Human mesenchymal stromal cells ameliorate cisplatin-induced acute and chronic kidney injury via TSG-6.

Cisplatin is widely used in tumor chemotherapy, but nephrotoxicity is an unavoidable side effect of cisplatin. Several studies have demonstrated that mesenchymal stromal cells (MSCs) ameliorate cisplatin-induced kidney injury, but the underlying mechanisms are unknown. In this study, the cisplatin-induced kidney injury mouse model was established by subjecting a single intraperitoneal injection with cisplatin. One hour before cisplatin injection, the mice received human bone marrow MSCs (hBM-MSCs) with or without siRNA-transfection, recombinant human tumor necrosis factor-α-stimulated gene/protein 6 (rhTSG-6), or PBS through the tail vein. In addition, cisplatin-stimulated HK-2 cells were treated with hBM-MSCs or rhTSG-6. Human BM-MSCs treatment remarkably ameliorated cisplatin-induced acute and chronic kidney injury, as evidenced by significant reductions in serum creatinine (Scr), blood urea nitrogen, tubular injury, collagen deposition, α-smooth muscle actin accumulation, as well as inflammatory responses, and by remarkable increased anti-inflammatory factor expression and Treg cells infiltration in renal tissues. Furthermore, we found that only a few hBM-MSCs engrafted into damaged kidney and that the level of human TSG-6 in the serum of mice increased significantly following hBM-MSCs administration. Moreover, hBM-MSCs significantly increased the viability of damaged HK-2 cells and decreased the levels of inflammatory cytokines in the culture supernatant. However, the knockdown of the TSG-6 gene in hBM-MSCs significantly attenuated their beneficial effects in vivo and in vitro. On the contrary, treated with rhTSG-6 achieved similar beneficial effects of hBM-MSCs. Our results indicate that systemic administration of hBM-MSCs alleviates cisplatin-induced acute and chronic kidney injury in part by paracrine TSG-6 secretion.

Tailoring silk fibroin fibrous architecture by a high-yield electrospinning method for fast wound healing possibilities.

In this study, a novel array electrospinning collector was devised to generate two distinct regenerated silk fibroin (SF) fibrous membranes: ordered and disordered. Leveraging electrostatic forces during the electrospinning process allowed precise control over the orientation of SF fiber, resulting in the creation of membranes comprising both aligned and randomly arranged fiber layers. This innovative approach resulted in the development of large-area membranes featuring exceptional stability due to their alternating patterned structure, achievable through expansion using the collector, and improving the aligned fiber membrane mechanical properties. The study delved into exploring the potential of these membranes in augmenting wound healing efficiency. Conducting in vitro toxicity assays with adipose tissue-derived mesenchymal stem cells (AD-MSCs) and normal human dermal fibroblasts (NHDFs) confirmed the biocompatibility of the SF membranes. We use dual perspectives on exploring the effects of different conditioned mediums produced by cells and structural cues of materials on NHDFs migration. The nanofibers providing the microenvironment can directly guide NHDFs migration and also affect the AD-MSCs and NHDFs paracrine effects, which can improve the chemotaxis of NHDFs migration. The ordered membrane, in particular, exhibited pronounced effectiveness in guiding directional cell migration. This research underscores the revelation that customizable microenvironments facilitated by SF membranes optimize the paracrine products of mesenchymal stem cells and offer valuable physical cues, presenting novel prospects for enhancing wound healing efficiency.

Computational Insights into SARS-CoV-2 Main Protease Mutations and Nirmatrelvir Efficacy: The Effects of P132H and P132H-A173V.

Nirmatrelvir, a pivotal component of the oral antiviral Paxlovid for COVID-19, targets the SARS-CoV-2 main protease (Mpro) as a covalent inhibitor. Here, we employed combined computational methods to explore how the prevalent Omicron variant mutation P132H, alone and in combination with A173V (P132H-A173V), affects nirmatrelvir's efficacy. Our findings suggest that P132H enhances the noncovalent binding affinity of Mpro for nirmatrelvir, whereas P132H-A173V diminishes it. Although both mutants catalyze the rate-limiting step more efficiently than the wild-type (WT) Mpro, P132H slows the overall rate of covalent bond formation, whereas P132H-A173V accelerates it. Comprehensive analysis of noncovalent and covalent contributions to the overall binding free energy of the covalent complex suggests that P132H likely enhances Mpro sensitivity to nirmatrelvir, while P132H-A173V may confer resistance. Per-residue decompositions of the binding and activation free energies pinpoint key residues that significantly affect the binding affinity and reaction rates, revealing how the mutations modulate these effects. The mutation-induced conformational perturbations alter drug-protein local contact intensities and the electrostatic preorganization of the protein, affecting noncovalent binding affinity and the stability of key reaction states, respectively. Our findings inform the mechanisms of nirmatrelvir resistance and sensitivity, facilitating improved drug design and the detection of resistant strains.

Improper toy waste handling can harm human health via seafood consumption: A comprehensive health risk assessment of heavy metals.

Toy production has been increasing over the last few decades to meet the growing demands for toys across the globe, which has inevitably worsened the problem of toy waste. Given the lack of modern waste disposal facilities, rural villagers in many developing countries often discard and incinerate toy waste in backyards or riverbanks, which may release the pollutants from toys (e.g., heavy metals), contaminate the surrounding areas, and eventually threaten the health of residents. As such, this study examined the impact of improper toy waste handling on the nearby aquaculture site by measuring the contamination level of heavy metals (As, Cd, Cu, Pb, and Zn) in the sediment and seafood (crabs, shrimps, and fish). The health risk of heavy metals via seafood consumption was assessed in different groups of people (males, females, teenagers, and seniors). Results showed that the sediment and seafood at the aquaculture site were generally not contaminated with heavy metals (contamination factor and bioaccumulation factor <1). However, consuming the seafood cultured at this site, especially for crabs, could pose a health risk to humans due to As and Cd (hazard quotient > 1), irrespective of their age and gender. This risk could not be lowered by cooking, except As by boiling. Overall, we revealed that improper toy waste handling did not cause severe heavy metal pollution in the surrounding environment, but the consumption of contaminated seafood could still threaten human health. To safeguard public health, we propose that toy waste should be appropriately treated by the authorities concerned. In addition, consuming seafood with long culture periods (e.g., crabs) should be reduced to minimize the dietary intake of heavy metals and their associated health risk.

Peer relationships mediate the pathways from behavioral qualities to United States and Chinese children's loneliness.

Loneliness is a perceived deficit in social relationships that is nested within broader cultural meaning systems. This longitudinal study examined predictors of loneliness in Chinese and U.S. children with the hypothesis that peer relationship parameters (number of friends, social preference, and popularity) mediate the associations between behavior qualities and loneliness differently across countries. Fifth-grade Chinese (n = 576, Mage = 10.58 years) and U.S. (White, Black, Asian, n = 540; Mage = 10.23 years) children completed two waves of assessment within an academic year. Shyness and athletic competence more strongly predicted loneliness for U.S. children, and academic ability, and aggression more strongly predicted loneliness for Chinese children. Popularity was a mediator for U.S. children but not Chinese children.

TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection.

As both host and pathogen require iron for survival, iron is an important regulator of host-pathogen interactions. However, the molecular mechanism by which how the availability of iron modulates host innate immunity against bacterial infections remains largely unknown. Using the metazoan Caenorhabditis elegans as a model, we demonstrate that infection with a pathogenic bacterium Salmonella enterica serovar Typhimurium induces autophagy by inactivating the target of rapamycin (TOR). Although the transcripts of ftn-1 and ftn-2 encoding two H-ferritin subunits are upregulated upon S. Typhimurium infection, the ferritin protein is kept at a low level due to its degradation mediated by autophagy. Autophagy, but not ferritin, is required for defense against S. Typhimurium infection under normal circumstances. Increased abundance of iron suppresses autophagy by activating TOR, leading to an increase in the ferritin protein level. Iron sequestration, but not autophagy, becomes pivotal to protect the host from S. Typhimurium infection in the presence of exogenous iron. Our results show that TOR acts as a regulator linking iron availability with host defense against bacterial infection.

The association between negative emotion differentiation and emotion regulation flexibility in daily life.

Emotion differentiation emphasises labelling emotional experiences in a precise and context-sensitive way. Negative emotion differentiation (NED) has been found to be associated with mental health, where emotion regulation (ER) may act as a pathway. The current study aims to explore the association between NED and flexible ER implementation in daily life. Specifically, we examined how NED was associated with two aspects of ER flexibility: contextual synchrony and temporal ER variability. 101 college students (54% female; Mage = 20.24 years) reported their momentary emotions via a 7-day experience sampling protocol, and the intraclass correlation coefficients were calculated to reflect NED. In 10-day daily diaries, they also reported information about the most negative event during the day (i.e. event type, event intensity and ER goal) and how they regulated their emotions. The results revealed that individuals with high NED showed higher levels of synchrony between change in ER use and change in event type and ER goal. In addition, NED was positively associated with both within- and between-strategy variability in ER use. The results demonstrated that the ability to differentiate between negative emotions was related to higher ER flexibility, which shed new light on understanding the role of emotion differentiation in well-being.

Survival and infectivity of second-stage root-knot nematode Meloidogyne incognita juveniles depend on lysosome-mediated lipolysis.

Adaptation to nutrient deprivation depends on the activation of metabolic programs to use reserves of energy. When outside a host plant, second-stage juveniles (J2) of the root-knot nematode (Meloidogyne spp.), an important group of pests responsible for severe losses in the production of crops (e.g., rice, wheat, and tomato), are unable to acquire food. Although lipid hydrolysis has been observed in J2 nematodes, its role in fitness and the underlying mechanisms remain unknown. Using RNA-seq analysis, here, we demonstrated that in the absence of host plants, the pathway for the biosynthesis of polyunsaturated fatty acids was upregulated, thereby increasing the production of arachidonic acid in middle-stage J2 Meloidogyne incognita worms. We also found that arachidonic acid upregulated the expression of the transcription factor hlh-30b, which in turn induced lysosomal biogenesis. Lysosomes promoted lipid hydrolysis via a lysosomal lipase, LIPL-1. Furthermore, our data demonstrated that blockage of lysosomal lipolysis reduced both lifespan and locomotion of J2 worms. Strikingly, disturbance of lysosomal lipolysis resulted in a decline in infectivity of these juveniles on tomato roots. Our findings not only reveal the molecular mechanism of lipolysis in J2 worms but also suggest potential novel strategies for the management of root-knot nematode pests.

Natural nematicidal metabolites and advances in their biocontrol capacity on plant parasitic nematodes.

Covering: 2010 to 2021Natural nematicidal metabolites are important sources of nematode control. This review covers the isolation and structural determination of nematicidal metabolites from 2010 to 2021. We summarise chemical structures, bioactivity, metabolic regulation and biosynthesis of potential nematocides, and structure-activity relationship and application potentiality of natural metabolites in plant parasitic nematodes' biocontrol. In doing so, we aim to provide a comprehensive overview of the potential roles that natural metabolites can play in anti-nematode strategies.

Thermochromic Ni(II) Organometallics With High Optical Transparency and Low Phase-Transition Temperature for Energy-Saving Smart Windows.

Thermochromic smart windows with rational modulation in indoor temperature and brightness draw considerable interest in reducing building energy consumption, which remains a huge challenge to meet the comfortable responsive temperature and the wide transmittance modulation range from visible to near-infrared (NIR) light for their practical application. Herein, a novel thermochromic Ni(II) organometallic of [(C2 H5 )2 NH2 ]2 NiCl4 for smart windows is rationally designed and synthesized via an inexpensive mechanochemistry method, which processes a low phase-transition temperature of 46.3 °C for the reversible color evolution from transparent to blue with a tunable visible transmittance from 90.5% to 72.1%. Furthermore, cesium tungsten bronze (CWO) and antimony tin oxide (ATO) with excellent NIR absorption in 750-1500 and 1500-2600 nm are introduced in the [(C2 H5 )2 NH2 ]2 NiCl4 -based smart windows, realizing a broadband sunlight modulation of a 27% visible light modulation and more than 90% of NIR shielding ability. Impressively, these smart windows demonstrate stable and reversible thermochromic cycles at room temperature. Compared with the conventional windows in the field tests, these smart windows can significantly reduce the indoor temperature by 16.1 °C, which is promising for next-generation energy-saving buildings.

AoMedA has a complex regulatory relationship with AoBrlA, AoAbaA, and AoWetA in conidiation, trap formation, and secondary metabolism in the nematode-trapping fungus Arthrobotrys oligospora.

The asexual sporulation of filamentous fungi is an important mechanism for their reproduction, survival, and pathogenicity. In Aspergillus and several filamentous fungi, BrlA, AbaA, and WetA are the key elements of a central regulatory pathway controlling conidiation, and MedA is a developmental modifier that regulates temporal expression of central regulatory genes; however, their roles are largely unknown in nematode-trapping (NT) fungi. Arthrobotrys oligospora is a representative NT fungus, which can capture nematodes by producing adhesive networks (traps). Here, we characterized the function of AoMedA and three central developmental regulators (AoBrlA, AoAbaA, and AoWetA) in A. oligospora by gene disruption, phenotypic comparison, and multi-omics analyses, as these regulators are required for conidiation and play divergent roles in mycelial development, trap formation, lipid droplet accumulation, vacuole assembly, and secondary metabolism. A combined analysis of phenotypic traits and transcriptome showed that AoMedA and AoWetA are involved in the regulation of peroxisome, endocytosis, and autophagy. Moreover, yeast one-hybrid analysis showed that AoBrlA can regulate AoMedA, AoAbaA, and AoWetA, whereas AoMedA and AoAbaA can regulate AoWetA. Our results highlight the important roles of AoMedA, AoBrlA, AoAbaA, and AoWetA in conidiation, mycelia development, trap formation, and pathogenicity of A. oligospora and provide a basis for elucidating the relationship between conidiation and trap formation of NT fungi. IMPORTANCE Conidiation is the most common reproductive mode for many filamentous fungi and plays an essential role in the pathogenicity of fungal pathogens. Nematode-trapping (NT) fungi are a special group of filamentous fungi owing to their innate abilities to capture and digest nematodes by producing traps (trapping devices). Sporulation plays an important role in the growth and reproduction of NT fungi, and conidia are the basic components of biocontrol reagents for controlling diseases caused by plant-parasitic nematodes. Arthrobotrys oligospora is a well-known NT fungus and is a routinely used model fungus for probing the interaction between fungi and nematodes. In this study, the functions of four key regulators (AoMedA, AoBrlA, AoAbaA, and AoWetA) involved in conidiation were characterized in A. oligospora. A complex interaction between AoMedA and three central regulators was noted; these regulators are required for conidiation and trap formation and play a pleiotropic role in multiple intracellular activities. Our study first revealed the role of AoMedA and three central regulators in conidiation, trap formation, and pathogenicity of A. oligospora, which contributed to elucidating the regulatory mechanism of conidiation in NT fungi and helped in developing effective reagents for biocontrol of nematodes.

Thyroid-stimulating hormone regulates cardiac function through modulating HCN2 via targeting microRNA-1a.

Previous studies have found microRNA-1 (miR-1) and hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) may be involved in the pathogenesis of thyroid hormone (TH) induced cardiac hypertrophy. However, little is known about the role of miR-1 and HCN2 in thyroid stimulation hormone (TSH)-induced cardiac dysfunction. In order to investigate the molecular mechanisms of TSH induced cardiac dysfunction and the role of miR-1/HCN2 in that process, we evaluated the expression of miR-1a/HCN2 in the ventricular myocardium of hypothyroid mice and in TSH-stimulated H9c2 cardiomyocytes. Our data revealed that hypothyroidism mice had smaller hearts, ventricular muscle atrophy, and cardiac contractile dysfunction compared with euthyroid controls. The upregulation of miR-1a and downregulation of HCN2 were found in ventricular myocardium of hypothyroid mice and TSH-stimulated H9c2 cardiomyocytes, indicating that miR-1a and HCN2 may be involved in TSH-induced cardiac dysfunction. We also found that the regulation of miR-1a and HCN2 expression and HCN2 channel activity by TSH requires TSHR, while the regulation of HCN2 expression and HCN2 channel function by TSH requires miR-1a. Thus, our data revealed the potential mechanism of TSH-induced cardiac dysfunction and might shed new light on the pathological role of miR-1a/HCN2 in hypothyroid heart disease.

Nest box entrance hole size can influence nest site selection and nest defence behaviour in Japanese tits.

Birds have the ability to assess the risk of predation in their environment and adjust their antipredation strategies based on this risk information. However, whether nest site selection has effect on subsequent nest defence behaviour has not been studied. In this study, we aimed to determine whether the Japanese tit (Parus minor) exhibits a nest-box hole size preference and whether the entrance hole sizes of nest boxes influence the nest defence behaviour of tits. We hung nest boxes with three different entrance hole sizes (diameters: 6.5 cm, 4.5 cm and 2.8 cm) in our study sites and investigated which nest boxes were occupied by tits. In addition, by using dummy-presentation experiments, we observed the nest defence behaviours of tits that nested in boxes with 2.8 cm and 4.5 cm entrance holes towards common chipmunks (Tamias sibiricus, a small nest predator able to enter these holes) and Eurasian red squirrels (Sciurus vulgaris, a large nest predator unable to enter the 2.8 cm entrance hole). The tits that bred in nest boxes with 2.8 cm entrance holes exhibited more intense nest defence responses to chipmunks than to squirrels. In contrast, the tits that bred in nest boxes with 4.5 cm entrance holes exhibited similar nest defence responses to chipmunks and squirrels. Additionally, Japanese tits that bred in nest boxes with 2.8 cm entrance holes exhibited more intense behavioural responses to chipmunks than those that bred in nest boxes with 4.5 cm entrance holes. Our results suggested that Japanese tits prefer to occupy nest boxes with small holes for breeding and that nest-box characteristics influenced their nest defence behaviour.

A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Exposure to enrofloxacin affects the early development and metabolic system of juvenile American shad, as indicated by host metabolism and the environmental microbiome.

Enrofloxacin as a special fish medicine is widely used in aquaculture fishes in China. But the effect of enrofloxacin exposure to the gut of aquatic animals is still unclear. In our investigation, enrofloxacin (300 mg/kg feed) was experimentally exposed to the juvenile American shad for 7 days and monitored for alterations in metabolomic and transcriptomic responses. The results showed the similar subset of affected pathways (P-value < 0.05), but there were still many differences in the number of identified biomarkers (520 differentially expressed genes genes and 230 metabolites). Most gut metabolic profiles were related to oxidative stress, inflammation, and lipid metabolism. These multiomic results reveal the specific metabolic disruption by enrofloxacin altering many signaling pathways (P-value < 0.05), such as arginine and proline metabolism pathways, pyrimidine metabolism, the FoxO signaling pathway, and purine metabolism. In addition, the predicted functions of proteins analysis showed that enrofloxacin exposure in an aquaculture environment could prevent the occurrence of organic diseases, including Vibrio cholerae infection and bacterial toxins, in aquatic systems. This is the first research indicating that enrofloxacin affects the relationship between environmental microorganisms and intestinal metabolism, and a study of the ecotoxicity of enrofloxacin occurrences in the aquatic system is warranted.

Treatment of Asymptomatic Bacteriuria after Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: Asymptomatic bacteriuria (ASB) is prevalent in kidney transplant recipients (KTRs) and is hypothesized to heighten the risk of subsequent urinary tract infections (UTIs). Whether antibiotic treatment of ASB in KTRs is beneficial has not been elucidated. Materials and Methods: We carried out a systematic review and meta-analysis of all randomized controlled trials (RCTs) and quasi-RCTs that examined the merits of managing asymptomatic bacteriuria in KTRs. The primary outcomes were rates of symptomatic urinary tract infections (UTIs) and antimicrobial resistance. Results: Five studies encompassing 566 patients were included. No significant difference in symptomatic UTI rates was found between antibiotics and no treatment groups (relative risk (RR) 1.05, 95% confidence interval (CI) = 0.78-1.41), with moderate heterogeneity (I2 = 36%). Antibiotic treatment was found to present an uncertain risk for the development of drug-resistant strains (RR = 1.51, 95% CI = 0.95-2.40, I2 = 0%). In all trials, no significant difference between study arms was demonstrated regarding patient and graft outcomes, such as graft function, graft loss, hospitalization due to UTI, all-cause mortality, or acute rejection. Conclusions: The practice of screening and treating kidney transplant patients for asymptomatic bacteriuria does not curtail the incidence of future symptomatic UTIs, increase antimicrobial resistance, or affect graft outcomes. Whether early treatment of ASB after kidney transplantation (<2 months) is beneficial requires more RCTs.

Ric8 acts as a regulator of G-protein signalling required for nematode-trapping lifecycle of Arthrobotrys oligospora.

Resistance to inhibitors of cholinesterase 8 (Ric8) is a conserved guanine nucleotide exchange factor that is involved in the regulation of G-protein signalling in filamentous fungi. Here, we characterized an orthologous Ric8 (AoRic8) in Arthrobotrys oligospora by multi-omics analyses. The Aoric8 deletion (ΔAoric8) mutants lost an ability to produce traps essential for nematode predation, accompanied by a marked reduction in cAMP level. Yeast two-hybrid assay revealed that AoRic8 interacted with G-protein subunit Gα1. Moreover, the mutants were compromised in mycelia growth, conidiation, stress resistance, endocytosis, cellular components and intrahyphal hyphae. Revealed by transcriptomic analysis differentially upregulated genes in the absence of Aoric8 were involved in cell cycle, DNA replication and recombination during trap formation while downregulated genes were primarily involved in organelles, carbohydrate metabolism and amino acid metabolism. Metabolomic analysis showed that many compounds were markedly downregulated in ΔAoric8 mutants versus the wild-type strain. Our results demonstrated a crucial role for AoRic8 in the fungal growth, environmental adaption and nematode predation through control of cell cycle, organelle and secondary metabolism by G-protein signalling.

The cAMP-PKA signalling pathway regulates hyphal growth, conidiation, trap morphogenesis, stress tolerance, and autophagy in Arthrobotrys oligospora.

The cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signalling pathway is evolutionarily conserved in eukaryotes and plays a crucial role in defending against external environmental challenges, which can modulate the cellular response to external stimuli. Arthrobotrys oligospora is a typical nematode-trapping fungus that specializes in adhesive networks to kill nematodes. To elucidate the biological roles of the cAMP-PKA signalling pathway, we characterized the orthologous adenylate cyclase AoAcy, a regulatory subunit (AoPkaR), and two catalytic subunits (AoPkaC1 and AoPkaC2) of PKA in A. oligospora by gene disruption, transcriptome, and metabolome analyses. Deletion of Aoacy significantly reduced the levels of cAMP and arthrobotrisins. Results revealed that Aoacy, AopkaR, and AopkaC1 were involved in hyphal growth, trap morphogenesis, sporulation, stress resistance, and autophagy. In addition, Aoacy and AopkaC1 were involved in the regulation of mitochondrial morphology, thereby affecting energy metabolism, whereas AopkaC2 affected sporulation, nuclei, and autophagy. Multi-omics results showed that the cAMP-PKA signalling pathway regulated multiple metabolic and cellular processes. Collectively, these data highlight the indispensable role of cAMP-PKA signalling pathway in the growth, development, and pathogenicity of A. oligospora, and provide insights into the regulatory mechanisms of signalling pathways in sporulation, trap formation, and lifestyle transition.

YAP in epithelium senses gut barrier loss to deploy defenses against pathogens.

Pathogens commonly disrupt the intestinal epithelial barrier; however, how the epithelial immune system senses the loss of intestinal barrier as a danger signal to activate self-defense is unclear. Through an unbiased approach in the model nematode Caenorhabditis elegans, we found that the EGL-44/TEAD transcription factor and its transcriptional activator YAP-1/YAP (Yes-associated protein) were activated when the intestinal barrier was disrupted by infections with the pathogenic bacterium Pseudomonas aeruginosa PA14. Gene Ontology enrichment analysis of the genes containing the TEAD-binding sites revealed that "innate immune response" and "defense response to Gram-negative bacterium" were two top significantly overrepresented terms. Genetic inactivation of yap-1 and egl-44 significantly reduced the survival rate and promoted bacterial accumulation in worms after bacterial infections. Furthermore, we found that disturbance of the E-cadherin-based adherens junction triggered the nuclear translocation and activation of YAP-1/YAP in the gut of worms. Although YAP is a major downstream effector of the Hippo signaling, our study revealed that the activation of YAP-1/YAP was independent of the Hippo pathway during disruption of intestinal barrier. After screening 10 serine/threonine phosphatases, we identified that PP2A phosphatase was involved in the activation of YAP-1/YAP after intestinal barrier loss induced by bacterial infections. Additionally, our study demonstrated that the function of YAP was evolutionarily conserved in mice. Our study highlights how the intestinal epithelium recognizes the loss of the epithelial barrier as a danger signal to deploy defenses against pathogens, uncovering an immune surveillance program in the intestinal epithelium.

Regenerated Silk Nanofibers for Robust and Cyclic Adsorption-Desorption on Anionic Dyes.

In recent years, adsorption-based membranes have been widely investigated to remove and separate textile pollutants. However, cyclic adsorption-desorption to reuse a single adsorbent and clear scientific evidence for the adsorption-desorption mechanism remains challenging. Herein, silk nanofibers were used to assess the adsorption potential for the typical anionic dyes from an aqueous medium, and they show great potential toward the removal of acid dyes from the aqueous solution with an adsorption rate of ∼98% in a 1 min interaction. Further, we measured the filtration proficiency of a silk nanofiber membrane in order to propose a continuous mechanism for the removal of acid blue dye, and a complete rejection was observed with a maximum permeability rate of ∼360 ± 5 L·m-2·h-1. The Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy studies demonstrate that this fast adsorption occurs due to multiple interactions between the dye molecule and the adsorbent substrate. The as-prepared material also shows remarkable results in desorption. A 50-time cycle exhibits complete adsorption and desorption ability, which not only facilitates high removal aptitude but also produces less solid waste than other conventional adsorbents. Additionally, fluorescent 2-bromo-2-methyl-propionic acid (abbreviated as EtOxPY)-silk nanofibers can facilitate to illustrate a clear adsorption and desorption mechanism. Therefore, the above-prescribed results make electrospun silk nanofibers a suitable choice for removing anionic dyes in real-time applications.