Rhein kills Actinobacillus pleuropneumoniae, reduces biofilm formation, and effectively treats bacterial lung infections in mice.

Background. Actinobacillus pleuropneumoniae, a member of the Pasteurellaceae family, is known for its highly infectious nature and is the primary causative agent of infectious pleuropneumonia in pigs. This disease poses a considerable threat to the global pig industry and leads to substantial economic losses due to reduced productivity, increased mortality rates, and the need for extensive veterinary care and treatment. Due to the emergence of multi-drug-resistant strains, Chinese herbal medicine is considered one of the best alternatives to antibiotics due to its unique mechanism of action and other properties. As a type of Chinese herbal medicine, Rhein has the advantages of a wide antibacterial spectrum and is less likely to develop drug resistance, which can perfectly solve the limitations of current antibacterial treatments.Methods. The killing effect of Rhein on A. pleuropneumoniae was detected by fluorescence quantification of differential expression changes of key genes, and scanning electron microscopy was used to observe the changes in A. pleuropneumoniae status after Rhein treatment. Establishing a mouse model to observe the treatment of Rhein after A. pleuropneumoniae infection.Results. Here, in this study, we found that Rhein had a good killing effect on A. pleuropneumoniae and that the MIC was 25 µg ml-1. After 3 h of action, Rhein (4×MIC) completely kills A. pleuropneumoniae and Rhein has good stability. In addition, the treatment with Rhein (1×MIC) significantly reduced the formation of bacterial biofilms. Therapeutic evaluation in a murine model showed that Rhein protects mice from A. pleuropneumoniae and relieves lung inflammation. Quantitative RT-PCR (Quantitative reverse transcription polymerase chain reaction is a molecular biology technique that combines both reverse transcription and polymerase chain reaction methods to quantitatively detect the amount of a specific RNA molecule) results showed that Rhein treatment significantly downregulated the expression of the IL-18 (Interleukin refers to a class of cytokines produced by white blood cells), TNF-α, p65 and p38 genes. Along with the downregulation of genes such as IL-18, it means that Rhein has an inhibitory effect on the expression of these genes, thereby reducing the activation of inflammatory cells and the production of inflammatory mediators. This helps reduce inflammation and protects tissue from further damage.Conclusions. This study reports the activity of Rhein against A. pleuropneumoniae and its mechanism, and reveals the ability of Rhein to treat A. pleuropneumoniae infection in mice, laying the foundation for the development of new drugs for bacterial infections.

Risk Factors for Hypoglycemia Among Neonates: A Prospective Cohort Study Among Pregnant People With Gestational Diabetes Mellitus.

OBJECTIVE: Neonatal hypoglycemia (NH) is the most frequent complication in neonates born to pregnant people with gestational diabetes mellitus (GDM) and an important cause of brain damage and death of neonates. We explored the risk factors for NH in neonates of pregnant people with GDM. METHODS: A prospective cohort study was conducted involving 322 pregnant people with GDM at the Guangzhou Women and Children's Medical Centre. Maternal sociodemographic, clinical, and biochemical data, as well as general characteristics of neonates, were collected to analyze their associations with NH in neonates of pregnant people with GDM. RESULTS: The incidence of NH among neonates of pregnant people with GDM was 19.57% (63/322). After adjustment for confounders, the factors significantly associated with an increased risk of NH were cesarean delivery (relative risk [RR] = 3.44; 95% confidence interval [CI], 1.83-6.45), red blood cell (RBC) count (RR = 2.19; 95% CI, 1.22-3.96), and 1-hour postprandial glucose (RR = 2.35; 95% CI, 1.23-4.46) during pregnancy, whereas later gestational age (RR = 0.58; 95% CI, 0.42-0.80) and multiparity (RR = 0.32; 95% CI, 0.16-0.66) were associated with a reduced risk of NH. CONCLUSION: Cesarean delivery, maternal 1-hour glucose of the oral glucose tolerance test, and increased RBC count of pregnant people with GDM are independent risk factors for NH, while later gestational age and multiparity are protective factors.

Serum Biomarkers Predicting Airway Remodeling in Severe Childhood Bronchial Asthma.

Objective: To analyze the relationship between serum Toll-like receptor 4 (TLR4) and soluble intercellular adhesion molecule-1 (sICAM-1) levels and airway remodeling in children with severe bronchial asthma (BA) and their predictive value for recurrence. Methods: A retrospective study was conducted to select the clinical data of 120 children with severe BA who were admitted to Northern Jiangsu People's Hospital from June 2022 to June 2023 and completed follow-up. Serum TLR4 and sICAM-1 were detected at admission. According to the recurrence during the follow-up period, the clinical data of the recurrent children were included in the recurrent group, and the clinical data of the non-recurrent children were included in the non-recurrent group. There were 55 children each in the recurrence group and the non-recurrence group. The baseline data of children with severe BA were statistically analyzed and compared. The correlation between serum TLR4 and sICAM-1 levels and airway remodeling in children with severe BA was analyzed by bivariate correlation Pearson (N). Binary logistic regression was used to analyze the relationship between serum TLR4, sICAM-1 levels, and recurrence in children with severe BA. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of serum TLR4 and sICAM-1 for recurrence in children with severe BA; R4.1.0 statistical software was used to draw the decision curve of serum TLR4 and sICAM-1 levels to predict the recurrence of severe BA in children with a high-risk threshold as abscissa and net return rate as ordinate. Results: Among the 120 children with severe BA, 46 cases recurred during the 1-year follow-up period, with a recurrence rate of 38.33 %. The proportion of premature delivery and children with allergic rhinitis in the recurrent group was higher than that in the non-recurrent group, and the levels of eosinophil count, TLR4, and sICAM-1 were higher than those in the non-recurrent group (P < .001). The levels of T/D and WA% in the recurrent group were higher than those in the non-recurrent group (P < .001). The results of bivariate correlation Pearson (N) analysis showed that serum TLR4 and sICAM-1 levels were positively correlated with T/D and WA% in children with severe BA (r >0, P < .001); the results of ROC curve showed that the AUC of serum TLR4, sICAM-1 and combined detection in predicting the recurrence of children with severe BA were all > 0.70, which had certain predictive value, and the combined detection was the highest. The decision curve was drawn. The results showed that the net rate of return of serum TLR4 and sICAM-1 in predicting the recurrence of children with severe BA was better than that of a single net rate of return in the range of 0.217~0.284 and 0.296~0.492. In the range of high-risk threshold 0.000-0.958, the net rate of return of serum TLR4 and sICAM-1 combined to predict the recurrence of severe BA children was > 0, which was of clinical significance. Conclusion: The serum TLR4 and sICAM-1 levels are closely related to airway remodeling and recurrence in children with severe BA, and their levels can effectively predict the risk of recurrence.

Clinical value of serum MMP-3 in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is defined as the progressive deterioration of renal parenchyma and decline in renal unit function. In the early stages of CKD(G1 + G2), symptoms are usually not obvious and cannot be effectively recognized on the basis of available clinical markers. Progression to the middle and late stages of CKD results in severe kidney damage with multiple complications causing adverse outcomes, including death. Therefore, the early diagnosis and monitoring of CKD is critical. Matrix metalloproteinase-3 (MMP-3), an extracellular matrix-degrading enzyme, plays an important role in kidney diseases. However, the clinical significance of serum MMP-3 levels in CKD has rarely been reported. METHODS: We quantified the serum MMP-3 levels of 237 patients with CKD and 96 healthy individuals by using a highly sensitive time-resolved fluorescence immunoassay and analyzed differences in MMP-3 levels among the stages of CKD and the correlations of these changes with clinical indicators. RESULTS: The serum MMP-3 concentrations of patients with CKD (171.76 ± 165.22 ng/mL) were significantly higher than those of healthy controls (34.05 ± 22.93 ng/mL; P < 0.0001). In CKD, serum MMP-3 levels were significantly correlated with estimated glomerular filtration rate (eGFR) (r =  - 0.5804, P < 0.0001), serum creatinine (CREA) (r = 0.5823, P < 0.0001), blood urea nitrogen (BUN) (r = 0.6106, P < 0.0001), and protein-to-creatinine ratio (r = 0.4992, P < 0.0001). Randomized forest analysis finds CREA, BUN, and MMP-3 most significant influences on CKD disease severity. The critical value of MMP-3 concentration of 40.39 ng/mL combined with eGFR was effective in diagnosing positive patients in the early (G1 + G2) stage of CKD and showed a positivity rate of 73.45 %. Moreover, in the early stages of CKD, patients with CKD who had serum MMP-3 concentration > 100 ng/mL had more severe renal impairment and inflammation than those with CKD who have lower serum MMP-3 concentrations. CONCLUSION: Elevated serum MMP-3 levels are correlated with decreased kidney function in CKD progression, and patients with concomitant inflammation may express high levels of serum MMP-3. Serum MMP-3 may assist eGFR in improving the diagnosis of patients with early CKD.

Establishment and Clinical Application in Stroke of a Serum Copeptin Time-Resolved Fluorescence Immunoassay.

The serum biomarker copeptin, an innovative and stable substitute biomarker of vasopressin, is associated with stroke. Therefore, establishing a highly sensitive time-resolved fluorescence immunoassay for copeptin (copeptin-TRFIA) is helpful to measure stroke and evaluate its value in clinical applications. Double antibody sandwich was used to establish copeptin-TRFIA. The established method was then assessed. Two coated and Eu3+-labeled copeptin monoclonal specific antibodies targeting different antigen epitopes were employed. The serum fluorescence counts of patients with stroke and healthy volunteers were detected by using the well-established copeptin-TRFIA. Serum copeptin levels were measured and analyzed statistically. The actual measurement linearity range of the proposed method was 0.13-44.66 ng/mL. Copeptin-TRFIA had the inter-assay coefficient of variation (CV) of 6.49%-9.08% and the intra-assay CV of 4.75%-7.77%. Patients with cerebral infarction (CI) and intracerebral hemorrhage (ICH) had significantly higher serum copeptin levels than healthy subjects. Copeptin concentrations in the serum of patients with stroke were significantly correlated with the scores of the National Institute for Healthy Stroke Scale (NIHSS) and modified Rankin Scale (mRS). A highly sensitive copeptin-TRFIA was successfully established. Serum copeptin has a certain value in the clinical diagnosis and prognosis of stroke.

Living Magnetotactic Microrobots Based on Bacteria with a Surface-Displayed CRISPR/Cas12a System for Penaeus Viruses Detection.

Bacterial microrobots are an emerging living material in the field of diagnostics. However, it is an important challenge to make bacterial microrobots with both controlled motility and specific functions. Herein, magnetically driven diagnostic bacterial microrobots are prepared by standardized and modular synthetic biology methods. To ensure mobility, the Mms6 protein is displayed on the surface of bacteria and is exploited for magnetic biomineralization. This gives the bacterial microrobot the ability to cruise flexibly and rapidly with a magnetization intensity up to about 18.65 emu g-1. To achieve the diagnostic function, the Cas12a protein is displayed on the bacterial surface and is used for aquatic pathogen nucleic acid detection. This allows the bacterial microrobot to achieve sensitive, rapid, and accurate on-site nucleic acid detection, with detection limits of 8 copies µL-1 for decapod iridescent virus 1 (DIV1) and 7 copies µL-1 for white spot syndrome virus (WSSV). In particular, the diagnostic results based on the bacterial microrobots remained consistent with the gold standard test results when tested on shrimp tissue. This approach is a flexible and customizable strategy for building bacterial microrobots, providing a reliable and versatile solution for the design of bacterial microrobots.

A bulk form Cu-based ferromagnetic semiconductor (La,Ba)(Cu,Mn)SO with the Curie temperature up to 170 K.

We report the ferromagnetism in a new bulk form Cu-based magnetic semiconductor (La,Ba)(Cu,Mn)SO, which is iso-structural to the prototypical iron-based 1111-type superconductor LaFeAsO. Starting from the parent compound LaCuSO, carriers are introduced via the substitutions of La for Ba while spins are introduced via the substitutions of Cu for Mn. Spins are mediated by carriers, which develops into the long range ferromagnetic ordering. The maximum Curie temperature [Formula: see text] reaches up to [Formula: see text] 170 K with the doping levels of 10% Ba and 5% Mn. By comparing to the (La,Sr)(Cu,Mn)SO where Sr and Mn are co-doped into LaCuSO, we demonstrate that negative chemical pressure would suppress the ferromagnetic ordering.

Okadaic Acid Detection through a Rapid and Sensitive Amplified Luminescent Proximity Homogeneous Assay.

Okadaic acid (OA), a marine biotoxin produced by microalgae, poses a significant threat to mariculture, seafood safety, and human health. The establishment of a novel, highly sensitive detection method for OA would have significant practical and scientific implications. Therefore, the purpose of this study was to develop an innovative approach for OA detection. A competitive amplified luminescent proximity homogeneous assay (AlphaLISA) was developed using the principle of specific antigen-antibody binding based on the energy transfer between chemiluminescent microspheres. The method was non-washable, sensitive, and rapid, which could detect 2 × 10-2-200 ng/mL of OA within 15 min, and the detection limit was 4.55 × 10-3 ng/mL. The average intra- and inter-assay coefficients of variation were 2.54% and 6.26%, respectively. Detection of the actual sample results exhibited a good correlation with high-performance liquid chromatography. In conclusion, a simple, rapid, sensitive, and accurate AlphaLISA method was established for detecting OA and is expected to significantly contribute to marine biotoxin research.

Enhanced Biodegradation of Methyl Orange Through Immobilization of Shewanella oneidensis MR-1 by Polyvinyl Alcohol and Sodium Alginate.

Shewanella oneidensis MR-1 has great potential for use in remediating azo dye pollution. Here, a new high-efficiency biodegradation method was developed utilizing S. oneidensis MR-1 immobilized by polyvinyl alcohol (PVA) and sodium alginate (SA). After determining the optimal immobilization conditions, the effects of various environmental factors on methyl orange (MO) degradation were analyzed. The biodegradation activity of the immobilized pellets was evaluated by analyzing the MO removal efficiency, and characterization was performed using scanning electron microscopy. The MO adsorption kinetics can be described using pseudo-second-order kinetics. Compared with free bacteria, the MO degradation rate of the immobilized S. oneidensis MR-1 increased from 41% to 92.6% after 21 days, suggesting that the immobilized bacteria performed substantially better and had more stable removal rates. These factors indicate the superiority of bacteria entrapment in addition to its easy application. This study demonstrates that the application of immobilized S. oneidensis MR-1 entrapped by PVA-SA can be used to establish a reactor with stable and high MO removal rates.

Establishment of 11-dehydro-thromboxane B2 time-resolved immunoassay and application in membranous nephropathy.

BACKGROUND: 11-Dehydro-thromboxane B2 (11-dehydro-TXB2) is the final stable metabolite of thromboxane A2 (TXA2) and is involved in thrombus formation. Patients with membranous nephropathy (MN) are prone to thromboembolism events. METHODS: Time-resolved fluorescence immunoassay (TRFIA) for 11-dehydro-TXB2 was established by indirect competitive method. The coated 11-dehydro-TXB2-BSA conjugate was used to bind the 11-dehydro-TXB2 antibody competitively to the 11-dehydro-TXB2 antigen in the samples, followed by Eu3+-labeled goat anti-mouse IgG antibody, to detect 11-dehydro-TXB2. This study measured 11-dehydro-TXB2 concentrations in serum samples from healthy individuals and patients with MN. RESULTS: The linear range of TRFIA was 16.38-2000 pg/mL, the sensitivity was 4.70 pg/mL, the average coefficients of variation from intra-assay and inter-assay were 3.50% and 4.95%, respectively, and the recovery was 99.38%. The serum level of 11-dehydro-TXB2 in patients with MN was significantly higher than that in healthy subjects (P < 0.05). The serum 11-dehydro-TXB2 concentration detected by TRFIA was highly consistent with that by ELISA (ρ = 0.900). DISCUSSION: This study successfully established a new highly sensitive method for the detection of 11-dehydro-TXB2 in serum. 11-Dehydro-TXB2 has great potential in evaluating the risk of thromboembolic events in patients with MN and is expected to be applied to other thromboembolic-related diseases.

Sensitive amplified luminescent proximity homogeneous assay for the quantitative detection of CA242.

We here developed a sensitive and stable amplified luminescent proximity homogeneous assay (AlphaLISA) method for fast quantification of CA242 in human serum. Donor and acceptor beads modified with carboxyl groups could be coupled with CA242 antibodies after activation in the AlphaLISA method. CA242 was rapidly detected by the double antibody sandwich immunoassay. The method yielded good linearity (>0.996) and detection range (0.16-400 U/mL). The intra-assay precisions of CA242-AlphaLISA were between 3.43% and 6.81% (< 10%), and the inter-assay precisions were between 4.06% and 9.56% (< 15%). The relative recoveries ranged from 89.61% to 107.29%. Detection time for the CA242-AlphaLISA method was only 20 min. Moreover, results of CA242-AlphaLISA and time-resolved fluorescence immunoassay had satisfactory correlation and consistency (ρ = 0.9852). The method was successfully applied to the analysis of human serum samples. Meanwhile, serum CA242 has a good detection value in the identification and diagnosis of pancreatic cancer and the monitoring of disease degree. Furthermore, the proposed AlphaLISA method is expected to be an alternative to traditional detection methods, laying a good foundation for the further development of kits to detect other biomarkers in future studies.

Highly conductive and tough polyacrylamide/sodium alginate hydrogel with uniformly distributed polypyrrole nanospheres for wearable strain sensors.

Conductive hydrogels have attracted widespread attention because of their integrated characteristics of being stretchable, deformable, adhesive, self-healable, and conductive. Herein, we report a highly conductive and tough double-network hydrogel based on a double cross-linked polyacrylamide (PAAM) and sodium alginate (SA) network with conducting polypyrrole nanospheres (PPy NSs) uniformly distributed in the network (PAAM-SA-PPy NSs). SA was employed as a soft template for synthesis of PPy NSs and distribution of PPy NSs uniformly in the hydrogel matrix to construct SA-PPy conductive network. The PAAM-SA-PPy NS hydrogel exhibited both high electrical conductivity (6.44 S/m) and excellent mechanical properties (tensile strength of 560 kPa at 870 %), as along as high toughness, high biocompatibility, good self-healing and adhesion properties. The assembled strain sensors showed high sensitivity and a wide sensing range (a gauge factor of 1.89 for 0-400 % strain and 4.53 for 400-800 % strain, respectively), as well as fast responsiveness and reliable stability. When used as a wearable strain sensor, it was able to monitor a series of physical signals from human large-scale joint motions and subtle muscle movements. This work provides a new strategy for the development of electronic skins and flexible strain sensors.

Photo-Fenton self-cleaning carbon fibers membrane supported with Zr-MOF@Fe2O3 for effective phosphate removal from algae-rich water.

Adsorbents featuring abundant binding sites and high affinity to phosphate have been used to resolve water eutrophication. However, most of the developed adsorbents were focused on improving the adsorption ability of phosphate but ignored the effect of biofouling on the adsorption process especially used in the eutrophic water body. Herein, a novel MOF-supported carbon fibers (CFs) membrane with high regeneration and antifouling capability, was prepared by in-situ synthesis of well-dispersed MOF on CFs membrane, to remove phosphate from algae-rich water. The hybrid UiO-66-(OH)2@Fe2O3@CFs membrane exhibits a maximum adsorption capacity of 333.3 mg g-1 (pH 7.0) and excellent selectivity for phosphate sorption over coexisting ions. Moreover, the Fe2O3 nanoparticles anchored on the surface of UiO-66-(OH)2 through 'phenol-Fe(III)' reaction can endow the membrane with the robust photo-Fenton catalytic activity, which improves long-term reusability even under algae-rich condition. After 4 times photo-Fenton regenerations, the regeneration efficiency of the membrane could remain 92.2%, higher than that of hydraulic cleaning (52.6%). Moreover, the growth of C. pyrenoidosa was significantly reduced by 45.8% within 20 days via metabolism inhibition due to membrane-induced P-deficient conditions. Hence, the developed UiO-66-(OH)2@Fe2O3@CFs membrane holds significant prospects for large-scale application in phosphate sequestration of eutrophic water bodies.

G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

Development of Crosslinker-Free Polysaccharide-Lysozyme Microspheres for Treatment Enteric Infection.

Antibiotic abuse in the conventional treatment of microbial infections, such as inflammatory bowel disease, induces cumulative toxicity and antimicrobial resistance which requires the development of new antibiotics or novel strategies for infection control. Crosslinker-free polysaccharide-lysozyme microspheres were constructed via an electrostatic layer-by-layer self-assembly technique by adjusting the assembly behaviors of carboxymethyl starch (CMS) on lysozyme and subsequently outer cationic chitosan (CS) deposition. The relative enzymatic activity and in vitro release profile of lysozyme under simulated gastric and intestinal fluids were investigated. The highest loading efficiency of the optimized CS/CMS-lysozyme micro-gels reached 84.9% by tailoring CMS/CS content. The mild particle preparation procedure retained relative activity of 107.4% compared with free lysozyme, and successfully enhanced the antibacterial activity against E. coli due to the superposition effect of CS and lysozyme. Additionally, the particle system showed no toxicity to human cells. In vitro digestibility testified that almost 70% was recorded in the simulated intestinal fluid within 6 h. Results demonstrated that the cross-linker-free CS/CMS-lysozyme microspheres could be a promising antibacterial additive for enteric infection treatment due to its highest effective dose (573.08 µg/mL) and fast release at the intestinal tract.

An overview of biochemical technologies for the cancer biomarker miR-21 detection.

In recent years, the incidence of cancer has continuously increased, in which various miRNAs have been proposed as biomarkers for the early screening of cancer patients. As a consequence, the development of accurate methods for miRNA quantification has become a major research challenge worldwide. As one of the first discovered oncogenic miRNAs, microRNA-21 (miR-21) has been highlighted for its critical role in cancers. This review describes the main techniques currently available for miR-21 detection, compares the differences of the methods and the amplification strategies, and provides an overview of the state of knowledge in the field.

Antimicrobial Peptide MPX with Broad-Spectrum Bactericidal Activity Promotes Proper Abscess Formation and Relieves Skin Inflammation.

Bacteria have developed antibiotic resistance during the large-scale use of antibiotics, and multidrug-resistant strains are common. The development of new antibiotics or antibiotic substitutes has become an important challenge for humankind. MPX is a 14 amino acid peptide belonging to the MP antimicrobial peptide family. In this study, the antibacterial spectrum of the antimicrobial peptide MPX was first tested. The antimicrobial peptide MPX was tested for antimicrobial activity against the gram-positive bacterium S. aureus ATCC 25923, the gram-negative bacteria E. coli ATCC 25922 and Salmonella enterica serovar Typhimurium CVCC541, and the fungus Candida albicans ATCC 90029. The results showed that MPX had good antibacterial activity against the above four strains, especially against E. coli, for which the MIC was as low as 15.625 µg/mL. The study on the bactericidal mechanism of the antimicrobial peptide revealed that MPX can destroy the integrity of the cell membrane, increase membrane permeability, and change the electromotive force of the membrane, thereby allowing the contents to leak out and mediating bacterial death. A mouse acute infection model was used to evaluate the therapeutic effect of MPX after acute infection of subcutaneous tissue by S. aureus. The study showed that MPX could promote tissue repair in S. aureus infection and alleviate lung damage caused by S. aureus. In addition, skin H&E staining showed that MPX treatment facilitated the formation of appropriate abscesses at the subcutaneous infection site and facilitated the clearance of bacteria by the skin immune system. The above results show that MPX has good antibacterial activity and broad-spectrum antibacterial potential and can effectively prevent the invasion of subcutaneous tissue by S. aureus, providing new ideas and directions for the immunotherapy of bacterial infections.

A2AR limits IL-15-induced generation of CD39+ NK cells with high cytotoxicity.

CD39-mediated inhibition of natural killer (NK) cell activity has been demonstrated, but the characteristics of CD39+ NK cells in humans are not known. We investigated the characteristics of human circulating CD39+ NK cells. In healthy donors, the proportion of circulating CD39+ NK cells in total NK cells was relatively low compared with that of CD39- NK cells. Nonetheless, a higher proportion of CD39+ NK cells expressed CD107a. Similarly, a higher proportion of CD39+ NK cells expressed CD107a in patients with hepatitis B virus or patients with hepatocellular carcinoma. Stimulation with NK-sensitive K562 cells or interleukin (IL)-12/IL-18 activated CD39+ NK cells to express higher levels of CD107a, IFN-γ and TNF-α, relative to CD39- NK cells. Importantly, IL-15 induced the generation of CD39+ NK cells. In contrast, A2A adenosine receptor (A2AR) ligation suppressed the generation of CD39+ NK cells by inhibiting IL-15 signaling. These data for the first time demonstrated that A2AR counteracts IL-15-induced generation of human CD39+ NK cells, which have a stronger cytotoxicity than CD39- NK cells. IL-15-induced human CD39+ NK cells might be better choice for immunotherapy based on adoptive transfer of NK cells.

Poly(aspartic acid)-based self-healing hydrogel with precise antibacterial ability for rapid infected-wound repairing.

The development of wound dressings with antibacterial activities and simultaneous pro-healing functions are always urgent in treating bacterial wound infection. Herein, a novel multifunctional self-healing hydrogel was designed and prepared by crosslinking quaternary ammonium/boronic acid modified poly(aspartic acid) and poly (vinyl alcohol) polymers with targeted peptide MP196- conjugated polydopamine. The formation of this hydrogel not only improves the biocompatibility of quaternary poly(aspartic acid), but also enhances antibacterial efficacy by pH-triggering dissociation under the low pH bacterial microenvironment. Moreover, precise photothermal treatment can be achieved. In vitro study suggested high synergistic antibacterial efficiency(∼100 %) under near-infrared light, significantly higher than a single antibacterial strategy (66.0-82.6 %). In vivo study suggested infected wounds treated with the hydrogel showed an optimal healing rate(92.0 %) after 7 days. The survival rate of the bacteria in the epidermal tissues was reduced to 2.3 %. Besides, the suitable self-healing property of this hydrogel facilitated its application in the diversity of wound shapes. Thus, the novel poly(aspartic acid) hydrogel might be a promising candidate for precise therapy of bacteria-infected wounds.

Development of amplified luminescent proximity homogeneous assay for quantitation of gastrin-17.

A highly sensitive and convenient amplified luminescent proximity homogeneous assay (AlphaLISA) method with high throughput and automation potential was developed for quantitation of serum Gastrin-17 (G-17) levels, which can facilitate the early diagnosis of atrophic gastritis in people at high risk of gastric cancer using a non-invasive approach. In this study, donor and acceptor beads with modified carboxyl groups on the surface were directly coupled to anti-G-17 antibodies through activation was proposed for application in the development of the new AlphaLISA, which can effectively simplify the steps and shorten the reaction time to achieve faster detection. Therefore, the G-17-AlphaLISA only needs to react for 15 min to obtain good analysis results. The proposed method has a wider detection range than commercial enzyme-linked immunosorbent assay (ELISA) kits (0.12-112.8 pmol/L > 0.5-40 pmol/L). In addition, results of G-17-AlphaLISA and ELISA had good correlation and agreement (ρ = 0.936). Importantly, the developed method may be more suitable for the large-scale screening of people at high risk for gastric cancer than traditional ELISA and provides a novel solution for other biomarkers that require accurate, highly sensitive, and high throughput detection.