De novo synthesis of a novel hapten and development of a monoclonal antibody-based immunoassay for the detection of dichlorvos and trichlorfon.

The absence of high-affinity antibodies has hindered the development of satisfactory immunoassays for dichlorvos (DDVP) and trichlorfon (TCP), two highly toxic organophosphorus pesticides. Herein, the de novo synthesis of a novel anti-DDVP hapten was introduced. Subsequently, a specific anti-DDVP monoclonal antibody (Mab) was produced with satisfying affinity to DDVP (IC50: 12.4 ng mL-1). This Mab was highly specific to DDVP, and TCP could readily convert into DDVP under mild alkaline conditions. Leveraging this insight, an indirect competitive ELISA was successfully developed for simultaneous detection of DDVP and TCP. The limit of detection in rice, cabbage and apple for DDVP /TCP was found to be 12.1/14.6 µg kg-1, 7.3/8.8 µg kg-1 and 6.9/8.3 µg kg-1, respectively. This study not only provides an effective strategy for producing a high-quality anti-DDVP Mab but also affords a reliable and cost-effective tool suitable for high-throughput detection of DDVP and TCP in food samples.

Quality of Life and Glucose Regulation in Pediatric Patients with Type 1 Diabetes: A Study in the Ningxia Hui Autonomous Region.

Objective: In this study, we aimed to evaluate the current status of the quality of life (QOL) of pediatric patients and plasma glucose concentration regulation in children with type 1 diabetes (T1DM) in the Ningxia Hui autonomous region. Methods: The study involved children with T1DM admitted to the General Hospital of Ningxia Medical University between October 2011 and October 2021. The children and their parents completed general information and quality of life (QOL) questionnaires. The regulation of plasma glucose concentration was assessed based on HbA1c levels, and plasma glucose and QOL-influencing components were investigated. Results: Among the 136 pediatric patients diagnosed with T1DM, the mean glycated hemoglobin (HbA1c) level was recorded at 8.7% (7.2%, 10.5%). A breakdown of the patient cohort revealed that 44 patients (32.4%) demonstrated good regulation of plasma glucose, 33 patients (24.3%) exhibited acceptable glycemic control, and 59 patients (43.3%) displayed poor regulation of plasma glucose. The control of plasma glucose in pediatric patients diagnosed with T1DM was affected by the duration of the disease, the patient's age, the frequency of daily plasma glucose measurements, the use of CGM, diabetic ketoacidosis (DKA), and the education level of the mother. The control of plasma glucose, dietary management, DKA, the ability to learn, and health education are interfering factors of quality of life in children diagnosed with T1DM. Effective control of plasma glucose may ensure the QOL in children with T1DM, and DKA was the risk factor for QOL. Conclusion: In Ningxia, the regulation of plasma glucose in pediatric and adolescent patients with T1DM remains suboptimal, leading to poor QOL. There is a pressing need to enhance glucose regulation and QOL through comprehensive strategies, which include reinforced dietary management, rigorous monitoring of plasma glucose levels, and heightened health education levels.

Antimicrobial carbon dots/pectin-based hydrogel for promoting healing processes in multidrug-resistant bacteria-infected wounds.

Multidrug-resistant (MDR) bacterial infections have become a significant threat to global healthcare systems. Here, we developed a highly efficient antimicrobial hydrogel using environmentally friendly garlic carbon dots, pectin, and acrylic acid. The hydrogel had a porous three-dimensional network structure, which endowed it with good mechanical properties and compression recovery performance. The hydrogel could adhere closely to skin tissues and had an equilibrium swelling ratio of 6.21, indicating its potential as a wound dressing. In particular, the bactericidal efficacy following 24-h contact against two MDR bacteria could exceed 99.99 %. When the hydrogel was applied to epidermal wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) on mice, a remarkable healing rate of 93.29 % was observed after 10 days. This was better than the effectiveness of the traditionally used antibiotic kanamycin, which resulted in a healing rate of 70.36 %. In vitro cytotoxicity testing and hemolysis assay demonstrated a high biocompatibility. This was further proved by the in vivo assay where no toxic side effects were observed on the heart, liver, spleen, lung, or kidney of mice. This eco-friendly and easy-to-prepare food-inspired hydrogel provides an idea for the rational use of food and food by-products as a wound dressing to control MDR bacterial infections.

Augmentation of scleral glycolysis promotes myopia through histone lactylation.

Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encoding glycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.

Effects of Nonmagnetic Zn2+ Ion and RE Ion Substitution on the Magnetic Properties of Functional Nanomaterials Co1-yZnyRExFe2-xO4 (RE = La, Sm, Gd) by Sol-Gel.

Magnetic Functional Nanomaterials Co1-yZnyRExFe2-xO4 (RE (rare-earth) = La,Sm,Gd) were prepared using the sol-gel combustion method. XRD characterization confirms that the ferrite samples we synthesized are single-phase cubic structures. The variation in the average crystalline size and lattice parameter is related to RE ion doping. The Mössbauer spectra of CoRExFe2-xO4 are two sets of magnetic six-wire peaks that indicate the ferrimagnetic behavior of the sample. The calcination temperature greatly influences the absorption area of Mössbauer for CoFe2O4, indicating that the calcination temperature affects the iron ion content at the octahedral B and tetrahedral A sites. Additionally, scanning electron microscopy measurements of the substituted specimens reveal that the ferrite powders are nanoparticles. With an increase in RE ions, the coercivity increases, and the saturation magnetization changes obviously. The XRD characterization of Co0.7Zn0.3LaxFe2-xO4 shows that the main crystalline phase of the sample is the cubic spinel structure phase, and there are fewer secondary crystalline phases. The lattice parameter tends to decrease with the substitution of La3+ ions. The average grain size decreased significantly with the increase in La content. From ferrimagnetic state transition to relaxation behavior, the hyperfine magnetic field decreases in La concentration by room temperature Mössbauer spectra. With the substitution of La3+ ions, both the saturation magnetization and coercivity of the samples were reduced, and the coercivity of all samples was lower.

A safety study on ultra­high or moderate static magnetic fields combined with platycodin D against lung cancer.

Due to the serious side effects of chemotherapy drugs against lung cancer, and the antitumor properties and high safety of magnetic fields, the present study combined moderate or ultra-high intensity statics magnetic fields (SMFs) with platycodin D (PD) to explore the antitumor efficiency and biosafety. The antitumor effects of PD with or without moderate and ultra-high SMFs on A549 cells bearing mice were compared. Mouse body weight, food/water intake, hematology routine, blood biochemistry, tumor weight and tissues hematoxylin and eosin (H&E) staining were examined. Behavior was measured using the elevated plus maze, open field and vital signs tests. The combined targets of PD and SMFs were detected using RNA-sequencing (RNA-seq). The results showed that the antitumor effect of 22 Tesla (T) SMF group was 3.6-fold higher compared with that of the 2 mg/kg PD group (tumor growth inhibition=10.08%), while the antitumor effect of 150 mT SMF was only 1.56-fold higher compared with that of PD. Although PD reduced the food intake, there was no significant difference in body weight, water intake or food consumption among PD and SMF groups. Behavioral results indicated that PD ameliorated dysphoria in mice, but SMFs reduced this effect. However, no significant abnormalities were found in routine blood, blood biochemistry test, H&E staining or organ index, except renal index which was reduced by PD with or without SMFs. RNA-sequencing (RNA-seq) demonstrated that SMFs and PD synergistically targeted the expression of genes associated with tumor growth, inflammation and neurological disease. The present study showed the antitumor efficacy and biosafety of moderate or ultra-high SMF combined with PD, which exhibited only few side effects in the treatment of lung cancer, thus supporting further research for the clinical application of magnetic fields.

Effect of Cd2+ Substitution on Structural-Magnetic and Dielectric Properties of Ni-Cu-Zn Spinel Ferrite Nanomaterials by Sol-Gel.

CdxNi0.5-xCu0.2Zn0.3Fe2O4 (0 ≤ x ≤ 0.50) ferrite with a spinel structure was prepared using the sol-gel self-propagation method. The effects of Cd2+ doping on the structure, morphology, dielectric, and magnetic properties of Ni-Cu-Zn ferrite were examined using XRD, SEM, EDX, FTIR, MPMS, and dielectric tests. The cubic spinel structure was verified by XRD and FTIR analyses. The crystallite size and particle size information of the samples were obtained with XRD and SEM analysis. The sample particle size belonged to a class of nanoscale materials with a particle size range of 1-100 nm. The minor difference between the grain size and particle size indicated that the sample nanoparticles were composed of numerous microcrystals. The EDX spectra indicated that the samples contained all stoichiometric elements. MPMS was used to measure the hysteresis lines of the samples. According to the hysteresis line, the saturation magnetization intensity (Ms), coercivity (Hc), and magnetic moment (µB) of the sample increased and then decreased with the increase in cadmium concentration. The magnetization strength (Ms) is between 4-67 emu/g, and the coercivity (Hc) is between 9-46 Oe. The curves of the real part of the dielectric constant (ε'), the imaginary part of the dielectric constant (ε″), and the loss factor (tanδ) with frequency were measured in the frequency range 100 Hz-100 kHz by means of an impedance analyzer. The complex modulus spectrum was analyzed to understand the dynamics of the conduction process.

Structural and Magnetic Properties of Perovskite Functional Nanomaterials La1-xRxFeO3 (R = Co, Al, Nd, Sm) Obtained Using Sol-Gel.

Perovskite is the largest mineral on earth and has a variety of excellent physical and chemical properties. La1-xRxFeO3 (R = Co, Al, Nd, Sm) were synthesized using the sol-gel method and analyzed by XRD, TG-DTA, and VSM. With the increase in the Co2+ doping content, the diffraction peak drifted in the direction of a larger angle. The grain size of La1-xRxFeO3(R = Co) is mainly concentrated between 50.7 and 133.5 nm. As the concentration of Co2+ increased, the magnetic loop area and magnetization increased. La1-xRxFeO3(R = Al) is an orthorhombic perovskite structure, the grain size decreased with the increase in Al3+ doping concentration, and the minimum crystallite is 17.9 nm. The magnetic loop area and magnetization increased with the increase in Al3+ ion concentration. The enclosed area of the M-H curve of the sample decreased, and the ferromagnetic order gradually weakened and tended to be antiferromagnetic, which may be due to the increase in sintering temperature, decrease in the iron oxide composition, and changes in the magnetic properties. Proper doping can improve the magnetization of La1-xRxFeO3(R = Nd), refine the particles, and obtain better magnetic performance. As the Nd3+ ion concentration increased, the magnetic properties of the samples increased. Ms of La0.85Co0.15FeO3 prepared by different calcination time increases with the increase in calcination time. As the Sm3+ ion concentration increased, the magnetic properties of the samples increased. Proper doping can improve the magnetization of La1-xRxFeO3(R = Sm), refine the particles, and generate better magnetic performance.

Development of an ultrasensitive sandwich immunoassay for detecting small molecule semicarbazide.

Ultrasensitive sandwich immunoassays for detecting the small molecule semicarbazide (SEM) were developed based on derivatization. Several SEM derivatizing agents were synthesized by linking o-nitrobenzaldehyde (NBA) and biotin with dihydroxyalkanes (different lengths), which were then used to evaluate the distance effect of two epitopes. Sandwich ELISA for SEM derivatives was developed using an anti-SEM-NBA antibody and horseradish peroxidase-labeled avidin or anti-biotin antibody as a secondary conjugate. The advantageous distances of the two epitopes under the double-antibody sandwich and antibody-avidin sandwich modes were ≥12 and ≥13 Å, respectively. Under the distances, the sensitivities of the sandwich ELISA were no lower than those of competitive ELISA. The obtained optimal EC50 values were 11.2 pg/mL (double-antibody sandwich with the epitope distance ≥16 Å) and 7.3 pg/mL (antibody-avidin sandwich with the epitope distance ≥17 Å). Compared with competitive ELISA, the developed method achieved a 30-fold improvement in sensitivity, with simpler aquatic product pretreatment.

Polysaccharides from Armillariella tabescens mycelia mitigate DSS-induced ulcerative colitis via modulating intestinal microbiota in mice.

Polysaccharides from Armillariella tabescens mycelia (AT) have a potent anti-inflammatory effect. Nevertheless, the impact of AT on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) has not yet been illustrated. This study aimed to explore AT's impact on experimental UC mice and investigate its underlying mechanisms. Mice were given DSS, 0.2 g/kg AT or 0.4 g/kg AT for seven days, and the symptoms of UC were observed. The serum and colon samples were harvested to analyze the biochemical indices and inflammasome-related proteins. The feces were collected to analyze short-chain fatty acids (SCFAs) and gut microbiota. The present study found that AT improved the symptoms of UC, colonic oxidative stress, and inflammation. AT treatment elevated SCFAs contents and colonic barrier function. Furthermore, AT improved microbial community structure through the selective enrichment of beneficial bacterial species. In conclusion, these results underlined that AT improved DSS-induced colitis and inhibited colonic inflammation via regulating the intestinal microbial community and enhancing the colonic mucosal barrier.

Magnetic Fields Affect Alcoholic Liver Disease by Liver Cell Oxidative Stress and Proliferation Regulation.

It is well known that alcohol consumption leads to substantially increased free radical levels and health risks, which lacks effective treatment besides alcohol abstinence. Here, we compared different static magnetic field (SMF) settings and found that a downward quasi-uniform SMF of ~0.1 to 0.2 T could effectively alleviate alcohol-induced liver damage and lipid accumulation and improve hepatic function. SMFs of two different directions can reduce the inflammation, reactive oxygen species levels, and oxidative stress in the liver, while the downward SMF had more obvious effects. Moreover, we found that the upward direction SMF of ~0.1 to 0.2 T could inhibit DNA synthesis and regeneration in hepatocytes, which caused detrimental effects on the lifespan of "heavy drinking" mice. In contrast, the downward SMF prolongs survival of "heavy drinking" mice. On one hand, our study shows that ~0.1 to 0.2 T moderate quasi-uniform SMFs with a downward direction have great promises to be developed into a physical method to reduce alcohol-induced liver damage; on the other hand, although the internationally recognized upper limit for SMF public exposure is 0.4 T, people should also pay extra attention to SMF strength, direction, and inhomogeneity that could generate harmful effects on specific severe pathological conditions.

Synthesis and characterization of pendant N,N-dimethylaminobenzaldehyde-functionalized chitosan Schiff base composite (CS@MABA) as a new sorbent for removal of Pb(II) ions from aqueous media.

In this work, new pendant N,N-dimethylaminobenzaldehyde-functionalized chitosan Schiff base composite (CS@MABA) was prepared from the simple and convenient condensation reaction between chitosan (CS) and N,N-dimethylaminobenzaldehyde (MABA) in ethanol-glacial acetic acid (1:1 v/v) and characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscope (SEM). The as-prepared composite CS@MABA was applied for the removal of Pb(II) ions, due to the presence of imine, hydroxyl and phenyl groups, and the effects of important parameters such as solution pH, contact time and sorbent dosage on the removal percentage and adsorption capacity were investigated and discussed. The optimum conditions were found to be at pH 5, adsorbent dosage of 0.1 g, Pb(II) concentration of 50 mg/L and contact time of 60 min. The maximum Pb(II) removal percentage was found to be 94.28 % with the high adsorption capacity of 165 mg/g. The adsorption capacity of CS@MABA is remain 87 % after 5 adsorption-desorption cycles. The adsorption kinetic and isotherm studies indicated that the Pb(II) removal by CS@MABA follows a pseudo-first order and Langmuir models, respectively. Compared to similar compounds, the synthesized CS@MABA composite has shown a relatively high yield for removing Pb(II) ions. According to these results, the CS@MABA suggested for the sorption of other heavy metals.

Early activation of Toll-like receptor-3 reduces the pathological progression of Alzheimer's disease in APP/PS1 mouse.

BACKGROUND: Toll-like receptor 3 (TLR3) plays an important role in the immune/inflammatory response in the nervous system and is a main pathological feature of Alzheimer's disease (AD). This study investigates the role of early activation of TLR3 in the pathophysiological process of AD. METHODS: In the experiment, the agonist of TLR3, Poly(I:C), was intraperitoneally injected into the APP/PS1 mouse model of AD and wild-type control mice starting from the age of 4 to 9 months. At the age of 14 months, behavioral tests were conducted. Western blot and immunohistochemistry staining were used to evaluate the level of amyloid ß-protein (Aß), the activation of inflammatory cells, and neuron loss. In addition, the levels of inflammatory cytokines were measured using a quantitative polymerase chain reaction. RESULTS: The results demonstrated that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction. Moreover, the early activation of TLR3 reduced Aß deposition, inhibited the activation of microglia and astrocytes, and decreased the transcription of pro-inflammatory factors in the hippocampus. CONCLUSIONS: The results indicated that the activation of TLR3 by Poly (I:C) in the early stage of development of AD in a mouse model attenuated neuron loss and improved neurobehavioral functions. The underlying mechanisms could be attributed to its role in Aß clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.

A bio-inspired nano-material recapitulating the composition, ultra-structure, and function of the glycosaminoglycan-rich extracellular matrix of nucleus pulposus.

The nucleus pulposus (NP) of intervertebral disc represents a soft gel consisting of glycosaminoglycans (GAGs)-rich extracellular matrix (ECM). Significant loss of GAGs and normal functions are the most prevalent changes in degenerated disc. Attempts targeted to incorporate GAGs into collagen fibrous matrices have been made but the efficiency is very low, and the resulting structures showed no similarity with native NP. Inspired by the characteristic composition and structures of the ECM of native NP, here, we hypothesize that by chemically modifying the collagen (Col) and hyaluronic acid (HA) and co-precipitating with GAGs, a bio-inspired nano-material recapitulating the composition, ultra-structure and function of the GAG-rich ECM will be fabricated. Compositionally, the bio-inspired nano-material namely Aminated Collagen-Aminated Hyaluronic Acid-GAG (aCol-aHA-GAG) shows a record high GAG/hydroxyproline ratio up to 39.1:1 in a controllable manner, out-performing that of the native NP. Ultra-structurally, the nano-material recapitulates the characteristic 'nano-beads' (25 nm) and 'bottle-brushes' (133 nm) features as those found in native NP. Functionally, the nano-material supports the viability and maintains the morphological and phenotypic markers of bovine NP cells, and shows comparable mechanical properties of native NP. This work contributes to the development of a compositionally, structurally, and functionally biomimetic nano-material for NP tissue engineering.

Carbon dots cooperatively modulating photocatalytic performance and surface charge of O-doped g-C3N4 for efficient water disinfection.

The emergence of widespread microbial contamination and drug-resistant bacteria in the water environment poses a severe threat to public health. Photocatalysis is considered an efficient, energy-saving, and cost-effective disinfection strategy for effectively removing microbial contamination from water bodies. In this paper, a metal-free O-doped g-C3N4/carbon dots (O-CN/CDs) nanosheet photocatalysts are prepared in coordination with various modification strategies, which results in a considerable improvement in photocatalytic disinfection activity compared to bulk g-C3N4 (B-CN). First, O-doping and morphology modulation are achieved simultaneously with hydrothermal treatment, which not only hinders the recombination of photogenerated hole-electron pairs, but also enables the exposure of more active centers. Subsequently, loading of CDs onto O-CN nanosheets by electrostatic self-assembly increases the production of photogenerated hole-electron pairs by expanding the visible light absorption region and promoted the separation of photogenerated carriers by trapping photogenerated electrons. Interestingly, the loading of CDs changes the charge on the surface of the composite photocatalyst from negative to positive, making it easier for the active species to come in contact with bacteria, and thus improving bacterial disinfection performance. Under visible light irradiation, the inactivation efficiency of optimized O-CN/CDs against methicillin-resistant Staphylococcus aureus (MRSA) is log(C/C0) = 4.08, approximately 9 times higher than that of B-CN. The main active species inactivating bacteria are superoxide anions radicals (•O2-) and photogenerated holes, and their attack causes damage to the membrane wall structure and leakage of intracellular components. Additionally, the feasibility of the as-prepared photocatalysts in water disinfection in real environments was confirmed by photocatalytic disinfection experiments in successive recovery cycles and in practical lake water.

The Effect of Long-Term Moderate Static Magnetic Field Exposure on Adult Female Mice.

Because of the high cost and safety of ultra-high magnetic resonance imaging (MRI), its application has certain limitations. Whereas 0.5−3 T MRI has been widely applied in hospitals, static magnetic fields (SMFs) have been shown to improve mice mental health and have anti-tumor potentials. Here, we compared the effects of the upward and downward 150 mT SMF groups with the sham group on C57BL/6J adult female mice. Locomotor and exploratory activity were also measured by behavioral tests, including the open field and elevated plus test. Additionally, physiology, pathology indicators and gut microbiota were examined. We found that 150 mT SMFs long-term exposure enhanced locomotive and exploratory activity of mice, especially the downward 150 mT SMF. Compared with the downward 150 mT SMF group, the movement speed and distance in the center area of the sham group were increased by 65.99% (p < 0.0001) and 68.58% (p = 0.0038), respectively. Moreover, compared to the sham group, downward 150 mT SMF increased the number of entrances to the center area by 67.0% (p = 0.0082) and time in the center area by 77.12% (p = 0.0054). Additionally, we observed that upward 150 mT SMF improved the number of follicles (~2.5 times, p = 0.0325) and uterine glands through increasing the total antioxidant capacity and reducing lipid peroxidation level in mice. Gut microbiome analysis showed that 150 mT SMFs long-term exposure improved the microbiota abundance (Clostridium, Bifidobacterium, Ralstonia and Yaniella) in the genus level, which may affect metabolism, anxiety and behavior in adult female mice. Our results demonstrated that 150 mT SMFs long-term exposure not only had good biosafety, but also improved athletic performance, emotion and the function of ovarian, uterine and gut microbiota abundance in adult female mice, which unraveled the potential of moderate long-term SMF exposure in clinical applications.

Advances in the study of liver microsomes in the in vitro metabolism and toxicity evaluation of foodborne contaminants.

Foodborne contaminants are closely related to anthropologic activities and represent an important food safety hazard. The study of metabolic transformation and toxic side effects of foodborne contaminants in the body is important for their safety assessment. Liver microsomes contain a variety of enzymes related to substance metabolism and biotransformation. An in vitro model simulating liver metabolic transformation is associated with a significant advantage in the study of the metabolic transformation mechanisms of contaminants. This review summarizes the recent progress in the application of liver microsomes in metabolic transformation and toxicity evaluation of various foodborne pollutants based on metabolic kinetics, molecular docking and enzyme inhibition studies. The purpose of this review is to distinguish the existing studies involving liver microsomes and provide strategies for their application in the future. Finally, the prospects and challenges of the liver microsomal model are discussed.

Soil microbial community assembly and stability are associated with potato (Solanum tuberosum L.) fitness under continuous cropping regime.

Continuous cropping obstacles caused by the over-cultivation of a single crop trigger soil degradation, yield reduction and the occurrence of plant disease. However, the relationships among stability, complexity and the assembly process of soil microbial community with continuous cropping obstacles remains unclear. In this study, molecular ecological networks analysis (MENs) and inter-domain ecological networks analysis (IDENs), and a new index named cohesion tools were used to calculate the stability and complexity of soil microbial communities from eight potato cultivars grown under a continuous cropping regime by using the high-throughput sequencing data. The results showed that the stability (i.e., robustness index) of the bacterial and fungal communities for cultivar ZS5 was significantly higher, and that the complexity (i.e., cohesion values) was also significantly higher in the bacterial, fungal and inter-domain communities (i.e., bacterial-fungal community) of cultivar ZS5 than other cultivars. Network analysis also revealed that Actinobacteria and Ascomycota were the dominant phyla within intra-domain networks of continuous cropping potato soil communities, while the phyla Proteobacteria and Ascomycota dominated the correlation of the bacterial-fungal network. Infer community assembly mechanism by phylogenetic-bin-based null model analysis (iCAMP) tools were used to calculate the soil bacterial and fungal communities' assembly processes of the eight potato cultivars under continuous cropping regime, and the results showed that the bacterial community was mainly dominated by deterministic processes (64.19% - 81.31%) while the fungal community was mainly dominated by stochastic processes (78.28% - 98.99%), indicating that the continuous-cropping regime mainly influenced the potato soil bacterial community assembly process. Moreover, cultivar ZS5 possessed a relatively lower homogeneous selection, and a higher TP, TN, AP and yield than other cultivars. Our results indicated that the soil microbial network stability and complexity, and community assemble might be associated with yield and soil properties, which would be helpful in the study for resistance to potato continuous cropping obstacles.

Epigallocatechin-3-gallate ameliorates renal endoplasmic reticulum stress-mediated inflammation in type 2 diabetic rats.

Epigallocatechin-3-gallate (EGCG), an essential polyphenolic constituent found in tea leaves, possesses various potent biological activities. This research was undertaken to investigate the impact of EGCG against endoplasmic reticulum (ER) stress-mediated inflammation and to clarify the underlying molecular mechanism in type 2 diabetic kidneys. The male rats were randomized into four groups: normal, diabetic, low-dose EGCG, and high-dose EGCG. In type 2 diabetic rats, hyperglycemia and hyperlipidemia noticeably caused renal structural damage and dysfunction and aggravated ER stress. Meanwhile, sustained ER stress activated the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and then upregulated the contents of inflammatory cytokines in the diabetic kidney. Following supplementation with 40 mg/kg and 80 mg/kg EGCG, hyperglycemia, hyperlipidemia, and renal histopathological alterations and dysfunction were noticeably ameliorated; renal ER stress, NLRP3 inflammasome, and inflammatory response were markedly repressed in the EGCG treatment groups. In summary, the current study highlighted the renoprotective effects of EGCG in type 2 diabetes and its mechanisms are mainly associated with the repression of ER stress-mediated NLRP3 inflammasome overactivation.

CD4+ T-cell epitope-based heterologous prime-boost vaccination potentiates anti-tumor immunity and PD-1/PD-L1 immunotherapy.

BACKGROUND: Antitumor therapeutic vaccines are generally based on antigenic epitopes presented by major histocompatibility complex (MHC-I) molecules to induce tumor-specific CD8+ T cells. Paradoxically, continuous T cell receptor (TCR) stimulation from tumor-derived CD8+ T-cell epitopes can drive the functional exhaustion of tumor-specific CD8+ T cells. Tumor-specific type-I helper CD4+ T (TH1) cells play an important role in the population maintenance and cytotoxic function of exhausted tumor-specific CD8+ T cells in the tumor microenvironment. Nonetheless, whether the vaccination strategy targeting MHC-II-restricted CD4+ T-cell epitopes to induce tumor-specific TH1 responses can confer effective antitumor immunity to restrain tumor growth is not well studied. Here, we developed a heterologous prime-boost vaccination strategy to effectively induce tumor-specific TH1 cells and evaluated its antitumor efficacy and its capacity to potentiate PD-1/PD-L1 immunotherapy. METHODS: Listeria monocytogenes vector and influenza A virus (PR8 strain) vector stably expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein-specific I-Ab-restricted CD4+ T cell epitope (GP61-80) or ovalbumin-specific CD4+ T cell epitope (OVA323-339) were constructed and evaluated their efficacy against mouse models of melanoma and colorectal adenocarcinoma expressing lymphocytic choriomeningitis virus glycoprotein and ovalbumin. The impact of CD4+ T cell epitope-based heterologous prime-boost vaccination was detected by flow-cytometer, single-cell RNA sequencing and single-cell TCR sequencing. RESULTS: CD4+ T cell epitope-based heterologous prime-boost vaccination efficiently suppressed both mouse melanoma and colorectal adenocarcinoma. This vaccination primarily induced tumor-specific TH1 response, which in turn enhanced the expansion, effector function and clonal breadth of tumor-specific CD8+ T cells. Furthermore, this vaccination strategy synergized PD-L1 blockade mediated tumor suppression. Notably, prime-boost vaccination extended the duration of PD-L1 blockade induced antitumor effects by preventing the re-exhaustion of tumor-specific CD8+ T cells. CONCLUSION: CD4+ T cell epitope-based heterologous prime-boost vaccination elicited potent both tumor-specific TH1 and CTL response, leading to the efficient tumor control. This strategy can also potentiate PD-1/PD-L1 immune checkpoint blockade (ICB) against cancer.