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.

[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.

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.

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.

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.

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.

Novel bi-allelic variants of CHMP1A contribute to pontocerebellar hypoplasia type 8: additional clinical and genetic evidence.

Pontocerebellar hypoplasia type 8(PCH8) is a rare neurodegenerative disorder, reportedly caused by pathogenic variants of the CHMP1A in autosomal recessive inheritance, and CHMP1A variants have also been implicated in other diseases, and yet none of the prenatal fetal features were reported in PCH8. In this study, we investigated the phenotype and genotype in a human subject with global developmental delay, including clinical data from the prenatal stage through early childhood. Prenatally, the mother had polyhydramnios, and the bilateral ventricles of the fetus were slightly widened. Postnatally, the infant was observed to have severely delayed psychomotor development and was incapable of visual tracking before 2 years old and could not fix on small objects. The young child had hypotonia, increased knee tendon reflex, as well as skeletal malformations, and dental crowding; she also had severe and recurrent pulmonary infections. Magnetic resonance imaging of the brain revealed a severe reduction of the cerebellum (vermis and hemispheres) and a thin corpus callosum. Through whole exome sequencing and whole genomics sequencing, we identified two novel compound heterozygous variations in CHMP1A [c.53 T > C(p.Leu18Pro)(NM_002768.5) and exon 1 deletion region (NC_000016.10:g.89656392_89674382del)]. cDNA analysis showed that the exon1 deletion region led to the impaired expression, and functional verification with zebrafish embryos using base edition indicated variant c.53 T > C (p.Leu18Pro), causing dysplasia of the cerebellum and pons. These results provide further evidence that CHMP1A variants in a recessive inheritance pattern contribute to the clinical characteristics of PCH8 and further expand our knowledge of the phenotype and genotype spectrum of PCH8.

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.

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.

Spatial scale-dependent dilution effects of biodiversity on plant diseases in grasslands.

The rapid biodiversity losses of the Anthropocene have motivated ecologists to understand how biodiversity affects infectious diseases. Spatial scale is thought to moderate negative biodiversity-disease relationships (i.e., dilution effects) in zoonotic diseases, whereas evidence from plant communities for an effect of scale remains limited, especially at local scales where the mechanisms (e.g., encounter reduction) underlying dilution effects actually work. Here, we tested how spatial scale affects the direction and magnitude of biodiversity-disease relationships. We utilized a 10-year-old nitrogen addition experiment in a Tibetan alpine meadow, with 0, 5, 10, and 15 g/m2 nitrogen addition treatments. Within the treatment plots, we arranged a total of 216 quadrats (of either 0.125 × 0.125 m, 0.25 × 0.25 m or 0.5 × 0.5 m size) to test how the sample area affects the relationship between plant species richness and foliar fungal disease severity. We found that the dilution effects were stronger in the 0.125 × 0.125 m and 0.25 × 0.25 m quadrats, compared with 0.5 × 0.5 m quadrats. There was a significant interaction between species richness and nitrogen addition in the 0.125 × 0.125 m and 0.25 × 0.25 m quadrats, indicating that a dilution effect was more easily observed under higher levels of nitrogen addition. Based on multigroup structural equation models, we found that even accounting for the direct impact of nitrogen addition (i.e., "nitrogen-disease hypothesis"), the dilution effect still worked at the 0.125 × 0.125 m scale. Overall, these findings suggest that spatial scale directly determines the occurrence of dilution effects, and can partly explain the observed variation in biodiversity-disease relationships in grasslands. Next-generation frameworks for predicting infectious diseases under rapid biodiversity loss scenarios need to incorporate spatial information.

Embryonic organizer formation disorder leads to multiorgan dysplasia in Down syndrome.

Despite the high prevalence of Down syndrome (DS) and early identification of the cause (trisomy 21), its molecular pathogenesis has been poorly understood and specific treatments have consequently been practically unavailable. A number of medical conditions throughout the body associated with DS have prompted us to investigate its molecular etiology from the viewpoint of the embryonic organizer, which can steer the development of surrounding cells into specific organs and tissues. We established a DS zebrafish model by overexpressing the human DYRK1A gene, a highly haploinsufficient gene located at the "critical region" within 21q22. We found that both embryonic organizer and body axis were significantly impaired during early embryogenesis, producing abnormalities of the nervous, heart, visceral, and blood systems, similar to those observed with DS. Quantitative phosphoproteome analysis and related assays demonstrated that the DYRK1A-overexpressed zebrafish embryos had anomalous phosphorylation of ß-catenin and Hsp90ab1, resulting in Wnt signaling enhancement and TGF-ß inhibition. We found an uncovered ectopic molecular mechanism present in amniocytes from fetuses diagnosed with DS and isolated hematopoietic stem cells (HSCs) of DS patients. Importantly, the abnormal proliferation of DS HSCs could be recovered by switching the balance between Wnt and TGF-ß signaling in vitro. Our findings provide a novel molecular pathogenic mechanism in which ectopic Wnt and TGF-ß lead to DS physical dysplasia, suggesting potential targeted therapies for DS.

Comparison of deep learning segmentation and multigrader-annotated mandibular canals of multicenter CBCT scans.

Deep learning approach has been demonstrated to automatically segment the bilateral mandibular canals from CBCT scans, yet systematic studies of its clinical and technical validation are scarce. To validate the mandibular canal localization accuracy of a deep learning system (DLS) we trained it with 982 CBCT scans and evaluated using 150 scans of five scanners from clinical workflow patients of European and Southeast Asian Institutes, annotated by four radiologists. The interobserver variability was compared to the variability between the DLS and the radiologists. In addition, the generalisation of DLS to CBCT scans from scanners not used in the training data was examined to evaluate its out-of-distribution performance. The DLS had a statistically significant difference (p < 0.001) with lower variability to the radiologists with 0.74 mm than the interobserver variability of 0.77 mm and generalised to new devices with 0.63 mm, 0.67 mm and 0.87 mm (p < 0.001). For the radiologists' consensus segmentation, used as a gold standard, the DLS showed a symmetric mean curve distance of 0.39 mm, which was statistically significantly different (p < 0.001) compared to those of the individual radiologists with values of 0.62 mm, 0.55 mm, 0.47 mm, and 0.42 mm. These results show promise towards integration of DLS into clinical workflow to reduce time-consuming and labour-intensive manual tasks in implantology.

Sex Differences in Protein Expression and Their Perturbations in Amniotic Fluid Cells of Down Syndrome Fetuses.

Down syndrome (DS) is the most common chromosomal condition associated with intellectual disability and is characterized by a variety of additional clinical findings. The pathogenesis of DS and the differences between the sexes are not clear. In order to identify differentially expressed proteins that might be employed as potential biological markers and elucidate the difference in pathogenesis between different genders of T21 fetuses, providing clues for individualized detection and treatment is essential. Amniocyte samples of T21 males, T21 females, CN males, and CN females were collected by amniocentesis. The quantitative value of the peptide corresponding to each sample was determined through quantitative analysis by mass spectrometry. We identified many differentially expressed proteins between T21 fetuses and CN fetuses/T21 males and CN males/T21 females and CN females/and T21 males and T21 females. These differential proteins are associated with many important biological processes and affect the development of multiple systems, including the heart, hematopoietic, immune, reproductive, and nervous systems. Our results show sex-specific modulation of protein expression and biological processes and provide new insights into sex-specific differences in the pathogenesis of DS.

Toxicology evaluation of overdose hydroxychloroquine on zebrafish (Danio rerio) embryos.

Potential risks of treatment with hydroxychloroquine (HCQ) include QT interval prolongation, hypoglycemia, a wide range of neuropsychiatric manifestations, hematotoxicity, and potential genetic defects. HCQ is extremely toxic when used in overdose and can lead to tachycardia, hypotension, known central nervous system, transmission defects, hypokalemia and other manifestations in individuals. The mechanism of excessive HCQ leading to these manifestations is still unclear. In this paper, overdose HCQ at different concentrations was used to treat zebrafish embryos, and the phenomena like human beings were obtained, such as increased heart rate and nervous system inhibition. With the increase of concentration to 100 µM, embryo mortality and malformation rate increased and hatching rate decreased, in situ hybridization showed abnormal differentiation of embryo germ layers and formation of vital organs. We selected embryos treated with 50 µM HCQ, in which concentration the mortality rate, hatching rate and malformation rate of the embryos were like those of the control group, for transcriptome analysis. Although the above indexes did not change significantly, the molecular changes related to the development of the heart, eye, nerve and other important organs were significant. This study provides useful information for further research on the toxicity mechanism of HCQ overdose, and provides some insight that can guide future studies in humans.

The key player in the pathogenesis of environmental influence of systemic lupus erythematosus: Aryl hydrocarbon receptor.

The aryl hydrocarbon receptor was previously known as an environmental receptor that modulates the cellular response to external environmental changes. In essence, the aryl hydrocarbon receptor is a cytoplasmic receptor and transcription factor that is activated by binding to the corresponding ligands, and they transmit relevant information by binding to DNA, thereby activating the transcription of various genes. Therefore, we can understand the development of certain diseases and discover new therapeutic targets by studying the regulation and function of AhR. Several autoimmune diseases, including systemic lupus erythematosus (SLE), have been connected to AhR in previous studies. SLE is a classic autoimmune disease characterized by multi-organ damage and disruption of immune tolerance. We discuss here the homeostatic regulation of AhR and its ligands among various types of immune cells, pathophysiological roles, in addition to the roles of various related cytokines and signaling pathways in the occurrence and development of SLE.

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.

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.

Topological phase change transistors based on tellurium Weyl semiconductor.

Modern electronics demand transistors with extremely high performance and energy efficiency. Charge-based transistors with conventional semiconductors experience substantial heat dissipation because of carrier scattering. Here, we demonstrate low-loss topological phase change transistors (TPCTs) based on tellurium, a Weyl semiconductor. By modulating the energy separation between the Fermi level and the Weyl point of tellurium through electrostatic gate modulation, the device exhibits topological phase change between Weyl (Chern number ≠ 0) and conventional (Chern number = 0) semiconductors. In the Weyl ON state, the device has low-loss transport characteristics due to the global topology of gauge fields against external perturbations; the OFF state exhibits trivial charge transport in the conventional phase by moving the Fermi level into the bandgap. The TPCTs show a high ON/OFF ratio (108) at low operation voltage (≤2 volts) and high ON-state conductance (39 mS/µm). Our studies provide alternative strategies for realizing ultralow power electronics.