Linker histone H1 drives heterochromatin condensation via phase separation in Arabidopsis.

In the eukaryotic nucleus, heterochromatin forms highly condensed, visible foci known as heterochromatin foci (HF). These HF are enriched with linker histone H1, a key player in heterochromatin condensation and silencing. However, it is unknown how H1 aggregates HF and condenses heterochromatin. In this study, we established that H1 facilitates heterochromatin condensation by enhancing inter- and intrachromosomal interactions between and within heterochromatic regions of the Arabidopsis (Arabidopsis thaliana) genome. We demonstrated that H1 drives HF formation via phase separation, which requires its C-terminal intrinsically disordered region (C-IDR). A truncated H1 lacking the C-IDR fails to form foci or recover HF in the h1 mutant background, whereas C-IDR with a short stretch of the globular domain (18 out of 71 amino acids) is sufficient to rescue both defects. In addition, C-IDR is essential for H1's roles in regulating nucleosome repeat length and DNA methylation in Arabidopsis, indicating that phase separation capability is required for chromatin functions of H1. Our data suggest that bacterial H1-like proteins, which have been shown to condense DNA, are intrinsically disordered and capable of mediating phase separation. Therefore, we propose that phase separation mediated by H1 or H1-like proteins may represent an ancient mechanism for condensing chromatin and DNA.

GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade.

During Hedgehog (Hh) signal transduction in development and disease, the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO) communicates with GLI transcription factors by binding the protein kinase A catalytic subunit (PKA-C) and physically blocking its enzymatic activity. Here, we show that GPCR kinase 2 (GRK2) orchestrates this process during endogenous mouse and zebrafish Hh pathway activation in the primary cilium. Upon SMO activation, GRK2 rapidly relocalizes from the ciliary base to the shaft, triggering SMO phosphorylation and PKA-C interaction. Reconstitution studies reveal that GRK2 phosphorylation enables active SMO to bind PKA-C directly. Lastly, the SMO-GRK2-PKA pathway underlies Hh signal transduction in a range of cellular and in vivo models. Thus, GRK2 phosphorylation of ciliary SMO and the ensuing PKA-C binding and inactivation are critical initiating events for the intracellular steps in Hh signaling. More broadly, our study suggests an expanded role for GRKs in enabling direct GPCR interactions with diverse intracellular effectors.

MORE FLORET1 controls anther development by negatively regulating key tapetal genes in both diploid and tetraploid rice.

Polyploid hybrid rice (Oryza sativa) has great potential for increasing yields. However, hybrid rice depends on male fertility and its regulation, which is less well studied in polyploid rice than in diploid rice. We previously identified an MYB transcription factor, MORE FLORET1 (MOF1), whose mutation causes male sterility in neo-tetraploid rice. MOF1 expression in anthers peaks at anther Stage 7 (S7) and progressively decreases to low levels at S10. However, it remains unclear how the dynamics of MOF1 expression contribute to male fertility. Here, we carefully examined anther development in both diploid and tetraploid mof1 rice mutants, as well as lines ectopically expressing MOF1 in a temporal manner. MOF1 mutations caused delayed degeneration of the tapetum and middle layer of anthers and aberrant pollen wall organization. Ectopic MOF1 expression at later stages of anther development led to retarded cytoplasmic reorganization of tapetal cells. In both cases, pollen grains were aborted and seed production was abolished, indicating that precise control of MOF1 expression is essential for male reproduction. We demonstrated that 5 key tapetal genes, CYP703A3 (CYTOCHROME P450 HYDROXYLASE 703A3), OsABCG26 (O. sativa ATP BINDING CASSETTE G26), PTC1 (PERSISTENT TAPETAL CELL1), PKS2 (POLYKETIDE SYNTHASE 2), and OsABCG15 (O. sativa ATP BINDING CASSETTE G15), exhibit expression patterns opposite to those of MOF1 and are negatively regulated by MOF1. Moreover, DNA affinity purification sequencing (DAP-seq), luciferase activity assays, and electrophoretic mobility shift assays indicated that MOF1 binds directly to the PKS2 promoter for transcriptional repression. Our results provide a mechanistic basis for the regulation of male reproduction by MOF1 in both diploid and tetraploid rice. This study will facilitate the development of polyploid male sterile lines, which are useful for breeding of polyploid hybrid rice.

Characterizing metabolomic signatures related to coffee and tea consumption and their association with incidence and dynamic progression of type 2 diabetes: A multi-state analysis.

Our study aimed to investigate the impact of tea and coffee consumption and related metabolomic signatures on dynamic transitions from diabetes-free status to incident type 2 diabetes (T2D), and subsequently to T2D-related complications and death. We included 438,970 participants in the UK Biobank who were free of diabetes and diabetes complications at baseline. Of these, 212,146 individuals had information on all metabolic biomarkers. We identified tea- and coffee-related metabolomic signatures using elastic net regression models. We examined associations of tea and coffee intake and related metabolomic signatures with the onset and progression of T2D using multi-state regression models. We observed that tea and coffee consumption and related metabolomic signatures were inversely associated with the risk of five T2D transitions. For example, HRs (95% CIs) per SD increase of the tea-related metabolomic signature were 0.87 (0.85, 0.89), 0.97 (0.95, 0.99), 0.91 (0.90, 0.92), 0.92 (0.91, 0.94), and 0.91 (0.90, 0.92) for transitions from diabetes-free state to incident T2D, from diabetes-free state to total death, from incident T2D to T2D complications, from incident T2D to death, and from T2D complications to death. These findings highlight the benefit of tea and coffee intake in reducing the risk of occurrence and progression of T2D.

Association of metabolic signatures of air pollution with MASLD: Observational and Mendelian randomization study.

BACKGROUND & AIMS: To identify metabolic signatures associated with exposure to ambient air pollution and to explore their associations with risk of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We utilized data from the UK Biobank Cohort. Annual mean concentrations of PM2.5, PM10, NO2 and NOx were assessed for each participant using bilinear interpolation. The Elastic Net regression model was used to identify metabolites associated with four air pollutants and to construct metabolic signatures, respectively. Associations between air pollutants, metabolic signatures and MASLD were analyzed using Cox models. Mendelian randomization (MR) analysis was used to examine potential causality. Mediation analysis was employed to examine the role of metabolic signatures in the association between air pollutants and MASLD. RESULTS: A total of 244,842 participants from the UK Biobank were included in this analysis. We identified 87, 65, 76, and 71 metabolites as metabolic signatures of PM2.5, PM10, NO2, and NOx, respectively. Metabolic signatures were associated with risk of MASLD, with hazard ratios (HRs) and 95% confidence intervals (95% CIs) were 1.10 (1.06, 1.14), 1.06 (1.02, 1.10), 1.24 (1.20, 1.29) and 1.14 (1.10, 1.19). The four pollutants were associated with increased risk of MASLD, with HRs (95% CIs) of 1.03 (1.01, 1.05), 1.02 (1.01, 1.04), 1.01 (1.01, 1.02) and 1.01 (1.00, 1.01). MR analysis indicated an association between PM2.5, NO2 and NOx-related metabolic signatures and MASLD. Metabolic signatures mediated the association of PM2.5, PM10, NO2 and NOx with MASLD. CONCLUSION: There may be association between PM2.5, PM10, NO2 and NOx-related metabolic signatures and MASLD, and metabolic signatures mediate the increase of PM2.5, PM10, NO2 and NOx in the risk of MASLD. IMPACT AND IMPLICATIONS: Air pollution is a significant public health issue and an important risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), however, the mechanism by which air pollution affects MASLD remains unclear. Our study used integrated serological metabolic data of 251 metabolites from a large-scale cohort study to demonstrate that metabolic signatures play a crucial role in the elevated risk of MASLD caused by air pollution. These results are relevant to patients and policymakers because they suggest that air pollution-related metabolic signatures are not only potentially associated with MASLD but also involved in mediating the process by which PM2.5, PM10, NO2, and NOx increase the risk of MASLD. Focusing on changes in air pollution-related metabolic signatures may offer a new perspective for preventing air pollution-induced MASLD and serve as protective measures to address this emerging public health challenge.

Research Progress of Human Biomimetic Self-Healing Materials.

Humans can heal themselves after injury, which inspires researchers to develop bionic self-healing materials. Such materials not only equipped with the self-repair capacities akin to those of the human body, but also emulate the mechanical properties of human organs, including the tensile resilience of muscles, the fatigue resistance of skin, and the elevated modulus typical of cartilage. Based on the design concept of imitating the structure of human organs, the bionic self-healing material perfectly solves the problem of poor mechanical properties of self-healing materials caused by weak bond energy and inter-chain flow. This review discusses various organ-inspired self-healing materials in detail, summarizes their synthetic principles and introduces their fascinating mechanical properties. Finally, the application prospects of bionic self-healing polymer materials, such as bio-strain sensors, self-healing anticorrosive coatings, biomedical detection, etc., are outlined. Considering the excellent comprehensive performance and multi-functions of human biomimetic self-healing polymers, more outstanding sustainable materials will be developed, accelerating research progress in self-healing materials and realizing environmentally friendly products in multiple fields.

In-Bridge Stereochemistry: A Determinant of Stapled Peptide Conformation and Activity.

Peptide side chain stapling has been proven to be an effective strategy for fine-tuning peptide properties. This innovative approach leads to the creation of stapled peptides characterized by stabilized α-helical conformations, enhanced protein-binding affinity, improved cell permeability, superior enzymatic stability, and numerous other advantages. Extensive research has explored the impact of various stapling bridges on the properties of these peptides, with limited investigation into the influence of bridge chirality, until very recently. In this concise review, we provide a brief overview of the current state of knowledge regarding the stereochemistry within the bridges of stapled peptides, offering insights into the potential applications of chiral bridges in the design and development of stapled peptides.

Inhibition of the RBMS1/PRNP axis improves ferroptosis resistance-mediated oxaliplatin chemoresistance in colorectal cancer.

The majority of patients with advanced colorectal cancer have chemoresistance to oxaliplatin, and studies on oxaliplatin resistance are limited. Our research showed that RNA-binding motif single-stranded interacting protein 1 (RBMS1) caused ferroptosis resistance in tumor cells, leading to oxaliplatin resistance. We employed bioinformatics to evaluate publically accessible data sets and discovered that RBMS1 was significantly upregulated in oxaliplatin-resistant colorectal cancer cells, in tandem with ferroptosis suppression. In vivo and in vitro studies revealed that inhibiting RBMS1 expression caused ferroptosis in colorectal cancer cells, restoring tumor cell sensitivity to oxaliplatin. Mechanistically, this is due to RBMS1 inducing prion protein translation, resulting in ferroptosis resistance in tumor cells. Validation of clinical specimens revealed that RBMS1 is similarly linked to tumor development and a poor prognosis. Overall, RBMS1 is a potential therapeutic target with clinical translational potential, particularly for oxaliplatin chemoresistance in colorectal cancer.

Relationship between metabolic status, physical activity and cardiovascular disease in participants with obesity.

OBJECTIVE: We aimed to investigate the independent and joint associations between metabolic status, PA (physical activity) and risk of CVD (cardiovascular disease) in participants with obesity. METHODS: We included 109,301 adults with obesity free of baseline CVD enrolled from 2006 to 2010 in the UK Biobank cohort (aged 56 ± 7.9 years). Based on metabolic status, obesity was grouped into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes; n = 26,989; BMI 33 ± 3.3 kg/m2) and metabolically unhealthy obesity (MUO; n = 82,312; BMI 34 ± 4.0 kg/m2). PA was categorized into four groups according to moderate-to-vigorous PA (MVPA): none, low, medium, and high. Multivariable Cox regression models were used for the main analyses adjusting for sociodemographic factors, lifestyles and comorbidities. RESULTS: There were 8,059 CVD events during a median follow-up of 8.1 years. MHO was associated with a 42% reduced risk of CVD compared with MUO (HR = 0.58, 95% CI: 0.53-0.63). A significant interaction effect between PA and metabolic status on CVD risk was found. Among MUO participants, individuals with PA had significantly decreased CVD risk when compared with no MVPA (HR = 0.87, 95% CI: 0.81-0.94 for low PA; HR = 0.85, 95% CI: 0.78-0.93 for medium PA; and HR = 0.86, 95% CI: 0.80-0.92 for high PA). The lowest CVD risk was observed in MHO & medium PA group when compared with MUO & no MVPA (HR = 0.45, 95% CI: 0.37-0.56). CONCLUSIONS: Both MHO and any MVPA were associated with reduced risk of CVD in adults with obesity, while PA could modify the relationship between metabolic status and CVD risk.

Recombinant human IL-37 attenuates acute cardiac allograft rejection in mice.

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.

Arabidopsis cryptochrome 1 controls photomorphogenesis through regulation of H2A.Z deposition.

Light is a key environmental cue that fundamentally regulates plant growth and development, which is mediated by the multiple photoreceptors including the blue light (BL) photoreceptor cryptochrome 1 (CRY1). The signaling mechanism of Arabidopsis thaliana CRY1 involves direct interactions with CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1)/SUPPRESSOR OF PHYA-105 1 and stabilization of COP1 substrate ELONGATED HYPOCOTYL 5 (HY5). H2A.Z is an evolutionarily conserved histone variant, which plays a critical role in transcriptional regulation through its deposition in chromatin catalyzed by SWR1 complex. Here we show that CRY1 physically interacts with SWC6 and ARP6, the SWR1 complex core subunits that are essential for mediating H2A.Z deposition, in a BL-dependent manner, and that BL-activated CRY1 enhances the interaction of SWC6 with ARP6. Moreover, HY5 physically interacts with SWC6 and ARP6 to direct the recruitment of SWR1 complex to HY5 target loci. Based on previous studies and our findings, we propose that CRY1 promotes H2A.Z deposition to regulate HY5 target gene expression and photomorphogenesis in BL through the enhancement of both SWR1 complex activity and HY5 recruitment of SWR1 complex to HY5 target loci, which is likely mediated by interactions of CRY1 with SWC6 and ARP6, and CRY1 stabilization of HY5, respectively.

Glucose metabolism disorder related to follicular fluid exosomal miR-122-5p in cumulus cells of endometriosis patients.

In Brief: Elevated expression of miR-122-5p in exosomes in the follicular fluid of patients with endometriosis impairs glucose metabolism in cumulus cells and may further impair oocyte quality. Abstract: Endometriosis (EMs) affects fertility in women of childbearing age in many ways. The underlying mechanisms, including the decrease in oocyte quality, require further investigation. Exosomes, small vesicles responsible for intercellular information exchange, have been found to be involved in many biological events, including follicle development and oocyte meiosis recovery. From the perspective of follicular fluid exosomes, this study aimed to elucidate the mechanisms involved in EMs-related oocyte quality decline. Follicular fluid was collected from three groups of women: the untreated EMs group (EMs_UT), the satisfactorily treated EMs group (EMs_ST), and the control group (Ctrl). Mouse cumulus-oocyte complexes (COCs) were co-cultured with exosomes extracted from follicular fluid during in vitro maturation. Oocyte quality and cumulus cell function were assessed. High-throughput sequencing of miRNA in exosomes was conducted. The function of differentially expressed miRNAs was studied by using SVOG human ovarian granulosa cells transfected with an miRNA mimic and inhibitor. It was found that the follicular fluid exosomes from patients with untreated EMs reduced both the rate of maturation and the quality of mouse oocytes. Overexpression of miR-122-5p in untreated EMs inhibited the translation of key aldolase enzymes related to glucose metabolism and partly impaired glucose metabolism in the cumulus cells of patients with endometriosis. miR-122-5p was also observed to reduce proliferation and increase apoptosis after cell transfection with an miR-122-5p mimic and inhibitor. Further experiments are needed to determine whether there are additional small molecules in the follicular fluid of patients with endometriosis that could be involved in damaging oocyte quality and to identify where harmful substances in follicular fluid exosomes are loaded.

Suppression of frequency-mixing effect for pm-level heterodyne interferometers based on "zero coupling" optical path length control.

Optical path length (OPL) noise resulting from stray light significantly constrains interferometry displacement measurements in the low-frequency band. This paper presents an analytical model considering the presence of stray light in heterodyne laser interferometers. Due to the cyclic nonlinear coupling effect, there will be some special OPLs of stray light, minimizing the frequency-mixing impact to zero. Consequently, we propose a noise suppression scheme that locks the OPL of stray light at the zero coupling point. Therefore, we significantly enhanced the interference displacement measurement noise within the low-frequency band. Experimental results show that the interferometer achieves a displacement noise level lower than 6 pm/Hz1/2 covering 1 mHz.

Interleukin-37 contributes to endometrial regenerative cell-mediated immunotherapeutic effect on chronic allograft vasculopathy.

BACKGROUND AIMS: Chronic allograft vasculopathy (CAV) remains a predominant contributor to late allograft failure after organ transplantation. Several factors have already been shown to facilitate the progression of CAV, and there is still an urgent need for effective and specific therapeutic approaches to inhibit CAV. Human mesenchymal-like endometrial regenerative cells (ERCs) are free from the deficiencies of traditional invasive acquisition methods and possess many advantages. Nevertheless, the exact immunomodulation mechanism of ERCs remains to be elucidated. METHODS: C57BL/6 (B6) mouse recipients receiving BALB/c mouse donor abdominal aorta transplantation were treated with ERCs, negative control (NC)-ERCs and interleukin (IL)-37-/-ERCs (ERCs with IL-37 ablation), respectively. Pathologic lesions and inflammatory cell infiltration in the grafts, splenic immune cell populations, circulating donor-specific antibody levels and cytokine profiles were analyzed on postoperative day (POD) 40. The proliferative capacities of Th1, Th17 and Treg subpopulations were assessed in vitro. RESULTS: Allografts from untreated recipients developed typical pathology features of CAV, namely endothelial thickening, on POD 40. Compared with untreated and IL-37-/-ERC-treated groups, IL-37-secreting ERCs (ERCs and NC-ERCs) significantly reduced vascular stenosis, the intimal hyperplasia and collagen deposition. IL-37-secreting ERCs significantly inhibited the proliferation of CD4+T cells, reduced the proportions of Th1 and Th17 cells, but increased the proportion of Tregs in vitro. Furthermore, in vitro results also showed that IL-37-secreting ERCs significantly inhibited Th1 and Th17 cell responses, abolished B-cell activation, diminished donor-specific antibody production and increased Treg proportions. Notably, IL-37-secreting ERCs remarkably downregulated the levels of pro-inflammatory cytokines (interferon-γ, tumor necrosis factor-α, IL-1ß, IL-6 and IL-17A) and increased IL-10 levels in transplant recipients. CONCLUSIONS: The knockdown of IL-37 dramatically abrogates the therapeutic ability of ERCs for CAV. Thus, this study highlights that IL-37 is indispensable for ERC-mediated immunomodulation for CAV and improves the long-term allograft acceptance.

Frizzled-9 triggers actin polymerization and activates mechano-transducer YAP to rescue simulated microgravity-induced osteoblast dysfunction.

Long-term spaceflight can result in bone loss and osteoblast dysfunction. Frizzled-9 (Fzd9) is a Wnt receptor of the frizzled family that is vital for osteoblast differentiation and bone formation. In the present study, we elucidated whether Fzd9 plays a role in osteoblast dysfunction induced by simulated microgravity (SMG). After 1-7 days of SMG, osteogenic markers such as alkaline phosphatase (ALP), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2) were decreased, accompanied by a decrease in Fzd9 expression. Furthermore, Fzd9 expression decreased in the rat femur after 3 weeks of hindlimb unloading. In contrast, Fzd9 overexpression counteracted the decrease in ALP, OPN, and RUNX2 induced by SMG in osteoblasts. Moreover, SMG regulated phosphorylated glycogen synthase kinase-3ß (pGSK3ß) and ß-catenin expression or sublocalization. However, Fzd9 overexpression did not affect pGSK3ß and ß-catenin expression or sublocalization induced by SMG. In addition, Fzd9 overexpression regulated protein kinase B also known as Akt and extracellular signal-regulated kinase (ERK) phosphorylation and induced F-actin polymerization to form the actin cap, press the nuclei, and increase nuclear pore size, thereby promoting the nuclear translocation of Yes-associated protein (YAP). Our study findings provide mechanistic insights into the role of Fzd9 in triggering actin polymerization and activating YAP to rescue SMG-induced osteoblast dysfunction and suggest that Fzd9 is a potential target to restore osteoblast function in individuals with bone diseases and after spaceflight.

The role of chemerin in the regulation of cGAS-STING pathway in gestational diabetes mellitus placenta.

Recent studies already confirmed that placenta mitochondrial dysfunction is associated with the progression of gestational diabetes mellitus (GDM). Besides, a possible relationship between adipokine chemerin and disulfide-bond A oxidoreductase-like protein (DsbA-L) had been revealed, whereas the potential interaction remains unclear. In addition, very little is still known about the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and its mechanisms of action in the context of GDM. The present study aims to investigate the underlying mechanism of cGAS-STING pathway and its regulatory relationship with chemerin in GDM. A total of 50 participants, including 25 cases of GDM patients and 25 pregnant women with normal glucose tolerance, were enrolled, and their placenta tissues at term labor were collected. Besides, an insulin resistance cell model was established on the human trophoblastic cell line to explore the molecular mechanism of chemerin on cGAS-STING pathway. Results showed that there were mitochondrial pathological changes in GDM placenta, accompanied by the decreased expression of DsbA-L, increased level of chemerin, and the activation of cGAS-STING pathway. In the insulin resistant cell model, overexpression of chemerin upregulated protein expression of DsbA-L, and recombinant chemerin presented time-dependent inhibition on the cGAS-STING pathway, but this effect was not dependent on DsbA-L. In conclusion, elevated chemerin is probably a protective mechanism, which may be a potential therapeutic strategy for GDM.

Practice effects of a breathing technique on pilots' cognitive and stress associated heart rate variability during flight operations.

Commercial pilots endure multiple stressors in their daily and occupational lives which are detrimental to psychological well-being and cognitive functioning. The Quick coherence technique (QCT) is an effective intervention tool to improve stress resilience and psychophysiological balance based on a five-minute paced breathing exercise with heart rate variability (HRV) biofeedback. The current research reports on the application of QCT training within an international airline to improve commercial pilots' psychological health and support cognitive functions. Forty-four commercial pilots volunteered in a one-month training programme to practise self-regulated QCT in day-to-day life and flight operations. Pilots' stress index, HRV time-domain and frequency-domain parameters were collected to examine the influence of QCT practice on the stress resilience process. The results demonstrated that the QCT improved psychophysiological indicators associated with stress resilience and cognitive functions, in both day-to-day life and flight operation settings. HRV fluctuations, as measured through changes in RMSSD and LF/HF, revealed that the resilience processes were primarily controlled by the sympathetic nervous system activities that are important in promoting pilots' energy mobilization and cognitive functions, thus QCT has huge potential in facilitating flight performance and aviation safety. These findings provide scientific evidence for implementing QCT as an effective mental support programme and controlled rest strategy to improve pilots' psychological health, stress management, and operational performance.

Cloning, heterologous expression, and molecular characterization of a highly active and stable non-specific endonuclease from Pseudomonas fluorescens.

Non-specific endonucleases can be used for the digestion of nucleic acids because they hydrolyze DNA/RNA into 3-5 base pairs (bp) length oligonucleotide fragments without strict selectivity. In this work, a novel non-specific endonuclease from Pseudomonas fluorescens (PfNuc) with high activities for both DNA and RNA was successfully cloned and expressed in Escherichia coli. The production of PfNuc in flask scale could be achieved to 1.73 × 106 U/L and 4.82 × 106 U/L for DNA and RNA by investigation of the culture and induction conditions. The characterization of PfNuc indicated that it was Mg2+-dependent and the catalytic activity was enhanced by 3.74 folds for DNA and 1.06 folds for RNA in the presence of 5 mM Mg2+. The specific activity of PfNuc for DNA was 1.44 × 105 U/mg at pH 8.0 and 40 °C, and 3.93 × 105 U/mg for RNA at pH 8.5 and 45 °C. The Km of the enzyme for both DNA and RNA was close to 43 µM. The Vmax was 6.40 × 105 U/mg and 1.11 × 106 U/mg for DNA and RNA, respectively. There was no observed activity loss when PfNuc was stored at 4 °C and - 20 °C after 28 days or 10 repeated freeze-thaw cycles at - 80 °C. Molecular docking revealed that PfNuc formed 17 and 19 hydrogen bonds with single-stranded RNA and double-stranded DNA, respectively. These results could explain the high activity and stability of PfNuc, suggesting its great potential applications in the industry and clinic.

Baicalin attenuates PD-1/PD-L1 axis-induced immunosuppression in piglets challenged with Glaesserella parasuis by inhibiting the PI3K/Akt/mTOR and RAS/MEK/ERK signalling pathways.

Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1ß, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3-CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases.

Psychological resilience-related functional connectomes predict creative personality.

Both psychological resilience and creativity are complex concepts that have positive effects on individual adaptation. Previous studies have shown overlaps between the key brain regions or brain functional networks related to psychological resilience and creativity. However, no direct experimental evidence has been provided to support the assumption that psychological resilience and creativity share a common brain basis. Therefore, the present study investigated the relationship between psychological resilience and creativity using neural imaging method with a machine learning approach. At the behavioral level, we found that psychological resilience was positively related to creative personality. Predictive analysis based on static functional connectivity (FC) and dynamic FC demonstrated that FCs related to psychological resilience could effectively predict an individual's creative personality score. Both the static FC and dynamic FC were mainly located in the default mode network. These results prove that psychological resilience and creativity share a common brain functional basis. These findings also provide insights into the possibility of promoting individual positive adaptation from negative events or situations in a creative way.