Ephedra sinica polysaccharide regulate the anti-inflammatory immunity of intestinal microecology and bacterial metabolites in rheumatoid arthritis.

Introduction: Ephedra sinica polysaccharide (ESP) exerts substantial therapeutic effects on rheumatoid arthritis (RA). However, the mechanism through which ESP intervenes in RA remains unclear. A close correlation has been observed between enzymes and derivatives in the gut microbiota and the inflammatory immune response in RA. Methods: A type II collagen-induced arthritis (CIA) mice model was treated with Ephedra sinica polysaccharide. The therapeutic effect of ESP on collagen-induced arthritis mice was evaluated. The anti-inflammatory and cartilage-protective effects of ESP were also evaluated. Additionally, metagenomic sequencing was performed to identify changes in carbohydrate-active enzymes and resistance genes in the gut microbiota of the ESP-treated CIA mice. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to observe the levels of serum metabolites and short-chain fatty acids in the gut. Spearman's correlational analysis revealed a correlation among the gut microbiota, antibiotic-resistance genes, and microbiota-derived metabolites. Results: ESP treatment significantly reduced inflammation levels and cartilage damage in the CIA mice. It also decreased the levels of pro-inflammatory cytokines interleukin (IL)-6, and IL-1-ß and protected the intestinal mucosal epithelial barrier, inhibiting inflammatory cell infiltration and mucosal damage. Here, ESP reduced the TLR4, MyD88, and TRAF6 levels in the synovium, inhibited the p65 expression and pp65 phosphorylation in the NF-κB signaling pathway, and blocked histone deacetylase (HDAC1 and HDAC2) signals. ESP influenced the gut microbiota structure, microbial carbohydrate-active enzymes, and microbial resistance related to resistance genes. ESP increased the serum levels of L-tyrosine, sn-glycero-3-phosphocholine, octadecanoic acid, N-oleoyl taurine, and decreased N-palmitoyl taurine in the CIA mice. Conclusion: ESP exhibited an inhibitory effect on RA. Its action mechanism may be related to the ability of ESP to effectively reduce pro-inflammatory cytokines levels, protect the intestinal barrier, and regulate the interaction between mucosal immune systems and abnormal local microbiota. Accordingly, immune homeostasis was maintained and the inhibition of fibroblast-like synoviocyte (FLS) proliferation through the HDAC/TLR4/NF-κB pathway was mediated, thereby contributing to its anti-inflammatory and immune-modulating effects.

Neural mechanism of non-adaptive cognitive emotion regulation in patients with non-suicidal self-injury.

BACKGROUND: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. METHODS: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. RESULTS: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = -4.74, p < 0.01); refocusing on plans (t = -4.11, p < 0.01); positive reappraisal (t = -9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, pFDR < 0.05) and the rolandic operculum (t = -4.57, pFDR < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = -0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, "trans-synaptic signaling" (p < -log108) and "modulation of chemical synaptic transmission" (p < -log108) in both cells. CONCLUSIONS: People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623.

Changeable Active Sites by Pr Doping CuSA-TiO2 Photocatalyst for Excellent Hydrogen Production.

Photocatalytic water splitting for clean hydrogen production has been a very attractive research field for decades. However, the insightful understanding of the actual active sites and their impact on catalytic performance is still ambiguous. Herein, a Pr-doped TiO2-supported Cu single atom (SA) photocatalyst is successfully synthesized (noted as Cu/Pr-TiO2). It is found that Pr dopants passivate the formation of oxygen vacancies, promoting the density of photogenerated electrons on the CuSAs, and optimizing the electronic structure and H* adsorption behavior on the CuSA active sites. The photocatalytic hydrogen evolution rate of the obtained Cu/Pr-TiO2 catalyst reaches 32.88 mmol g-1 h-1, 2.3 times higher than the Cu/TiO2. Innovatively, the excellent catalytic activity and performance is attributed to the active sites change from O atoms to CuSAs after Pr doping is found. This work provides new insight for understanding the accurate roles of single atoms in photocatalytic water splitting.

First-episode psychiatric disorder risk from SARS-CoV-2 infection, a clinical analysis with Chinese psychiatric inpatients.

The extensive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout China in late 2022 has underscored the correlation between this virus and severe psychiatric disorders. Nevertheless, there remains a dearth of reported corresponding clinical and pathological features. Accordingly, we retrospectively reviewed the electronic medical records of psychiatric inpatients for seven days from early January 2023. Twenty-one inpatients who developed first-episode psychiatric disorders within two weeks after SARS-CoV-2 infection were recruited, while 24 uninfected the first-episode psychiatric inpatients were selected as controls. Comparative analyses of clinical manifestations, routine laboratory, and imaging examinations were performed. Our investigation revealed a 330% increase in first-episode psychiatric inpatients incidence after SARS-CoV-2 infection in 2023 compared to the preceding year without infections. Most cases exhibited psychiatric symptoms within a week of infection, resolving about two weeks with no residual symptoms after a three month. One-way ANOVA analysis between inpatients characterized by psychotic symptoms and hyperthermia was significant. Infected inpatients displayed elevated cytokine levels of interleukin-4, interleukin-8, and interferon-α, and decreased levels of eosinophils and basophils. These finding suggested that SARS-CoV-2 may contribute to the development of psychiatric disorders, likely mediated by the virus-induced inflammatory response and neuronal dysfunction in the context of psychological distress.

Design of antiviral AGO2-dependent short hairpin RNAs.

The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals. RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), which exhibits significant promise for antiviral therapy. AGO2-dependent shRNA (agshRNA) generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA. In this study, we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power. Using this model, we designed siRNA sequences targeting diverse RNA viruses, including human enterovirus A71 (EV71), Zika virus (ZIKV), dengue virus 2 (DENV2), mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and transformed them into agshRNAs. We validated the performance of our agshRNA design by evaluating antiviral efficacies of agshRNAs in cells infected with different viruses. Using the agshRNA targeting EV71 as an example, we showed that the anti-EV71 effect of agshRNA was more potent compared with the corresponding siRNA and shRNA. Moreover, the antiviral effect of agshRNA is dependent on AGO2-processed guide RNA, which can load into the RNA-induced silencing complex (RISC). We also confirmed the antiviral effect of agshRNA in vivo. Together, this work develops a novel antiviral strategy that combines machine learning-based algorithm with agshRNA design to custom design antiviral agshRNAs with high efficiency.

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications.

Diabetes mellitus is a prevalent disorder with multi-system manifestations, causing a significant burden in terms of disability and deaths globally. Angio-tensin receptor-neprilysin inhibitor (ARNI) belongs to a class of medications for treating heart failure, with the benefits of reducing hospitalization rates and mortality. This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications, discussing possible physiological and molecular mechanisms, with insights for future applications.

The Y locus encodes a REPRESSOR OF PHOTOSYNTHETIC GENES protein that represses carotenoid biosynthesis via interaction with APRR2 in carrot.

Little is known about the factors regulating carotenoid biosynthesis in roots. In this study, we characterized DCAR_032551, the candidate gene of the Y locus responsible for the transition of root color from ancestral white to yellow during carrot (Daucus carota) domestication. We show that DCAR_032551 encodes a REPRESSOR OF PHOTOSYNTHETIC GENES (RPGE) protein, named DcRPGE1. DcRPGE1 from wild carrot (DcRPGE1W) is a repressor of carotenoid biosynthesis. Specifically, DcRPGE1W physically interacts with DcAPRR2, an ARABIDOPSIS PSEUDO-RESPONSE REGULATOR2 (APRR2)-like transcription factor. Through this interaction, DcRPGE1W suppresses DcAPRR2-mediated transcriptional activation of the key carotenogenic genes phytoene synthase 1 (DcPSY1), DcPSY2, and lycopene ε-cyclase (DcLCYE), which strongly decreases carotenoid biosynthesis. We also demonstrate that the DcRPGE1W-DcAPRR2 interaction prevents DcAPRR2 from binding to the RGATTY elements in the promoter regions of DcPSY1, DcPSY2, and DcLCYE. Additionally, we identified a mutation in the DcRPGE1 coding region of yellow and orange carrots that leads to the generation of alternatively spliced transcripts encoding truncated DcRPGE1 proteins unable to interact with DcAPRR2, thereby failing to suppress carotenoid biosynthesis. These findings provide insights into the transcriptional regulation of carotenoid biosynthesis and offer potential target genes for enhancing carotenoid accumulation in crop plants.

The association between prealbumin concentration at admission and mortality in elderly patients with hip fractures: a cohort study.

Malnutrition is associated with complications and mortality in patients of hip fracture. Prealbumin may be more suitable than albumin to accurately predict the prognosis of hip fracture in elderly patients. We found that prealbumin concentration was nonlinearly associated with mortality in elderly patients with hip fracture, and an inflection point effect was observed. OBJECTIVE: To evaluate the association between prealbumin concentration at admission and mortality in elderly patients with hip fractures. METHODS: Elderly patients with hip fractures were screened between Jan 2015 and Sep 2019. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between prealbumin concentration at admission and mortality. All analyses were performed using EmpowerStats and the R software. RESULTS: This cohort study included 2387 patients who met the study criteria. The mean follow-up was 37.64 months. The prealbumin concentration was 162.67 ± 43.2 mg/L. Multivariate Cox regression showed that prealbumin concentration was associated with mortality in geriatric patients with hip fracture (hazard ratio [HR] = 0.95, 95% confidence intervals [CI]: 0.93-0.97, P < 0.0001). In addition, an inflection point effect was observed in the nonlinear association. The inflection point was 162.2 mg/L. If it is less than this inflection point, then every 10 mg/L increase in prealbumin was associated with a 7% reduction in the risk of death (HR = 0.93, 95%CI: 0.90-0.96, P < 0.0001). When greater than the inflection point, there was no difference in the risk of death (HR = 0.99, 95%CI: 0.95-1.03, P = 0.5127). CONCLUSION: The prealbumin concentrations at admission were nonlinearly associated with long-term mortality in geriatric hip fractures, and 162.2 mg/L could be considered a prognostic factor of mortality risk.

Six-orders-of-magnitude-spanning dispersion measurement via Kalman filtering-aided white-light interferometry.

Dispersion plays a great role in ultrafast laser oscillators, ultrashort pulse amplifiers, and many other nonlinear optical dynamics. Therefore, dispersion measurement is crucial for device characterization, system design and nonlinear dynamics investigation therein. In this work, we demonstrate a versatile approach, i.e., Kalman filtering-aided white-light interferometry, for group delay dispersion (GDD) characterization. Extended Kalman filter is adopted to track the cosine-like interferogram, and to eliminate the unintended bias and the envelope, providing a nearly ideal phase retrieval and GDD estimation. The measurement range could span from tens of fs2 to tens of ps2, with an uncertainty of about 0.1%, enabling precise GDD measurement for diverse optical components, ranging from a millimeter-thick glass slide to highly dispersive chirped fiber Bragg gratings. Benefited by the simplicity, convenient setup, and easy operation as well as relatively low cost, this approach would help photonic device characterization, dispersion management and nonlinear dynamics investigation in the laboratory and work plant.

CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus.

Microglia are the residential immune cells in the central nervous system. Their roles as innate immune cells and regulators of synaptic remodeling are critical to the development and the maintenance of the brain. Numerous studies have depleted microglia to elucidate their involvement in healthy and pathological conditions. PLX3397, a blocker of colony stimulating factor 1 receptor (CSF1R), is widely used to deplete mouse microglia due to its non-invasiveness and convenience. Recently, other small rodents, including Syrian hamsters (Mesocricetus auratus) and Mongolian gerbils (Meriones unguiculatus), have been recognized as valuable animal models for studying brain functions and diseases. However, whether microglia depletion via PLX3397 is feasible in these species remains unclear. Here, we administered PLX3397 orally via food pellets to hamsters and gerbils. PLX3397 successfully depleted gerbil microglia but had no effect on microglial density in hamsters. Comparative analysis of the CSF1R amino acid sequence in different species hints that amino acid substitutions in the juxtamembrane domain may potentially contribute to the inefficacy of PLX3397 in hamsters.

Development and mouse model evaluation of a new phage cocktail intended as an alternative to antibiotics for treatment of Staphylococcus aureus-induced bovine mastitis.

Bovine mastitis (BM) is a prevalent infectious disease in dairy herds worldwide, resulting in substantial economic losses. Staphylococcus aureus is a major cause of mastitis in animals, and its antibiotic resistance poses challenges for treatment. Recently, there has been a renewed interest in the development of alternative methods to antibiotic therapy, including bacteriophages (phages), for controlling bacterial infections. In this study, 2 lytic phages (designated as JDYN for vB_SauM_JDYN and JDF86 for vB_SauM_JDF86) were isolated from the cattle sewage effluent samples collected from dairy farms in Shanghai. The 2 phages have a broad bactericidal spectrum against Staphylococcus of various origins. Genomic and morphological analyses revealed that the 2 phages belonged to the Myoviridae family. Moreover, JDYN and JDF86 remained stable under a wide range of temperatures or pH and were almost unaffected in chloroform. In this study, we prepared a phage cocktail designated "PHC-1" which consisted of a 1:1:1 ratio of JDYN, JDF86 and SLPW (a previously characterized phage). PHC-1 showed the strongest bacteriolytic effect and the lowest frequency of emergence of bacteriophage insensitive mutants compared with monophages. The bovine mammary epithelial cells (MAC-T cells) and lactating mice mastitis model were used to evaluate the effectiveness of PHC-1 in vitro and in vivo, respectively. The results demonstrated that PHC-1 treatment significantly reduced bacterial load, alleviated inflammatory response, and improved mastitis pathology. Altogether, these results suggest that PHC-1 has the potential to treat S. aureus-induced bovine mastitis and that phage cocktails can combat antibiotic-resistant S. aureus infections.

The impact of thickness-related grain boundary migration on hole concentration and mobility of p-type transparent conducting CuI films.

CuI films present promising optoelectronic properties for transparent conductors. However, the high hole concentration in CuI films hinders the controllable modulation of hole mobility, limiting their application in low-dimensional thin-film transistors. In this study, CuI films were prepared through a Cu film iodination method at room temperature, and a systematic investigation was conducted on the modulation of hole concentration and mobility with varying film thickness. The films exhibited a zinc blende structure (γ-phase) with increasing grain size as the thickness increased. The transmittance and optical bandgap of the films decreased with increasing thickness. The correlation of vacancy concentration with changing film thickness was analyzed through photoluminescence spectroscopy, revealing the influence of grain boundary migration on vacancy formation. The reduction in film thickness diminishes the migration of CuI grain boundaries, consequently reducing the probability of Cu vacancy and I vacancy formation, resulting in diminished hole concentration and enhanced hole mobility and film conductivity. The film with a thickness of 20 nm demonstrated optimal performance, with a transmittance of 90%, hole concentration of 4.09 × 1017 cm-3, hole mobility of 506.50 cm2 V-1 s-1, and conductivity of 33.19 S cm-1. This work deepens the understanding of hole transport such as hole concentration and mobility modulation in CuI films, highlighting the importance of controlling grain boundary migration during the film growth process.

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1.

Respiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses. Cathepsin L (CTSL) and calpain-1 (CAPN1) are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response. Here, two peptidomimetic α-ketoamide compounds, 14a and 14b, were identified as potent dual target inhibitors against CTSL and CAPN1. The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of α-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1. Both showed potent and broad-spectrum anticoronaviral activities in vitro, and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern (VOCs) with EC50 values ranging from 0.80 to 161.7 nM in various cells. Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance. Moreover, 14a and 14b exhibited good oral pharmacokinetic properties in mice, rats and dogs, and favorable safety in mice. In addition, both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model. And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%. Further evaluation showed that 14a and 14b exhibited excellent anti-inflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia. Taken together, these results suggested that 14a and 14b are promising drug candidates, providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.

Phage cocktail superimposed disinfection: A ecological strategy for preventing pathogenic bacterial infections in dairy farms.

Bovine mastitis (BM) is mainly caused by bacterial infection that has a highly impact on dairy production, affecting both economic viability and animal well-being. A cross-sectional study was conducted in dairy farms to investigate the prevalence and antimicrobial resistance patterns of bacterial pathogens associated with BM. The analysis revealed that Staphylococcus (49%), Escherichia (16%), Pseudomonas (11%), and Klebsiella (6%) were the primary bacterial pathogens associated with mastitis. A significant proportion of Staphylococcus strains displayed multiple drug resistance. The use of disinfectants is an important conventional measure to control the pathogenic bacteria in the environment. Bacteriophages (Phages), possessing antibacterial properties, are natural green and effective disinfectants. Moreover, they mitigate the risk of generating harmful disinfection byproducts, which are commonly associated with traditional disinfection methods. Based on the primary bacterial pathogens associated with mastitis in the investigation area, a phage cocktail, named SPBC-SJ, containing seven phages capable of lysing S. aureus, E. coli, and P. aeruginosa was formulated. SPBC-SJ exhibited superior bactericidal activity and catharsis effect on pollutants (glass surface) compared to chemical disinfectants. Clinical trials confirmed that the SPBC-SJ-based superimposed disinfection group (phage combined with chemical disinfectants) not only cut down the dosage of disinfectants used, but significantly reduced total bacterial counts on the ground and in the feeding trough of dairy farms. Furthermore, SPBC-SJ significantly reduced the abundance of Staphylococcus and Pseudomonas in the environment of the dairy farm. These findings suggest that phage-based superimposed disinfection is a promising alternative method to combat mastitis pathogens in dairy farms due to its highly efficient and environmentally-friendly properties.

Na2S2O3 Catalyzed Three-Component Synthesis and Anti-Bacterial Activity of 3-Methyl-4-(hetero)arylmethylene isoxazole-5(4H)-ones.

An efficient and green method for synthesizing 3-methyl-4-(hetero) arylmethylene isoxazole-5(4H)-ones was developed using a recyclable and environmental-friendly catalyst, Na2S2O3, and 16 target compounds were successfully synthesized under the obtained optimal reaction condition. Using rifampicin as a positive control, the antibacterial activity of all synthesized compounds was tested by micro dilution method, among them, 3-methyl-4-[(2,4-dimethoxyphenyl) methylene]-isoxazole-5-one (4 m) presented wonderful antimicrobial activity, which may contribute to the development of anti-tuberculosis drugs.

Combined Immunoinformatics to Design and Evaluate a Multi-Epitope Vaccine Candidate against Streptococcus suis Infection.

Streptococcus suis (S. suis) is a zoonotic pathogen with multiple serotypes, and thus, multivalent vaccines generating cross-protection against S. suis infections are urgently needed to improve animal welfare and reduce antibiotic abuse. In this study, we established a systematic and comprehensive epitope prediction pipeline based on immunoinformatics. Ten candidate epitopes were ultimately selected for building the multi-epitope vaccine (MVSS) against S. suis infections. The ten epitopes of MVSS were all derived from highly conserved, immunogenic, and virulence-associated surface proteins in S. suis. In silico analyses revealed that MVSS was structurally stable and affixed with immune receptors, indicating that it would likely trigger strong immunological reactions in the host. Furthermore, mice models demonstrated that MVSS elicited high titer antibodies and diminished damages in S. suis serotype 2 and Chz infection, significantly reduced sequelae, induced cytokine transcription, and decreased organ bacterial burdens after triple vaccination. Meanwhile, anti-rMVSS serum inhibited five important S. suis serotypes in vitro, exerted beneficial protective effects against S. suis infections and significantly reduced histopathological damage in mice. Given the above, it is possible to develop MVSS as a universal subunit vaccine against multiple serotypes of S. suis infections.

Realization of the Giant Pyroelectric Response via Modulated Polar Structures.

Among pyroelectric materials, Bi0.5 Na0.5 TiO3 (BNT)-based relaxors are particularly noteworthy due to their significant polarization fluctuation near the depolarization temperature (Td ), resulting in a large pyroelectric response. What has been overlooked is the dynamic behavior of inherent polar structures, particularly the temperature-dependent evolution of polar nanoregions (PNRs), which significantly impacts the pyroelectric behavior. Herein, based on the large pyroelectric response origination (the ferroelectric-relaxor phase transition), the mixed nonergodic and ergodic relaxor (NR+ER) critical state is constructed, which is believed to trigger the easily fluctuating polarization state with excellent pyroelectric response. Composition engineering (with Li+ , Sr2+ , and Ta5+ ) strategically controls the relaxor process and modulates the dynamic behavior of inherent polar structures by the random field effect. The pyroelectric coefficient of more than 1441 µCm-2 K-1 at room temperature (RT), more than 9221 µCm-2 K-1 (RT), and ≈107911 µCm-2 K-1 (Td ) are achieved in the Li+ -doped sample, the Sr2+ -doped sample, and the (Li+ +Ta5+ ) co-doped sample, respectively. This work earns the highest RT pyroelectric coefficient in BNT-based relaxors, which is suitable for pyroelectric applications. Furthermore, it provides a strategy for modulating the pyroelectric performance of BNT-based relaxors.

Streptococcal arginine deiminase system defences macrophage bactericidal effect mediated by XRE family protein XtrSs.

The arginine deiminase system (ADS) has been identified in various bacteria and functions to supplement energy production and enhance biological adaptability. The current understanding of the regulatory mechanism of ADS and its effect on bacterial pathogenesis is still limited. Here, we found that the XRE family transcriptional regulator XtrSs negatively affected Streptococcus suis virulence and significantly repressed ADS transcription when the bacteria were incubated in blood. Electrophoretic mobility shift (EMSA) and lacZ fusion assays further showed that XtrSs directly bind to the promoter of ArgR, an acknowledged positive regulator of bacterial ADS, to repress ArgR transcription. Moreover, we provided compelling evidence that S. suis could utilize arginine via ADS to adapt to acid stress, while ΔxtrSs enhanced this acid resistance by upregulating the ADS operon. Moreover, whole ADS-knockout S. suis increased arginine and antimicrobial NO in the infected macrophage cells, decreased intracellular survival, and even caused significant attenuation of bacterial virulence in a mouse infection model, while ΔxtrSs consistently presented the opposite results. Our experiments identified a novel ADS regulatory mechanism in S. suis, whereby XtrSs regulated ADS to modulate NO content in macrophages, promoting S. suis intracellular survival. Meanwhile, our findings provide a new perspective on how Streptococci evade the host's innate immune system.