Transfection of entomopathogenic Metarhizium species with a mycovirus confers hypervirulence against two lepidopteran pests.

Although most known viruses infecting fungi pathogenic to higher eukaryotes are asymptomatic or reduce the virulence of their host fungi, those that confer hypervirulence to entomopathogenic fungus still need to be explored. Here, we identified and studied a novel mycovirus in Metarhizium flavoviride, isolated from small brown planthopper (Laodelphax striatellus). Based on molecular analysis, we tentatively designated the mycovirus as Metarhizium flavoviride partitivirus 1 (MfPV1), a species in genus Gammapartitivirus, family Partitiviridae. MfPV1 has two double-stranded RNAs as its genome, 1,775 and 1,575 bp in size respectively, encapsidated in isometric particles. When we transfected commercial strains of Metarhizium anisopliae and Metarhizium pingshaense with MfPV1, conidiation was significantly enhanced (t test; P-value < 0. 01), and the significantly higher mortality rates of the larvae of diamondback moth (Plutella xylostella) and fall armyworm (Spodoptera frugiperda), two important lepidopteran pests were found in virus-transfected strains (ANOVA; P-value < 0.05). Transcriptomic analysis showed that transcript levels of pathogenesis-related genes in MfPV1-infected M. anisopliae were obviously altered, suggesting increased production of metarhizium adhesin-like protein, hydrolyzed protein, and destruxin synthetase. Further studies are required to elucidate the mechanism whereby MfPV1 enhances the expression of pathogenesis-related genes and virulence of Metarhizium to lepidopteran pests. This study presents experimental evidence that the transfection of other entomopathogenic fungal species with a mycovirus can confer significant hypervirulence and provides a good example that mycoviruses could be used as a synergistic agent to enhance the biocontrol activity of entomopathogenic fungi.

Barley GRIK1-SnRK1 kinases subvert a viral virulence protein to upregulate antiviral RNAi and inhibit infection.

Viruses often usurp host machineries for their amplification, but it remains unclear if hosts may subvert virus proteins to regulate viral proliferation. Here, we show that the 17K protein, an important virulence factor conserved in barley yellow dwarf viruses (BYDVs) and related poleroviruses, is phosphorylated by host GRIK1-SnRK1 kinases, with the phosphorylated 17K (P17K) capable of enhancing the abundance of virus-derived small interfering RNAs (vsiRNAs) and thus antiviral RNAi. Furthermore, P17K interacts with barley small RNA-degrading nuclease 1 (HvSDN1) and impedes HvSDN1-catalyzed vsiRNA degradation. Additionally, P17K weakens the HvSDN1-HvAGO1 interaction, thus hindering HvSDN1 from accessing and degrading HvAGO1-carried vsiRNAs. Importantly, transgenic expression of 17K phosphomimetics (17K5D ), or genome editing of SDN1, generates stable resistance to BYDV through elevating vsiRNA abundance. These data validate a novel mechanism that enhances antiviral RNAi through host subversion of a viral virulence protein to inhibit SDN1-catalyzed vsiRNA degradation and suggest new ways for engineering BYDV-resistant crops.

Genetically Encoded Lizard Color Divergence for Camouflage and Thermoregulation.

Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.

Southern rice black-streaked dwarf virus induces incomplete autophagy for persistence in gut epithelial cells of its vector insect.

Autophagy plays an important role in virus infection of the host, because viral components and particles can be degraded by the host's autophagy and some viruses may be able to hijack and subvert autophagy for its benefit. However, details on the mechanisms that govern autophagy for immunity against viral infections or benefit viral survival remain largely unknown. Plant reoviruses such as southern rice black-streaked dwarf virus (SRBSDV), which seriously threaten crop yield, are only transmitted by vector insects. Here, we report a novel mechanism by which SRBSDV induces incomplete autophagy by blocking autophagosome-lysosome fusion, resulting in viral accumulation in gut epithelial cells of its vector, white-backed planthopper (Sogatella furcifera). SRBSDV infection leads to stimulation of the c-Jun N-terminal kinase (JNK) signaling pathway, which further activates autophagy. Mature and assembling virions were found close to the edge7 of the outer membrane of autophagosomes. Inhibition autophagy leads to the decrease of autophagosomes, which resulting in impaired maturation of virions and the decrease of virus titer, whereas activation of autophagy facilitated virus titer. Further, SRBSDV inhibited fusion of autophagosomes and lysosomes by interacting with lysosomal-associated membrane protein 1 (LAMP1) using viral P10. Thus, SRBSDV not only avoids being degrading by lysosomes, but also further hijacks these non-fusing autophagosomes for its subsistence. Our findings reveal a novel mechanism of reovirus persistence, which can explain why SRBSDV can be acquired and transmitted rapidly by its insect vector.

Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial.

BACKGROUND: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. METHODS: This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. FINDINGS: Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2-54·1), 49·2 months (47·2-53·2) in the BCRi-naive group, and 49·7 months (47·4-54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8-41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8-39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. INTERPRETATION: These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. FUNDING: AbbVie.

Mapping Genetic Topography of Cortical Thickness and Surface Area in Neonatal Brains.

Adult twin neuroimaging studies have revealed that cortical thickness (CT) and surface area (SA) are differentially influenced by genetic information, leading to their spatially distinct genetic patterning and topography. However, the postnatal origins of the genetic topography of CT and SA remain unclear, given the dramatic cortical development from neonates to adults. To fill this critical gap, this study unprecedentedly explored how genetic information differentially regulates the spatial topography of CT and SA in the neonatal brain by leveraging brain magnetic resonance (MR) images from 202 twin neonates with minimal influence by the complicated postnatal environmental factors. We capitalized on infant-dedicated computational tools and a data-driven spectral clustering method to parcellate the cerebral cortex into a set of distinct regions purely according to the genetic correlation of cortical vertices in terms of CT and SA, respectively, and accordingly created the first genetically informed cortical parcellation maps of neonatal brains. Both genetic parcellation maps exhibit bilaterally symmetric and hierarchical patterns, but distinct spatial layouts. For CT, regions with closer genetic relationships demonstrate an anterior-posterior (A-P) division, while for SA, regions with greater genetic proximity are typically within the same lobe. Certain genetically informed regions exhibit strong similarities between neonates and adults, with the most striking similarities in the medial surface in terms of SA, despite their overall substantial differences in genetic parcellation maps. These results greatly advance our understanding of the development of genetic influences on the spatial patterning of cortical morphology.SIGNIFICANCE STATEMENT Genetic influences on cortical thickness (CT) and surface area (SA) are complex and could evolve throughout the lifespan. However, studies revealing distinct genetic topography of CT and SA have been limited to adults. Using brain structural magnetic resonance (MR) images of twins, we unprecedentedly discovered the distinct genetically-informed parcellation maps of CT and SA in neonatal brains, respectively. Each genetic parcellation map comprises a distinct spatial layout of cortical regions, where vertices within the same region share high genetic correlation. These genetic parcellation maps of CT and SA of neonates largely differ from those of adults, despite their highly remarkable similarities in the medial cortex of SA. These discoveries provide important insights into the genetic organization of the early cerebral cortex development.

Appropriate reduction of importin-α gene expression enhances yellow dwarf disease resistance in common wheat.

Barley yellow dwarf viruses (BYDVs) cause widespread damage to global cereal crops. Here we report a novel strategy for elevating resistance to BYDV infection. The 17K protein, a potent virulence factor conserved in BYDVs, interacted with barley IMP-α1 and -α2 proteins that are nuclear transport receptors. Consistently, a nuclear localization signal was predicted in 17K, which was found essential for 17K to be transported into the nucleus and to interact with IMP-α1 and -α2. Reducing HvIMP-α1 and -α2 expression by gene silencing attenuated BYDV-elicited dwarfism, accompanied by a lowered nuclear accumulation of 17K. Among the eight common wheat CRISPR mutants with two to four TaIMP-α1 and -α2 genes mutated, the triple mutant α1aaBBDD /α2AAbbdd and the tetra-mutant α1aabbdd /α2AAbbDD displayed strong BYDV resistance without negative effects on plant growth under field conditions. The BYDV resistance exhibited by α1aaBBDD /α2AAbbdd and α1aabbdd /α2AAbbDD was correlated with decreased nuclear accumulation of 17K and lowered viral proliferation in infected plants. Our work uncovers the function of host IMP-α proteins in BYDV pathogenesis and generates the germplasm valuable for breeding BYDV-resistant wheat. Appropriate reduction of IMP-α gene expression may be broadly useful for enhancing antiviral resistance in agricultural crops and other economically important organisms.

Genomic and biological characteristics of a novel leafhopper-transmitted marafivirus infecting Triticum aestivum.

Here, we report a novel wheat-infecting marafivirus, tentatively named "Triticum aestivum marafivirus" (TaMRV). The full-length genome sequence of TaMRV comprises 6,437 nucleotides, excluding the poly(A) tail. Pairwise sequence comparisons and phylogenetic analysis revealed that TaMRV may represent a novel species within the genus Marafivirus in the family Tymoviridae. We also observed a mass of isometric particles with a diameter of about 30 nm in ultrathin sections of infected wheat leaf tissue. In addition, the leafhopper Psammotettix alienus was identified as a vector for this virus. This is the first report of the occurrence of a wheat-infecting marafivirus.

ß-arrestin1 regulates astrocytic reactivity via Drp1-dependent mitochondrial fission: implications in postoperative delirium.

Postoperative delirium (POD) is a frequent and debilitating complication, especially amongst high risk procedures, such as orthopedic surgery. This kind of neurocognitive disorder negatively affects cognitive domains, such as memory, awareness, attention, and concentration after surgery; however, its pathophysiology remains unknown. Multiple lines of evidence supporting the occurrence of inflammatory events have come forward from studies in human patients' brain and bio-fluids (CSF and serum), as well as in animal models for POD. ß-arrestins are downstream molecules of guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). As versatile proteins, they regulate numerous pathophysiological processes of inflammatory diseases by scaffolding with inflammation-linked partners. Here we report that ß-arrestin1, one type of ß-arrestins, decreases significantly in the reactive astrocytes of a mouse model for POD. Using ß-arrestin1 knockout (KO) mice, we find aggravating effect of ß-arrestin1 deficiency on the cognitive dysfunctions and inflammatory phenotype of astrocytes in POD model mice. We conduct the in vitro experiments to investigate the regulatory roles of ß-arrestin1 and demonstrate that ß-arrestin1 in astrocytes interacts with the dynamin-related protein 1 (Drp1) to regulate mitochondrial fusion/fission process. ß-arrestin1 deletion cancels the combination of ß-arrestin1 and cellular Drp1, thus promoting the translocation of Drp1 to mitochondrial membrane to provoke the mitochondrial fragments and the subsequent mitochondrial malfunctions. Using ß-arrestin1-biased agonist, cognitive dysfunctions of POD mice and pathogenic activation of astrocytes in the POD-linked brain region are reduced. We, therefore, conclude that ß-arrestin1 is a promising target for the understanding of POD pathology and development of POD therapeutics.

Oxidative stress mediates the impact of heatwaves on survival, growth and immune status in a lizard.

Climate change often includes increases in the occurrence of extreme environmental events. Among these, heatwaves affect the pace of life and performance of wildlife, particularly ectothermic animals, owing to their low thermoregulatory abilities. However, the underlying mechanisms by which this occurs remain unclear. Evidence shows that heatwaves alter the redox balance of ectotherms, and oxidative stress is a major mediator of life-history trade-offs. Therefore, oxidative stress may mediate the effect of extreme thermal conditions on the life histories of ectotherms. To test this hypothesis, a 2 × 2 experiment was conducted to manipulate the redox balance (through a mitochondrial uncoupler that alleviates oxidative stress) of the desert toad-headed agama (Phrynocephalus przewalskii) exposed to heatwave conditions. We recorded lizard growth and survival rates and quantified their redox and immune statuses. In control lizards (unmanipulated redox balance), heatwave conditions decreased growth and survival and induced oxidative damage and immune responses. By contrast, lizards with alleviated oxidative stress showed close-to-normal growth, survival, and immune status when challenged with heatwaves. These results provide mechanistic insight into the role of oxidative stress in mediating the effects of extreme temperatures on ectothermic vertebrates, which may have major eco-evolutionary implications.

Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging.

MOTS-c is a peptide encoded by the short open reading frame of the mitochondrial 12S rRNA gene. It is significantly expressed in response to stress or exercise and translocated to the nucleus, where it regulates the expression of stress adaptation-related genes with antioxidant response elements (ARE). MOTS-c mainly acts through the Folate-AICAR-AMPK pathway, thereby influencing energy metabolism, insulin resistance, inflammatory response, exercise, aging and aging-related pathologies. Because of the potential role of MOTS-c in maintaining energy and stress homeostasis to promote healthy aging, especially in view of the increasing aging of the global population, it is highly pertinent to summarize the relevant studies. This review summarizes the retrograde signaling of MOTS-c toward the nucleus, the regulation of energy metabolism, stress homeostasis, and aging-related pathological processes, as well as the underlying molecular mechanisms.

Flavobacterium lacisediminis sp. nov., a bacterium isolated from lake sediment.

A taxonomic identification using polyphasic approach was performed on strain TH16-21T, which was isolated from the interfacial sediment of Taihu Lake, PR China. Strain TH16-21T was Gram-stain-negative, aerobic, rod-shaped and catalase-positive. Phylogenetic analysis based on the 16S rRNA gene and genomic sequences indicated that strain TH16-21T was classified within the genus of Flavobacterium. The 16S rRNA gene sequence of strain TH16-21T showed the highest similarity to Flavobacterium cheniae NJ-26T (98.9 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain TH16-21T and F. cheniae NJ-26T were 91.2 and 45.9 %, respectively. The respiratory quinone was menaquinone 6. The major cellular fatty acids (>10 %) comprised iso-C15 : 0, iso-C16 : 0, iso-C15 : 1 G and iso-C16 : 0 3-OH. The genomic DNA G+C content was 32.2 mol%. Phosphatidylethanolamine, six amino lipids and three phospholipids were the main polar lipids. Based on the phenotypic features and phylogenetic position, a novel species with the name Flavobacterium lacisediminis sp. nov. is proposed. The type strain is TH16-21T (=MCCC 1K04592T=KACC 22896T).

Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation.

With the advent of an aging society, the incidence of dementia is increasing, resulting in a vast burden on society. It is increasingly acknowledged that neuroinflammation is implicated in various neurological diseases with cognitive dysfunction such as Alzheimer's disease, multiple sclerosis, ischemic stroke, traumatic brain injury, and central nervous system infections. As an important neuroinflammatory factor, interleukin-33 (IL-33) is highly expressed in various tissues and cells in the mammalian brain, where it plays a role in the pathogenesis of a number of central nervous system conditions. Reams of previous studies have shown that IL-33 has both pro- and anti-inflammatory effects, playing dual roles in the progression of diseases linked to cognitive impairment by regulating the activation and polarization of immune cells, apoptosis, and synaptic plasticity. This article will summarize the current findings on the effects IL-33 exerts on cognitive function by regulating neuroinflammation, and attempt to explore possible therapeutic strategies for cognitive disorders based on the adverse and protective mechanisms of IL-33.

Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins.

Neuroligins are postsynaptic cell adhesion molecules that are relevant to many neurodevelopmental disorders. They are differentially enriched at the postsynapse and interact with their presynaptic ligands, neurexins, whose differential binding to neuroligins has been shown to regulate synaptogenesis, transmission, and other synaptic properties. The proper functioning of functional networks in the brain depends on the proper connection between neuronal synapses. Impaired synaptogenesis or synaptic transmission results in synaptic dysfunction, and these synaptic pathologies are the basis for many neurodevelopmental disorders. Deletions or mutations in the neuroligins genes have been found in patients with both autism and schizophrenia. It is because of the important role of neuroligins in synaptic connectivity and synaptic dysfunction that studies on neuroligins in the past have mainly focused on their expression in neurons. As studies on the expression of genes specific to various cells of the central nervous system deepened, neuroligins were found to be expressed in non-neuronal cells as well. In the central nervous system, glial cells are the most representative non-neuronal cells, which can also express neuroligins in large amounts, especially astrocytes and oligodendrocytes, and they are involved in the regulation of synaptic function, as are neuronal neuroligins. This review examines the mechanisms of neuron neuroligins and non-neuronal neuroligins in the central nervous system and also discusses the important role of neuroligins in the development of the central nervous system and neurodevelopmental disorders from the perspective of neuronal neuroligins and glial neuroligins.

The eggshell-matrix protein gene OC-17 is functionally lost in the viviparous Chinese crocodile lizard.

Thickness reduction or loss of the calcareous eggshell is one of major phenotypic changes in the transition from oviparity to viviparity. Whether the reduction of eggshells in viviparous squamates is associated with specific gene losses is unknown. Taking advantage of a newly generated high-quality genome of the viviparous Chinese crocodile lizard (Shinisaurus crocodilurus), we found that ovocleidin-17 gene (OC-17), which encodes an eggshell matrix protein that is essential for calcium deposition in eggshells, is not intact in the crocodile lizard genome. Only OC-17 transcript fragments were found in the oviduct transcriptome, and no OC-17 peptides were identified in the eggshell proteome of crocodile lizards. In contrast, OC-17 was present in the eggshells of the oviparous Mongolia racerunner (Eremias argus). Although the loss of OC-17 is not common in viviparous species, viviparous squamates show fewer intact eggshell-specific proteins than oviparous squamates. Our study implies that functional loss of eggshell-matrix protein genes may be involved in the reduction of eggshells during the transition from oviparity to viviparity in the crocodile lizard.

Complete genome sequence of a novel wheat-infecting polerovirus associated with yellowing dwarf disease in China.

A novel wheat-infecting polerovirus, tentatively named "wheat yellow dwarf virus" (WYDV), was identified from winter wheat in China using transcriptome sequencing (RNA-seq) combined with RT-PCR and RACE amplification. WYDV has a single-stranded RNA genome of 5,650 nucleotides (nt) and contains seven putative open reading frames (ORFs). WYDV was found to share the highest sequence identity with cereal yellow dwarf virus RPV (CYDV-RPV, genus Polerovirus), 71.1% for the nucleotide sequence of the whole genome, and 77.3% and 70.0% for the amino acid sequences of the coat protein (CP) and RNA-dependent RNA polymerase protein (RdRp), respectively. Phylogenetic analysis based on the complete genome and CP and RdRp amino acid sequences showed that WYDV is most closely related to the cereal-infecting poleroviruses CYDV-RPV, CYDV-RPS, and barley yellow dwarf virus-GPV. These data suggest that WYDV, which is associated with a newly emerging yellow dwarf disease in wheat fields in central China, should be classified as a new member of the genus Polerovirus.

Analysis of the Chinese Alligator TCRα/δ Loci Reveals the Evolutionary Pattern of Atypical TCRδ/TCRµ in Tetrapods.

Atypical TCRδ found in sharks, amphibians, birds, and monotremes and TCRµ found in monotremes and marsupials are TCR chains that use Ig or BCR-like variable domains (VHδ/Vµ) rather than conventional TCR V domains. These unconventional TCR are consistent with a scenario in which TCR and BCR, although having diverged from each other more than 400 million years ago, continue to exchange variable gene segments in generating diversity for Ag recognition. However, the process underlying this exchange and leading to the evolution of these atypical TCR receptor genes remains elusive. In this study, we identified two TCRα/δ gene loci in the Chinese alligator (Alligator sinensis). In total, there were 144 V, 154 Jα, nine Jδ, eight Dδ, two Cα, and five Cδ gene segments in the TCRα/δ loci of the Chinese alligator, representing the most complicated TCRα/δ gene system in both genomic structure and gene content in any tetrapod examined so far. A pool of 32 VHδ genes divided into 18 subfamilies was found to be scattered over the two loci. Phylogenetic analyses revealed that these VHδ genes could be related to bird VHδ genes, VHδ/Vµ genes in platypus or opossum, or alligator VH genes. Based on these findings, a model explaining the evolutionary pattern of atypical TCRδ/TCRµ genes in tetrapods is proposed. This study sheds new light on the evolution of TCR and BCR genes, two of the most essential components of adaptive immunity.

Differential Microbial Communities in Paddy Soils Between Guiyang Plateaus and Chengdu Basins Drive the Incidence of Rice Bacterial Diseases.

Southwest China has the most complex rice-growing regions in China. With great differences in topography, consisting mainly of basins and plateaus, ecological factors differ greatly between regions. In this study, bulk paddy soils collected from long-term rice fields in Chengdu (basins) and Guiyang (plateaus) were used to study the correlation between microbial diversity and the incidence of rice bacterial diseases. Results showed that the microbial community composition in paddy soils and the microbial functional categories differed significantly between basins and plateaus. They shared >70% of the dominant genera (abundance >1%), but the abundance of the dominant genera differed significantly. Functional analysis found that bulk paddy soils from Chengdu were significantly enriched in virulence factor-related genes; soils from Guiyang were enriched in biosynthesis of secondary metabolites, especially antibiotics. Correspondingly, Chengdu was significantly enriched in leaf bacterial pathogens Acidovorax, Xanthomonas, and Pseudomonas. Greenhouse experiments and correlation analysis showed that soil chemical properties had a greater effect on microbial community composition and positively correlated with the higher incidence of rice bacterial foot rot in Guiyang, whereas temperature had a greater effect on soil microbial functions and positively correlated with the higher severity index of leaf bacterial diseases in Chengdu. Our results provide a new perspective on how differences in microbial communities in paddy soils can influence the incidence of rice bacterial diseases in areas with different topographies.

Molecular Characteristics and Potent Immunomodulatory Activity of Fasciola hepatica Cystatin.

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-ß and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

FcRn is not the receptor mediating the transfer of serum IgG to colostrum in pigs.

In contrast to humans or rabbits, in which maternal IgG is transmitted to offspring prenatally via the placenta or the yolk sac, large domestic animals such as pigs, cows and sheep transmit IgG exclusively through colostrum feeding after delivery. The extremely high IgG content in colostrum is absorbed by newborns via the small intestine. Although it is widely accepted that the neonatal Fc receptor, FcRn, is the receptor mediating IgG transfer across both the placenta and small intestine, it remains unclear whether FcRn also mediates serum IgG transfer across the mammary barrier to colostrum/milk, especially in large domestic animals. In this study, using a FcRn knockout pig model generated with a CRISPR-Cas9-based approach, we clearly demonstrate that FcRn is not responsible for the IgG transfer from serum to colostrum in pigs, although like in other mammals, it is involved in IgG homeostasis and mediates IgG absorption in the small intestine of newborns.