Tebuconazole promotes spread of a multidrug-resistant plasmid into soil bacteria to form new resistant bacterial strains.

The development of antibiotic resistance threatens human and environmental health. Non-antibiotic stressors, including fungicides, may contribute to the spread of antibiotic resistance genes (ARGs). We determined the promoting effects of tebuconazole on ARG dissemination using a donor, Escherichia coli MG1655, containing a multidrug-resistant fluorescent plasmid (RP4) and a recipient (E. coli HB101). The donor was then incorporated into the soil to test whether tebuconazole could accelerate the spread of RP4 into indigenous bacteria. Tebuconazole promoted the transfer of the RP4 plasmid from the donor into the recipient via overproduction of reactive oxygen species (ROS), enhancement of cell membrane permeability and regulation of related genes. The dissemination of the RP4 plasmid from the donor to soil bacteria was significantly enhanced by tebuconazole. RP4 plasmid could be propagated into more genera of bacteria in tebuconazole-contaminated soil as the exposure time increased. These findings demonstrate that the fungicide tebuconazole promotes the spread of the RP4 plasmid into indigenous soil bacteria, revealing the potential risk of tebuconazole residues enhancing the dissemination of ARGs in soil environments.

Astrocyte Activation in the ACC Contributes to Comorbid Anxiety in Chronic Inflammatory Pain and Involves in The Excitation-Inhibition Imbalance.

Neurons within the anterior cingulate cortex (ACC) orchestrate the co-occurrence of chronic pain and anxiety. The ACC hyperactivity plays a crucial role in the emotional impact of neuropathic pain. Astrocyte-mediated neuroinflammatory is responsible for regulating the balance between excitation-inhibition (E/I) in the brain. However, there is limited understanding of the possible contributions of astrocytes in the ACC to comorbidity of anxiety and chronic inflammatory pain. This paper aims to investigate the possible contribution of astrocytes in the ACC to the comorbidity between anxiety and chronic inflammatory pain, as well as their involvement in the E/I imbalance of pyramidal cells. Our results show that CFA rats displayed allodynia and anxiety-like behaviors. The E/I balance in the ACC shifts to excitement in comorbidity of chronic pain and anxiety by western blotting, and electrophysiological recording. Result of RNA-Seq also indicated that E/I imbalance and neuroinflammation of ACC were involved in pain-anxiety comorbidity. Then, positive cells of GFAP but not Iba1 in the contralateral ACC were increased; the mRNA expression of GFAP and its activation-related proinflammatory cytokines (TNF-α, IL-6, and IL-1ß) in the contralateral ACC were also elevated. Furthermore, specific chemogenic inhibition of ACC astrocytes reversed comorbid pain and anxiety and suppressed high ACC excitability. Our data suggest that astrocytes participate in comorbid pain and anxiety and excitation-inhibition imbalance in ACC. Inhibition astrocyte activation can reduce anxiety related to pain and restore the imbalance in the ACC. These findings shed light on the involvement of astrocytes in comorbid conditions, offering valuable insights into a potential therapeutic approach for the co-occurrence of chronic pain and anxiety.

Mechanisms Underlying the Overlooked Chiral Fungicide-Driven Enantioselective Proliferation of Antibiotic Resistance in Earthworm Intestinal Microbiome.

From a "One Health" perspective, the global threat of antibiotic resistance genes (ARGs) is associated with modern agriculture practices including agrochemicals application. Chiral fungicides account for a considerable proportion of wildly used agrochemicals; however, whether and how their enantiomers lead to differential proliferation of antibiotic resistance in agricultural environments remain overlooked. Focused on the soil-earthworm ecosystem, we for the first time deciphered the mechanisms underlying the enantioselective proliferation of antibiotic resistance driven by the enantiomers of a typical chiral fungicide mandipropamid (i.e., R-MDP and S-MDP) utilizing a multiomic approach. Time-series metagenomic analysis revealed that R-MDP led to a significant enhancement of ARGs with potential mobility (particularly the plasmid-borne ARGs) in the earthworm intestinal microbiome. We further demonstrated that R-MDP induced a concentration-dependent facilitation of plasmid-mediated ARG transfer among microbes. In addition, transcriptomic analysis with verification identified the key aspects involved, where R-MDP enhanced cell membrane permeability, transfer ability, biofilm formation and quorum sensing, rebalanced energy production, and decreased cell mobility versus S-MDP. Overall, the findings provide novel insights into the enantioselective disruption of microbiome and resistome in earthworm gut by chiral fungicides and offer significant contributions to the comprehensive risk assessment of chiral agrochemicals in agroecosystems.

A novel bidirectional regulation mechanism of mancozeb on the dissemination of antibiotic resistance.

The high abundance of antibiotic resistance genes (ARGs) in the fungicide residual environment, posing a threat to the environment and human health, raises the question of whether and how fungicide promotes the prevalence and dissemination of antibiotic resistance. Here, we reported a novel mechanism underlying bidirectional regulation of a typical heavy-metal-containing fungicide mancozeb on the horizontal transfer of ARGs. Our findings revealed that mancozeb exposure significantly exerted oxidative and osmotic stress on the microbes and facilitated plasmid-mediated ARGs transfer, but its metallic portions (Mn and Zn) were potentially utilized as essential ions by microbes for metalating enzymes to deal with cellular stress and thus reduce the transfer. The results of transcriptome analysis with RT-qPCR confirmed that the expression levels of cellular stress responses and conjugation related genes were drastically altered. It can be concluded mancozeb bidirectionally regulated the ARGs dissemination which may be attributed to the diverse effects on the microbes by its different portions. This novel mechanism provides an updated understanding of neglected fungicide-triggered ARGs dissemination and crucial insight for comprehensive risk assessment of fungicides.

High detectivity solar blind photodetector based on mechanical exfoliated hexagonal boron nitride films.

As an ultra-wide bandgap semiconductor, hexagonal boron nitride (h-BN) has drawn great attention in solar-blind photodetection owing to its wide bandgap and high thermal conductivity. In this work, a metal-semiconductor-metal structural two-dimensional h-BN photodetector was fabricated by using mechanically exfoliated h-BN flakes. The device achieved an ultra-low dark current (16.4 fA), high rejection ratio (R205nm/R280nm= 235) and high detectivity up to 1.28 × 1011Jones at room temperature. Moreover, due to the wide bandgap and high thermal conductivity, the h-BN photodetector showed good thermal stability up to 300 °C, which is hard to realize for common semiconductor materials. The high detectivity and thermal stability of h-BN photodetector in this work showed the potential applications of h-BN photodetectors working in solar-blind region at high temperature.

Investigation of Histamine Removal by Electrodialysis from the Fermented Fish Sauce and Its Effects on the Flavor.

Histamine is one of the most concerned safety indicators in fish sauce. Considering its charge property, electrodialysis (ED) was used to control the histamine in fish sauce, and studies were focused on three operating parameters: input current, pH, and flow velocity. A Box-Behnken design and response surface methodology was adopted to derive a statistical model, which indicated that 5.1 A input current, pH 3.8, and 40 L∙h-1 flow velocity were optimal operation conditions. Under this condition, the histamine removal rate reached 53.41% and the histamine content met the allowable histamine limit of below 400 mg·kg-1 in fish sauce, while the amino nitrogen (ANN) loss rate was only 15.46%. In addition, amino acids and volatile compounds changed differently during ED. As a result, with decreased histamine, the fish sauce after ED was also less salty and less fishy. The study first explored utilizing ED to remove histamine from fish sauce, which has positive implications for promoting the safety of aquatic products.

Deposition and dissipation of difenoconazole in pepper and soil and its reduced application to control pepper anthracnose.

The initial deposition amount, dissipation dynamics, retention rate, and field control efficacy of difenoconazole in pepper-soil system were studied with different application dosages, planting regions and patterns. The initial deposition amount of difenoconazole under the same application dosage showed the following order: fruits < cultivated soils < lower stems < upper stems < lower leaves < upper leaves, open field < greenhouse, and Changjiang < Cixi < Hefei < Langfang, respectively, which increased with increasing application dosage. The dissipation rates in leaves, stems, fruits and cultivated soils exhibited an initially fast and then slow trend, while the retention rates displayed a tendency of first increasing and then stabilizing with increasing application dosages. After 7 d of difenoconazole application, the retention rates at five concentrations were 10.3%- 39.1%, and the field efficacy mostly reached the minimum effective dose. These results suggested that difenoconazole could be reduced by 25% based on the minimum recommended dose meeting the requirements of field control efficacy for controlling pepper anthracnose.

Risk factors analysis and risk assessment model construction of systemic lupus erythematosus patients with infection.

OBJECTIVE: To analyze the characteristics of peripheral blood lymphocyte subsets in systemic lupus erythematosus (SLE) patients with infection and non-infection group. Explore the risk factors of infection in SLE patients and establish a risk matrix model to predict the occurrence of co-infection. METHODS: total of 333 SLE patients without infection, 163 patients suffering from infection, and 132 healthy controls (HCs) were recruited. General clinical data and disease activity indicators were collected. The levels of total T, B, CD4+T, CD8+T, NK, Th1, Th2, Th17, and Treg cells in peripheral blood of HCs, SLE patients (including infected and non-infected group) were analyzed by flow cytometry. The risk assessment model was constructed, and the receiver operating characteristic curve was drawn. 39 SLE patients with infection and 20 patients without infection were randomly selected to evaluate the predictive power of the regression model. RESULTS: The levels of T, B, CD4+T, CD8+T, and NK cells in the infected patients were significantly decreased when compared with that of both non-infected patients and HCs (p < .05). The non-infected patients had a higher level of Th17 than that of HCs (p < . 05), but the absolute numbers of Th17 in infected patients was the lowest among the three groups (p < .001). The number of Treg cells in SLE patients was significantly lower than that of HCs (p < .01), and the infected patients had the fewest Treg cells among all these groups (p < . 05). A risk assessment model for SLE with infection was established, p = 1/(1-e-y), Y = 1.763-0.004 × Absolute number of CD4 + T cells-0.005 × Absolute number of NK cells -0.005 × Platelet count(×1012/L) + 1.033 × Absolute number of lymphocytes (×109/L) + 0.023 × C-reactive protein (mg/dL), whose predictive sensitivity is 77.5%, and specificity is 78.3%. CONCLUSION: The new risk assessment model exhibits good predictive ability to assess co-infection risk in SLE patients. T cells, NK cells, and CD4 + T cells along with other parameters help in differentiating Lupus with infection from Lupus alone.

Low-dose IL-2 therapy limits the reduction in absolute numbers of peripheral lymphocytes in systemic lupus erythematosus patients with infection.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by disturbed cellular and humoral immune responses. Dysregulations of immune system and immunosuppressive medications predispose SLE patients to infection. This study aims to investigate the alterations and absolute concentrations of lymphocyte subpopulations in SLE patients with different infection and their responses of low-dose IL-2 therapy. METHODS: A total of 333 patients with SLE without recent infection, 162 patients suffering infection, and age and sex-matched 132 healthy controls (HCs) were recruited. Of them, 54 SLE patients (including 41 non-infected group and 13 infected group) received a 5-day course of low-dose IL-2 administration at a dose of 0.5 million IU per day. Lymphocyte subpopulations were analyzed by flow cytometry. RESULTS: Patients with SLE had lower levels of lymphocyte subpopulations in peripheral blood such as T, B, NK, CD4 + T, CD8+ T, Th1, Th2, Th17, and Treg cells, and the reduction in these cells was more obvious in patients with infection (p <.05 to p <.01). Low-dose IL-2 effectively expanded T (p <.001), B (p <.001), CD4 + T (p <.01), CD8 + T (p <.001), Th1 (p <.01), Th17 (p <.1), and Treg cells (p <.01) of SLE patients, these cells were comparable to that of HCs after the IL-2 treatment. CONCLUSIONS: Patients with SLE had insufficiency of circulating lymphocyte subsets. This phenomenon was more obverse in those accompanying infection, suggesting the low concentration of lymphocytes may be used as indicators of high infection risk in SLE patients. Low-dose IL-2 induced expansion of Treg cells and NK cells, which may contribute to the restoration of immune homeostasis in SLE patients.

Analysis of dietary quality of preschool left behind children by using the revised Chinese diet balance index / 中国学校卫生

Objective@#To evaluate the dietary quality by adjusted diet balance index (DBI_16) of preschool left behind children in Anhui Province, and to provide a reference for rapidly and accurately evaluating their nutrition condition.@*Methods@#During September to December of 2018, selected 306 left behind children and 598 non left behind children aged 3-6 years old of Anhui Province in total. Four scoring methods (TS total score, LBS Low Bound Score, HBS High Bound Score, DQD Diet Quality Distance) were used to evaluate the dietary quality by Diet Balance Index Revision (DBI_16), and scores were compared to reflect the diet quality of preschool children in LBC group and NLBC group.@*Results@#The score of TS (-18.2, -16.1) in LBC group was lower than that of NLBC group, the scores of LBS(24.8, 23.1), HBS (7.9, 6.4) and DQD (35.9, 34.4) in LBC group were higher than that of NLBC group( Z =-46.02, 12.45, 4.14, 4.78, P <0.05). The daily intake of vegetables, fruits, animal food, milk, soybean and drinking water were obviously under the RNI, the dietary intake scores of milk(-4.1, -2.7), animal food (-2.2, -0.8) and food species (-7.4, -6.2) in LBC group were higher than that in NLBC group( Z =-26.42, 13.51, -6.59, P <0.01). About 44.1% of the preschool LBC were in moderate or severe deficit of food intake, 66.0% of the LBC were in the higher level of dietary imbalance, the LBC group s excessive and imbalance problem were of significant differences than those in the NLBC group ( χ 2=15.79, 11.51, P <0.05).@*Conclusion@#The dietary quality of preschool children in Anhui Province should be improved, the main diet problem was the dietary imbalance, which was related to deficiency in nutrients intake. The scores of DBI_16 in LBC group were significant different with those in NLBC group, it is necessary to take specific intervention to increase the intake of milk, eggs and fruits among preschool children.

Anxiolytic effect of GABAergic neurons in the anterior cingulate cortex in a rat model of chronic inflammatory pain.

Chronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABAAR agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABAAR antagonist picrotoxin induced anxiety-like behaviors but had no effect on pain in normal rats. Notably, chemogenetic activation of GABAergic neurons in the ACC alleviated chronic inflammatory pain and pain-induced anxiety-like behaviors, enhanced inhibitory presynaptic transmission, and reduced the excitability of ACC PNs. Chemogenetic inhibition of GABAergic neurons in the ACC led to pain-induced anxiety-like behaviors, reduced inhibitory presynaptic transmission, and enhanced the excitability of ACC PNs but had no effect on pain in normal rats. We demonstrate that the GABAergic system mediates a reduction in inhibitory presynaptic transmission in the ACC, which leads to enhanced excitability of pyramidal neurons in the ACC and is associated with chronic inflammatory pain-related anxiety.

Role of GABAAR in the Transition From Acute to Chronic Pain and the Analgesic Effect of Electroacupuncture on Hyperalgesic Priming Model Rats.

Chronic pain is a costly health problem that impairs health-related quality of life when not effectively treated. Regulating the transition from acute to chronic pain is a new therapeutic strategy for chronic pain that presents a major clinical challenge. The underlying mechanisms of pain transition are not entirely understood, and strategies for preventing this transition are lacking. Here, a hyperalgesic priming model was used to study the potential mechanism by which γ-aminobutyric acid receptor type A (GABAAR) in the dorsal root ganglion (DRG) contributes to pain transition. Furthermore, electroacupuncture (EA), a modern method of acupuncture, was administered to regulate pain transition, and the mechanism underlying EA's regulatory effect was investigated. Hyperalgesic priming was induced by intraplanar injection of carrageenan (Car)/prostaglandin E2 (PGE2). The decrease in mechanical withdrawal threshold (MWT) induced by PGE2 returned to baseline 4 h after injection in NS + PGE2 group, and still persisted 24 h after injection in Car + PGE2 group. Lower expression of GABAAR in the lumbar DRG was observed in the model rats. Furthermore, activating or blocking GABAAR could reversed the long-lasting hyperalgesia induced by Car/PGE2 injection or produced a persistent hyperalgesia. In addition, GABAAR may be involved in Protein Kinase C epsilon (PKCε) activation in the DRG, a mark molecular of pain transition. EA considerably increased the mechanical pain thresholds of hyperalgesic priming model mammals in both the acute and chronic phases. Furthermore, EA upregulated the expression of GABAAR and inhibited the activation of PKCε in the DRG. In addition, peripheral administration of picrotoxin blocked the analgesic effect of EA on the model rats and abolished the regulatory effect of EA on PKCε activation. These findings suggested that GABAAR plays a key role in both the transition from acute to chronic pain and the analgesic effect of EA on hyperalgesic priming.

Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex.

Chronic inflammatory pain is a common clinical disease that tends to be associated with negative emotions such as anxiety and depression. The anterior cingulate cortex (ACC) is involved in pain and pain-related anxiety, and γ-aminobutyric acid (GABA)-ergic interneurons play an important role in chronic pain and anxiety. Electroacupuncture (EA) has good analgesic and antianxiety effect, but the underlying mechanisms have not yet been fully elucidated. In this study, we established a chronic inflammatory pain model and observed that this model induced anxiety-like behaviors and decreased the numbers of parvalbumin (PV) and somatostatin (SOM) positive cells. Activation of PV but not SOM interneurons by chemogenetic techniques alleviated anxiety-like behaviors and pain sensation. EA treatment improved pain sensation, anxiety-like behaviors and increased the number of PV- positive cells in the ACC, but did not affect on the number of SOM-positive cells in the ACC. Moreover, specific inhibition of PV interneurons by chemogenetic methods reversed the analgesic and antianxiety effects of EA. These results suggest that EA ameliorates chronic inflammatory pain and pain-related anxiety by upregulating PV but not SOM interneurons in the ACC.

Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis.

BACKGROUND: Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy. METHODS: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan-Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. RESULTS: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients. CONCLUSIONS: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

An in vivo method for diversifying the functions of therapeutic antibodies.

V(D)J recombination generates mature B cells that express huge repertoires of primary antibodies as diverse immunoglobulin (Ig) heavy chain (IgH) and light chain (IgL) of their B cell antigen receptors (BCRs). Cognate antigen binding to BCR variable region domains activates B cells into the germinal center (GC) reaction in which somatic hypermutation (SHM) modifies primary variable region-encoding sequences, with subsequent selection for mutations that improve antigen-binding affinity, ultimately leading to antibody affinity maturation. Based on these principles, we developed a humanized mouse model approach to diversify an anti-PD1 therapeutic antibody and allow isolation of variants with novel properties. In this approach, component Ig gene segments of the anti-PD1 antibody underwent de novo V(D)J recombination to diversify the anti-PD1 antibody in the primary antibody repertoire in the mouse models. Immunization of these mouse models further modified the anti-PD1 antibodies through SHM. Known anti-PD1 antibodies block interaction of PD1 with its ligands to alleviate PD1-mediated T cell suppression, thereby boosting antitumor T cell responses. By diversifying one such anti-PD1 antibody, we derived many anti-PD1 antibodies, including anti-PD1 antibodies with the opposite activity of enhancing PD1/ligand interaction. Such antibodies theoretically might suppress deleterious T cell activities in autoimmune diseases. The approach we describe should be generally applicable for diversifying other therapeutic antibodies.

Prevalence of iron deficiency anemia and the association with dietary nutrition factors of preschool children in rural Anhui Province / 中国学校卫生

Objective@#To evaluate the dietary quality for preschool children by diet balance index(DBI_C), and to provide an empirical reference for scientific guidance for a reasonable diet and controlling and preventing iron deficiency anemia(IDA).@*Methods@#During September to December of 2018, 306 left behind children and 598 non left behind children aged 3-6 years old of Anhui Province were selected. Four scoring methods (TS Total Score, LBS Low Bound Score, HBS High Bound Score, DQD Diet Quality Distance) were used to evaluate the dietary quality by DBI_C, and multivariate Logistic regression was used to assess the relationship between DBI_C and IDA.@*Results@#The anemia prevalence (AP) was 13.3% among the 3-6 year old children in Anhui rural area, whereas the left behind children (LBC) was 16.7% and the non left behind children was 10.9%, and there was statistical significance of the differences ( χ 2=8.8, P <0.05). There were significant differences of TS[-18.3(25.2，-12.7)，-15.2(-19.8，-8.6)], LBS[25.4(18.3，32.5)，22.7(16.5，30.6)] and DQD[36.8(23.9，43.4)，34.1(27.5，41.0)] in DBI_C scores between anemia group and nonanemia group ( P <0.05). There were significant differences of milk and beans [-5.9(-10.7，-0.4)，-5.0(-8.7，0.2)], animal food [-2.4(-5.6，0.8)，-0.6(3.5，1.9)], food species [-7.5(-9.1，-4.8)，-6.3(-8.0，-2.9)] in food intake scores between anemia group and non anemia group ( P <0.05). Left behind children ( OR =1.27, 95% CI =1.15-1.49) had higher proportions of getting anemia. Meat consumption >3 times per week ( OR =0.81, 95% CI =0.68-0.94) and ≥two types of fresh vegetable consumption every day ( OR =0.84, 95% CI =0.73-0.95) were associated with lower rate of anemia( P <0.05).@*Conclusion@#The AP was relatively high in 3-6 year old children in Anhui rural area, especially in those LBC. Anemia should be reduced by improving the caregivers dietary literacy, increasing intakes of animal foods and fresh vegetables.

The numbers of peripheral regulatory T cells are reduced in patients with psoriatic arthritis and are restored by low-dose interleukin-2.

BACKGROUND: Although regulatory T cells (Tregs) play crucial roles in the maintenance of immune hemostasis, the numbers of peripheral Tregs in patients with psoriatic arthritis (PsA) remain unclear. We measured these numbers and the efficacy and safety of low-dose interleukin-2 (IL-2) therapy. METHODS: We recruited 95 PsA patients, of whom 22 received subcutaneous low-dose IL-2 [0.5 million international units (MIU) per day for 5 days] combined with conventional therapies. The absolute numbers of cells in peripheral CD4+ T cell subsets were measured via modified flow cytometry. Clinical and laboratory indicators were compared before and after treatment. RESULTS: PsA patients had lower peripheral Treg numbers than healthy controls (p < 0.01), correlating significantly and negatively with the levels of disease indicators (p < 0.05). Although low-dose IL-2 significantly increased the Th17 and Treg numbers in PsA patients compared with the baseline values, the Treg numbers rose much more rapidly than those of Th17 cells, re-balancing the Th17 and Treg proportions. Low-dose IL-2 combination therapy rapidly reduced PsA disease activities as indicated by the DAS28 instrument, thus the number of tender joints, visual analog scale pain, physician global assessment, the dermatology life quality index score, and the health assessment questionnaire score (all p < 0.05). CONCLUSION: PsA patients exhibited low Treg numbers. Low-dose IL-2 combination treatment increased these numbers and relieved disease activity without any apparent side effects. Additional studies are required to explore the long-term immunoregulatory utility of IL-2 treatment.

Reticulocalbin-1 knockdown increases the sensitivity of cells to Adriamycin in nasopharyngeal carcinoma and promotes endoplasmic reticulum stress-induced cell apoptosis.

Nasopharyngeal carcinoma (NPC) mainly appears in southeastern Asian countries, including China. Adriamycin (ADM), a type of antitumor drug, is widely applied in treatments against various cancers. Nevertheless, cancer cells will eventually develop drug resistance to ADM. The present study aims to explore the potential role of reticulocalbin-1 (RCN1) in NPC cells resistance to ADM. Microarray-based analysis was used to screen NPC-related genes, with RCN1 acquired for this current study. RCN1 expression in NPC tissues and cells was determined. The biological function of RCN1 on NPC cell apoptosis was evaluated via gain- and loss-of-function experiments in 5-8 F/ADM and 5-8 F cells by delivering si-RCN1 and RCN1-vector. The function of endoplasmic reticulum (ER) stress on cell apoptosis was measured with the involvement of the PERK-CHOP signaling pathway. Furthermore, tumor formation in nude mice was performed to evaluate the survival condition and RCN1 effects in vivo. RCN1 was highly expressed in NPC tissues and cell lines. The increased expression of ER-related proteins ATF4, CHOP, and the extents of IRE1 and PERK phosphorylation were observed. RCN1 knockdown was found to reduce resistance of NPC cells/tissues to ADM while activating ER stress through the activated PERK-CHOP signaling pathway, which further promoted NPC cell apoptosis. These in vitro findings were detected in vivo on tumor formation in nude mice. In conclusion, the present study provides evidence that RCN1 knockdown stimulates ADM sensitivity in NPC by promoting ER stress-induced cell apoptosis, highlighting a theoretical basis for NPC treatment.

[Potential interaction effect on obesity between sleep duration and dietary patterns in preschool children in Bengbu City in 2018-2019].

OBJECTIVE: To examine the interaction effect between sleep duration and dietary patterns on obesity, in order to explore the possible risk factors for preschool children's obesity. METHODS: During September of 2018 to March of 2019(1148 boys and 981 girls, 1199 living in urban and 930 living in rural, 756 only child and 1373 not only child), a total of 2129 preschool children used two-stage cluster sampling method from 22 kindergartens aged 3-6 years old were investigated. Social-demographic information(included sex, age, only child or not, left-behind children or not, economic status of family, parents 'cultural level and caregivers' information), sleep duration and dietary intake were collected through "Sleep Duration and Physical Development Questionnaire(SDPDQ) of children aged 3-6 years old in Bengbu city". Factor analysis was applied to determine major dietary patterns, unconditional Logistic regression was used to analyze the multiplication interaction effect between sleep duration and dietary patterns on obesity. RESULTS: Four dietary patterns-"traditional", "animal", "calcium" and "snack" were identified in our study by principal component analysis. The factor contribution rate of the four dietary patterns was 16. 568%, 11. 462%, 7. 317% and 4. 562%, respectively, the total variance was 39. 909%. Among the preschool children, the prevalence of overweight and obesity were 18. 0%(n=383) and 10. 5%(n=223), respectively. After controlling the confounding factors, the shorter sleep duration(OR=1. 25, 95%CI 1. 07-1. 72), scores in the top quintile of "animal" pattern(OR=1. 32, 95%CI 1. 15-1. 54) and "snack" pattern(OR=1. 46, 95%CI 1. 16-1. 78) showed greater odds with the prevalence of overweight/obesity among preschool children. Both multiplication and additive interactions were observed between levels of low sleep duration and animal dietary pattern with overweight/obesity(OR=1. 23, 95%CI 1. 16-1. 32). Multiplication interaction was observed between lower sleep time and the snack dietary pattern(OR=1. 16, 95%CI 1. 09-1. 24), with RERI, AP and SI was 0. 38, 0. 20 and 1. 24, respectively. However, neither multiplication interaction or additive interaction was noticed between sleep duration and the traditional dietary pattern, the calcium dietary pattern with OR=0. 76(95%CI 0. 51-1. 11) vs. OR=1. 04(95%CI 0. 65-1. 73), respectively. CONCLUSION: Levels of low sleep duration presented a risk factor for overweight/obesity in preschool children. Both multiplication and additive interactions were observed between low sleep time and the animal dietary pattern. Multiplication interaction was noticed between children's sleep duration and the snack dietary pattern.