T > C (p.L234P) was a novel variant, and c.1555C > T (p.R519C) was found in GnomAD. Unlike other reported patients, this individual presented prominently with recurrent liver failure, which led to her death at an early age of 19 months. She also had significant growth retardation, muscular hypotonia, chubby and flabby face, recurrent loose stools, and abnormal brain computed tomography (CT), while zinc deficiency and hearing loss were not present. Studies in zebrafish embryo modeling recapitulated some of the key phenotypic traits in embryo development, neurodevelopment, liver development, and myogenesis, demonstrating that these variations caused a loss of gene function in IARS1. CONCLUSIONS: We have found a novel mutation point c.701 T > C (p.L234P) in IARS1. Compound heterozygous mutations of c.701 T > C (p.L234P) and c.1555C > T (p.R519C) in IARS1 are pathogenic, which can cause GRIDHH in child.

A novel de novo missense mutation in EFTUD2 identified by whole-exome sequencing in mandibulofacial dysostosis with microcephaly.

BACKGROUND: Mandibulofacial dysostosis with microcephaly (MFDM) is a rare multiple malformation syndrome characterized by malar and mandibular hypoplasia and congenital- or postnatal-onset microcephaly induced by haploinsufficiency of (elongation factor Tu GTP-binding domain-containing 2) EFTUD2. METHODS: We report the case of a 16-month-old boy with MFDM symptoms, including malar and mandibular hypoplasia, microcephaly, micrognathia, midline cleft palate, microtia, auditory canal atresia, severe sensorineural hearing loss, and developmental delay. Whole-exome sequencing (WES) analysis of the patient's family was performed to identify the genetic etiology responsible for this phenotype. RESULTS: We identified a novel de novo missense mutation (c.671G>T, p.Gly224Val) in the EFTUD2. According to the American College of Medical Genetics and Genomics (ACMG) 2015 guidelines, the c.671G>T mutation was classified as likely pathogenic (PS2, PM1, PM2, and PP3). Based on our findings, prenatal diagnosis was performed on the second baby of the proband's parents to exclude the mutation and it was confirmed that the baby did not have the MFDM phenotype after 14 months of follow-up. Furthermore, the zebrafish model confirmed that the EFTUD2 c.671G>T mutation caused a loss of gene function in EFTUD2, and the pathogenicity of the EFTUD2 c.671G>T mutation was classified as pathogenic (PS2, PS3, PM1, and PM2). CONCLUSION: Our results indicate that WES is a useful tool for identifying potentially pathogenic mutations, particularly in rare disorders, and is advantageous for genetic counseling and subsequent prenatal diagnosis. Moreover, the importance of functional assays cannot be underestimated, which could further confirm the pathogenicity of the genetic variants.

Organic matter removal performance, pathway and microbial community succession during the construction of high-ammonia anaerobic biosystems treating anaerobic digestate food waste effluent.

This study aimed to establish anaerobic biosystems which could tolerate high ammonia, and investigate the microbial community structure in these reactors. High-ammonia anaerobic biosystems that could tolerate 3600 mg L-1 total ammonia nitrogen (TAN) and 1000 mg L-1 free ammonia nitrogen (FAN) were successfully established. The removal efficiencies of COD and total volatile fatty acids (TVFAs) in R1 with dewatered sludge as inoculum were 68.8% and 69.2%, respectively. The maximum methane production rate reached 71.7 ± 1.0 mL CH4 L-1 d-1 at a TAN concentration of 3600 mg L-1. The three-dimension excitation-emission matrix analysis indicated that both easily degradable organics and refractory organics were removed from ADFE in R1 and R2. Functional microorganisms which could bear high ammonia were gradually enriched as TAN stress was elevated. Lysinibacillus, Coprothermobacter and Sporosarcina dominated the final bacterial community. Archaeal community transformed to hydrogenotrophic methanogen. The synergy of Coprothermobacter and Methanothermobacter undertook the organic matter degradation, and was enhanced by increasing TAN stress. This study offers new insights into anaerobic bioremediation of ammonia-rich wastewater.

Contrasting effects of mammal grazing on foliar fungal diseases: patterns and potential mechanisms.

Plant pathogens and their hosts often coexist with mammal grazers. However, the direction and strength of grazing effects on foliar fungal diseases can be idiosyncratic, varying among host plant species and pathogen types. We combined a 6 yr yak-grazing experiment, a clipping experiment simulating different mammal consumption patterns (leaf damage vs whole-leaf removal), and a meta-analysis of 63 comparisons to evaluate how grazing impacts foliar fungal diseases across plant growth types (grass vs forb) and pathogen life histories (biotroph vs necrotroph). In the yak-grazing experiment, grazing had no significant effect on disease severity, and grasses experienced a higher disease severity than forbs; there was a significant interaction between pathogen type and grazing. In both the yak-grazing experiment and meta-analysis, grazing decreased biotrophic pathogens (mainly rusts and powdery mildew), but did not affect necrotrophic pathogens (mainly leaf spots). The clipping experiment suggested that grazers might promote infection by necrotrophic pathogens by producing wounds on leaves, but inhibit biotrophic pathogens via leaf removal. In conclusion, our three-part approach revealed that intrinsic properties of both plants and pathogens shape patterns of disease in natural ecosystems, greatly improving our ability to predict disease severity under mammal grazing.

Emerging Group-VI Elemental 2D Materials: Preparations, Properties, and Device Applications.

Due to the ultrathin thickness and dangling-bond-free surface, 2D materials have been regarded as promising candidates for future nanoelectronics. In recent years, group-VI elemental 2D materials have been rediscovered and found superior in electrical properties (e.g., high carrier mobility, high photoconductivity, and thermoelectric response). The outstanding semiconducting properties of group-VI elemental 2D materials enable device applications including high-performance field-effect transistors and optoelectronic devices. The excellent environmental stability also facilitates fundamental studies and practical applications of group-VI elemental 2D materials. This Review first focuses on the crystal structures of group-VI elemental 2D materials. Afterward, preparation methods for nanostructures of group-VI materials are introduced with comprehensive studies. A brief Review of the electronic structures is then presented with an understanding of the electrical properties. This Review also contains the device applications of group-VI elemental 2D materials, emphasizing transistors, photodetectors, and other appealing applications. Finally, this Review provides an outlook for the development of group-VI elemental 2D materials, highlighting the challenges and opportunities in fundamental studies and technological applications.

Two-Dimensional Antiferroelectricity in Nanostripe-Ordered In_{2}Se_{3}.

Two-dimensional (2D) layered materials have been an exciting frontier for exploring emerging physics at reduced dimensionality, with a variety of exotic properties demonstrated at 2D limit. Here, we report the first experimental discovery of in-plane antiferroelectricity in a 2D material ß^{'}-In_{2}Se_{3}, using optical and electron microscopy consolidated by first-principles calculations. Different from conventional 3D antiferroelectricity, antiferroelectricity in ß^{'}-In_{2}Se_{3} is confined within the 2D layer and generates the unusual nanostripe ordering: the individual nanostripes exhibit local ferroelectric polarization, whereas the neighboring nanostripes are antipolar with zero net polarization. Such a unique superstructure is underpinned by the intriguing competition between 2D ferroelectric and antiferroelectric ordering in ß^{'}-In_{2}Se_{3}, which can be preserved down to single-layer thickness as predicted by calculation. Besides demonstrating 2D antiferroelectricity, our finding further resolves the true nature of the ß^{'}-In_{2}Se_{3} superstructure that has been under debate for over four decades.

Novel nesprin-1 mutations associated with dilated cardiomyopathy cause nuclear envelope disruption and defects in myogenesis.

Nesprins-1 and -2 are highly expressed in skeletal and cardiac muscle and together with SUN (Sad1p/UNC84)-domain containing proteins and lamin A/C form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) bridging complex at the nuclear envelope (NE). Mutations in nesprin-1/2 have previously been found in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) as well as dilated cardiomyopathy (DCM). In this study, three novel rare variants (R8272Q, S8381C and N8406K) in the C-terminus of the SYNE1 gene (nesprin-1) were identified in seven DCM patients by mutation screening. Expression of these mutants caused nuclear morphology defects and reduced lamin A/C and SUN2 staining at the NE. GST pull-down indicated that nesprin-1/lamin/SUN interactions were disrupted. Nesprin-1 mutations were also associated with augmented activation of the ERK pathway in vitro and in hearts in vivo. During C2C12 muscle cell differentiation, nesprin-1 levels are increased concomitantly with kinesin light chain (KLC-1/2) and immunoprecipitation and GST pull-down showed that these proteins interacted via a recently identified LEWD domain in the C-terminus of nesprin-1. Expression of nesprin-1 mutants in C2C12 cells caused defects in myoblast differentiation and fusion associated with dysregulation of myogenic transcription factors and disruption of the nesprin-1 and KLC-1/2 interaction at the outer nuclear membrane. Expression of nesprin-1α2 WT and mutants in zebrafish embryos caused heart developmental defects that varied in severity. These findings support a role for nesprin-1 in myogenesis and muscle disease, and uncover a novel mechanism whereby disruption of the LINC complex may contribute to the pathogenesis of DCM.

CFTR is required for the migration of primordial germ cells during zebrafish early embryogenesis.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene affect fertility in both sexes. However, the involvement of CFTR in regulating germ cell development remains largely unknown. Here, we used zebrafish model to investigate the role of CFTR in primordial germ cells (PGCs) development. We generated a cftr frameshift mutant zebrafish line using CRISPR/Cas9 technique and investigated the migration of PGCs during early embryo development. Our results showed that loss of Cftr impairs the migration of PGCs from dome stages onward. The migration of PGCs was also perturbed by treatment of CFTRinh-172, a gating-specific CFTR channel inhibitor. Moreover, defected PGCs migration in cftr mutant embryos can be partially rescued by injection of WT but not other channel-defective mutant cftr mRNAs. Finally, we observed the elevation of cxcr4b, cxcl12a, rgs14a and ca15b, key factors involved in zebrafish PGCs migration, in cftr-mutant zebrafish embryos. Taken together, the present study revealed an important role of CFTR acting as an ion channel in regulating PGCs migration during early embryogenesis. Defect of which may impair germ cell development through elevation of key factors involved in cell motility and response to chemotactic gradient in PGCs.

Phase and Facet Control of Molybdenum Carbide Nanosheet Observed by In Situ TEM.

Transition metal carbides are of great potential for electrochemical applications. The phase and facet of molybdenum carbides greatly affect the electrochemical performance. Carburization of MoO3 inside a transmission electron microscope to monitor the growth process of molybdenum carbides is performed. Carbon sources with different activities are used and the controllable growth of molybdenum carbides is investigated. The results show that the relatively inert amorphous carbon film produces Mo2 C, where the interstitial sites formed by hexagonal closed packing molybdenum atoms are partially occupied by carbon atoms. In contrast, the carbon decomposed from the sucrose has a high portion of sp3 hybridized and crosslinked carbon atoms with high reactivity, leading to the formation of MoC with full occupation of interstitial sites by carbon atoms. In addition, the MoC growth experiences a (111) to (100) facets change with the increase of temperature. The (111) facet formed at low temperature has Mo-terminated or C-terminated surface with higher surface energy and higher reactivity, while the (100) facet with 1:1 C/Mo ratio on the surface exhibits enhanced stability. The phase and facet control by carbon source and temperature allow us to tune the crystal structures and surface atoms as well as their electrochemical properties.

Infrared light gated MoS2 field effect transistor.

Molybdenum disulfide (MoS2) as a promising 2D material has attracted extensive attentions due to its unique physical, optical and electrical properties. In this work, we demonstrate an infrared (IR) light gated MoS2 transistor through a device composed of MoS2 monolayer and a ferroelectric single crystal Pb(Mg(1/3)Nb(2/3))O3-PbTiO3 (PMN-PT). With a monolayer MoS2 onto the top surface of (111) PMN-PT crystal, the drain current of MoS2 channel can be modulated with infrared illumination and this modulation process is reversible. Thus, the transistor can work as a new kind of IR photodetector with a high IR responsivity of 114%/Wcm⁻². The IR response of MoS2 transistor is attributed to the polarization change of PMN-PT single crystal induced by the pyroelectric effect which results in a field effect. Our result promises the application of MoS2 2D material in infrared optoelectronic devices. Combining with the intrinsic photocurrent feature of MoS2 in the visible range, the MoS2 on ferroelectric single crystal may be sensitive to a broadband wavelength of light.

Altered N6-methyladenosine methylation level in spermatozoa messenger RNA of the male partners is related to unexplained recurrent pregnancy loss.

BACKGROUND: Understanding the pathogenesis of unexplained recurrent pregnancy loss is paramount for advancing effective treatments. Various biological processes, including spermatogenesis and embryo development, are tightly regulated by N6-methyladenosine modifications. However, few studies have focused on the impact of sperm N6-methyladenosine modifications on embryonic development. Therefore, we aimed to study altered N6-methyladenosine-mediated messenger RNA methylation modifications in the spermatozoa of male partners from couples experiencing unexplained recurrent pregnancy loss, to identify potential diagnostic markers and explore their potential molecular mechanisms in pregnancy loss and embryogenesis. METHODS: Methylated RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing were conducted on the spermatozoa of men from couples in the 'unexplained recurrent pregnancy loss' group (n = 6), and the fertility control group (n = 6). To identify the role of the detected key genes, zebrafish model embryos were studied, and multi-omics (transcriptomics, proteomics, and metabolomics) analyses helped to explore the molecular mechanism of abnormal embryogenesis. FINDINGS: Comparing unexplained recurrent pregnancy loss with the fertility control group, 217 N6-methyladenosine peaks were significantly upregulated, and 40 were downregulated in the spermatozoa. The combined analyses of spermatozoa-methylated RNA immunoprecipitation sequencing and RNA sequencing indicated that N6-methyladenosine methylation and the expression of SEMA5A, MT-ATP6, ZNF662, and KDM4C were significantly different. In zebrafish embryos, the altered expression of the four genes increased embryonic mortality and malformations by disturbing several key signaling pathways and zygotic genome activation. INTERPRETATION: This study highlights the paternal epigenome, which could be one of the reasons for faulty embryogenesis leading to pregnancy loss. The N6-methyladenosine modification, the most prevalent RNA modification, contributes to the exploration and understanding of the paternal epigenome in the maintenance of pregnancy and fetal growth and development. The four genes identified in this study may serve as potential diagnostic markers and elucidate novel molecular mechanisms of embryogenesis.

RCAN family member 3 deficiency contributes to noncompaction of the ventricular myocardium.

Noncompaction of the ventricular myocardium (NVM), the third most diagnosed cardiomyopathy, is characterized by prominent trabeculae and intratrabecular recesses. However, the genetic etiology of 40%-60% of NVM cases remains unknown. Here, we identify two infants with NVM, in a nonconsanguineous family, with a typical clinical presentation of persistent bradycardia since the prenatal period. A homozygous missense variant (R223L) of RCAN family member 3 (RCAN3) is detected in both infants using whole-exome sequencing. In the zebrafish model, marked cardiac dysfunction is detected in rcan3 deficiency (MO-rcan3ATG-injected) and rcan-/- embryos. Developmental dysplasia of both endocardial and myocardial layers is also detected in rcan3-deficient embryos. RCAN3 R223L variant mRNAs can not rescue heart defects caused by rcan3 knockdown or knockout; however, hRCAN3 mRNAs rescue these phenotypes. RNA-seq experiments show that several genes involved in cardiomyopathies are significantly regulated through multiple signaling pathways in the rcan3-knockdown zebrafish model. In human cardiomyocytes, RCAN3 deficiency results in reduced proliferation and increased apoptosis, together with an abnormal mitochondrial ultrastructure. Thus, we suggest that RCAN3 is a susceptibility gene for cardiomyopathies, especially NVM and that the R223L mutation is a potential loss-of-function variant.

Effects and mechanisms of polycyclic aromatic hydrocarbons in inflammatory skin diseases.

Polycyclic aromatic hydrocarbons (PAHs) are hydrocarbons characterized by the presence of multiple benzene rings. They are ubiquitously found in the natural environment, especially in environmental pollutants, including atmospheric particulate matter, cigarette smoke, barbecue smoke, among others. PAHs can influence human health through several mechanisms, including the aryl hydrocarbon receptor (AhR) pathway, oxidative stress pathway, and epigenetic pathway. In recent years, the impact of PAHs on inflammatory skin diseases has garnered significant attention, yet many of their underlying mechanisms remain poorly understood. We conducted a comprehensive review of articles focusing on the link between PAHs and several inflammatory skin diseases, including psoriasis, atopic dermatitis, lupus erythematosus, and acne. This review summarizes the effects and mechanisms of PAHs in these diseases and discusses the prospects and potential therapeutic implications of PAHs for inflammatory skin diseases.

Embryotoxicity evaluation of Gentamicin, an aminoglycoside antibiotic added to human embryo culture medium, using the zebrafish (Danio rerio) model.

Infertility gives rise to a lot of social and psychological problems. At present, assisted reproductive technology (ART) is an important way to solve infertility. However, the live birth rate of in vitro fertilization and embryo transfer (IVF-ET) is less than 50 %. Medium is essential for the culture of embryos in vitro. Therefore, we want to explore whether the composition of the culture medium affects the survival rate of embryos. Gentamicin (GM) is an aminoglycoside antibiotic that is used to treat various bacterial infections. It is widely used in IVF medium, but it is not known whether it has a toxicity effect on embryonic development. Here, we used zebrafish embryos to investigate the embryotoxicity of GM which is an ingredient in culture medium. Our results found that there was no significant effect on the zebrafish embryo development, including survival rate, malformation rate and developmental time course, while zebrafish embryos were treated with GM at the culture medium concentration (10 mg/L, 17.8 µM) compared with the control group. To research the potential embryotoxicity of GM, we treated zebrafish embryos with GM with high concentration (range from 17.8 µM to 3000 µM). The results showed that the lethal concentration of 50 % (LC50) at 48-h post-fertilization (hpf) value of zebrafish embryos for GM was 1150 µM; the survival rate and malformation rate of zebrafish embryos were significantly changed in a dose-dependent manner. Furthermore, transcriptomics, metabolomics and epigenomics (m6A-MeRIP-seq) were used to investigate the molecular mechanism of embryotoxicity, and results showed cell cycle, dorso-ventral axis formation and collecting duct acid secretion pathway were altered significantly in treated embryos. In conclusion, there are no adverse effects on embryonic development with the working concentration of GM in human culture medium, suggesting that GM is safe for embryo culture at working concentration.