Optimizing growth and antioxidant function in heat-stressed broilers with vitamin C and betaine supplementation.

This study investigates the potential of vitamin C (VC) and/or betaine (Bet) to enhance growth performance, regulate serum metabolism, and bolster antioxidant function aiming to mitigate the impact of heat stress (HS) on broilers. Two hundred Ross 308 broilers at 28 days of age were randomly assigned to five groups. The control group, housed at 24 ± 1℃, was fed a basal diet. High-temperature treatment groups, housed at 32 ± 1℃, received a basal diet with 0 (HS group), 250 mg/kg VC (HSVC group), 1000 mg/kg Bet (HSBe group), and 250 mg/kg VC + 1000 mg/kg Bet (HSVCBe group). On day 42, assessments were made on growth performance, muscle quality, serum biochemistry, and antioxidant function. Results revealed that HS significantly lowered (P < 0.05) average daily feed intake (ADFI), the degree of redness (a*) in muscles, and serum total superoxide dismutase (T-SOD) level. It also reduced (P < 0.01) average daily gain (ADG), and serum total antioxidant capacity (T-AOC) level, while increasing (P < 0.05) shear force, serum direct bilirubin (D-BIL), uric acid (UA), and malondialdehyde (MDA) levels compared with the control group. Dietary supplementation of VC and Bet, either alone or in combination, significantly decreased shear force and serum UA level, while increasing ADG and serum T-AOC, T-SOD level compared with the HS group (P < 0.05). In conclusion, the addition of VC and/or Bet to the diet proves effective in enhancing the growth performance of HS-exposed broilers through the positive regulation of serum chemical metabolism and the alleviation of oxidative damage.

Effects of Bacillus subtilis and Lactobacillus on growth performance, serum biochemistry, nutrient apparent digestibility, and cecum flora in heat-stressed broilers.

This study investigates the effect of dietary Bacillus subtilis and Lactobacillus on the growth performance, serum biochemistry, nutrient apparent digestibility, and cecum flora of broilers under heat stress (HS) and provides a theoretical basis for the application of probiotic additives to alleviate the stress of poultry under HS. A total of 200 Cobb broilers were randomly assigned to four replicates of 10 broilers in each of the five groups. The growth performance, serum biochemistry, nutrient apparent digestibility, and cecum flora of broilers were detected on the 28th, 35th, and 42nd days, respectively. Results revealed that HS can affect the growth performance and serum biochemical indexes of broilers, lowered the number of intestinal bifidobacteria and Lactobacillus, and increase the number of Escherichia coli in comparsion to the CON group. Compared with the HS group, the ADFI of HS broilers in the BS group and the combined group significantly increased (P < 0.05) at 22-28 days of age, and the serum calcium and phosphorus increased (P < 0.05) significantly at 42 days of age. Meanwhile, the number of Lactobacillus in the BS group and LAB group increased significantly at 42 days of age (P < 0.05). The number of Escherichia coli in the LAB group and combination group decreased significantly at 35 days of age (P < 0.01). The present study revealed that the addition of Bacillus subtilis or Lactobacillus to diets increased ADFI, increased probiotic counts, and lowered Escherichia coli counts in HS broilers, while probiotics alone work well.

Two Novel Diterpenoid Alkaloids from Aconitum Pendulum.

Two previously uncharacterized compounds, an aconitine-type C19-diterpenoid alkaloid (1) and a napelline-type diterpenoid alkaloid C20-diterpenoid alkaloid (2), as well as ten known compounds (3-12), were isolated from Aconitum pendulum. Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction analysis. The anti-insecticidal activities of these compounds were evaluated by contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 9 showed moderate contact toxicity, with LC50 values of 0.86±0.09, 0.95±0.23, and 0.89±0.19 mg/mL, respectively. This study highlights the potential use of diterpenoid alkaloids as natural plant-derived pesticides for the management of plant pests.

Betaine ameliorates heat stress-induced apoptosis by affecting oxidative and endoplasmic reticulum stress in mouse Leydig cells.

In order to explore the potential protective role of betaine in heat stress (HS)-elicited apoptosis in mouse Leydig cells (mLCs). Betaine at 16 mm exerted a greater inhibitory effect on HS-induced viability attenuation of cells, which also significantly suppressed the heat shock protein 70 level in HS-treated cells. Furthermore, betaine ameliorated certain negative effects, including increased cell apoptotic ratio, enhancement of apoptosis-related modulator caspase-3 activity, reduced activity levels of such antioxidant enzymes as SOD, CAT, GSH-Px, and MDA upregulation, and inhibited the protein levels of critical endoplasmic reticulum (ER) stress indices like CHOP and GRP78 in mLCs exposed to HS. Besides, treatment of cells with betaine significantly restored diminished testosterone production in response to HS. Correspondingly, betaine effectively rescued the reduced serum testosterone concentration in vivo. In summary, betaine ameliorated HS-induced apoptosis by affecting oxidative and ER stress, thereby providing benefits for the treatment of hyperthermia-related impairment in mLCs.

Response of growth performance and cecum microbial community to cyclic heat stress in broilers.

Heat stress (HS) can affect growth performance through alterations in specific gut microbiota, which greatly threatens poultry production. How HS affects the mechanisms of microbial changes in the poultry cecum and the complex interactions between cecal microbial changes and growth performance have not yet been well evaluated. This study was conducted to examine the changes in growth performance and cecal microbiotal community in cyclic heat stress (CHS)-treated broilers. A total of 200 twenty-eight-day-old female Arbor Acres (AA) broilers were equally allotted into neutral ambient temperature group (TN group, 24 ± 1°C, 24 h/day) and CHS group (33 ± 1°C, 8 h/day) with five replicates of 10 broilers each, respectively. Growth performance, cecum microbial diversity, flora composition, and community structure were analyzed on days 35 and 42. The decreased average daily feed intake (ADFI), average daily gain (ADG), and the increased feed/gain ratio (F:G) were observed in heat-stressed broilers on days 35 and 42. The alpha and beta diversity index had no significant changes at the two experimental periods (P > 0.05). At the genus level, CHS significantly increased the relative abundance of Enterococcus at 42 days (P < 0.05). Based on the analysis of linear effect size feature selection, CHS made an enriched Reyranella and a reduced Romboutsia and Ruminiclostridium at 35 days of age (P < 0.05). CHS made an enriched Weissella and Enterococcus at 42 days of age (P < 0.05). The present study revealed that CHS reduces broiler growth performance and alters the microbial community of the cecum microbiota and the abundance of species. These findings are of critical importance to alleviate the negative effects of CHS on broiler chickens' growth performance by maintaining gut microbial balance.

Effect of dietary supplemental vitamin C and betaine on the growth performance, humoral immunity, immune organ index, and antioxidant status of broilers under heat stress.

Heat stress (HS) has become one of the important factors affecting the development of animal husbandry. The purpose of this experiment was to investigate whether vitamin C (Vc) and betaine (Bet) improve immune organ index and humoral immunity by enhancing the antioxidant status of immune organs, thus protecting broilers from HS-induced injuries. A total of 200 28-day-old Ross 308 broilers were randomly assigned into 5 groups (n = 4 replicates/group, 10 broilers/replicate) which were reared at different ambient temperatures (24 ± 1°C or 33 ± 1°C). The control group fed basal diet, while high-temperature groups were either fed a basal diet (HS group) or a basal diet supplemented with 250-mg Vc/kg diet (HSVc group), 1000-mg Bet/kg diet (HSBet group), and 250-mg Vc plus 1000 mg Bet/kg diet (HSVcBet group), respectively. On day 42, growth performance, humoral immune function, immune organ index, and antioxidant capacity were measured. HS reduced the productive performance of broilers, antibody potency against the Newcastle disease virus (NDV) and sheep red blood cells (SRBC), indices of thymus and bursa, and antioxidant capacity of immune organs. Adding Vc alone or in combination with Bet improved performance, NDV and SRBC antibody potency, thymus and bursa indices, and antioxidant capacity of immune organs in heat-stressed broilers, with the most effective being combination. In summary, HS reduces the antioxidant capacity and immune organ development status of broiler immune organs. Vc and/or Bet can improve the development of immune organs and restore part of the production performance by regulating the antioxidant status of immune organs, among which the combined addition of Vc and Bet has the best effect.

Sodium selenite attenuates zearalenone-induced apoptosis through inhibition of endoplasmic reticulum stress in goat trophoblast cells.

Zearalenone (ZEL)-induced apoptosis in different cells is mediated by various molecular mechanisms, including endoplasmic reticulum (ER) stress. Selenium, an inorganic micronutrient, has several cytoprotective properties, but its potential protective action against ZEL-induced apoptosis in trophoblast cells and the precise mechanisms remain unclear. In this study, we investigated the effects of sodium selenite, a predominant chemical form of selenium, on cell viability, apoptosis, and progesterone (P4) production in ZEL-treated goat trophoblast cell line and explored the underlying molecular mechanisms. ZEL treatment repressed cell viability and promoted apoptosis, which was accompanied by an enhancement of the activity of caspase 3, a key executioner of apoptosis. ZEL treatment was involved in the upregulation of malonaldehyde (MDA) levels and was implicated in the reduction of the protein expression of selenoprotein S (SELS), thereby triggering protein expression of ER stress biomarkers (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP)). However, sodium selenite attenuates these adverse effects, including increases in apoptotic rate, caspase 3 activity, MDA, GRP78, and CHOP expression and decreases in SELS expression in cells treated with ZEL or Thapsigargin (Tg, an ER stress agonist). Simultaneously, 4-phenylbutyric acid (4-PBA, an ER stress antagonist) treatment significantly alleviated the ZEL-induced deleterious effects on cells in response to ZEL, similarly to sodium selenite. In addition, sodium selenite supplementation effectively rescued the ZEL-induced decrease in P4 production in ZEL-treated cells. In summary, these findings suggest that ZEL triggers apoptosis in goat trophoblast cells by downregulating SELS expression and activating the ER stress signaling pathway and that sodium selenite protects against these detrimental effects. This study provides novel insights into the benefits of using selenium against ZEL-induced apoptosis and cellular damage.

Selenium Attenuates Chronic Heat Stress-Induced Apoptosis via the Inhibition of Endoplasmic Reticulum Stress in Mouse Granulosa Cells.

Heat stress induces apoptosis in various cells. Selenium, an essential micronutrient, has beneficial effects in maintaining the cellular physiological functions. However, its potential protective action against chronic heat stress (CHS)-induced apoptosis in granulosa cells and the related molecular mechanisms are not fully elucidated. In this study, we investigated the roles of selenium in CHS-induced apoptosis in mouse granulosa cells and explored its underlying mechanism. The heat treatment for 6-48 h induced apoptosis, potentiated caspase 3 activity, increased the expression levels of apoptosis-related gene BAX and ER stress markers, glucose-regulated protein 78 (GRP78), and CCAAT/enhancer binding protein homologous protein (CHOP) in mouse granulosa cells. The treatment with ER stress inhibitor 4-PBA significantly attenuated the adverse effects caused by CHS. Selenium treatment significantly attenuated the CHS- or thapsigargin (Tg, an ER stress activator)-induced apoptosis, potentiation of caspase 3 activity, and the increased protein expression levels of BAX, GRP78, and CHOP. Additionally, treatment of the cells with 5 ng/mL selenium significantly ameliorated the levels of estradiol, which were decreased in response to heat exposure. Consistently, administering selenium supplement alleviated the hyperthermia-caused reduction in the serum estradiol levels in vivo. Together, our findings indicate that selenium has protective effects on CHS-induced apoptosis via inhibition of the ER stress pathway. The current study provides new insights in understanding the role of selenium during the process of heat-induced cell apoptosis.

Characterization of heat stress affecting the growth performance, blood biochemical profile, and redox status in male and female broilers at market age.

This study investigated the effects of acute heat stress (HS), sex, and their interaction on growth performance, serum biochemical and redox status in the later stage broilers. Two hundred 38-day-old Ross 308 chicks were allocated in a factorial arrangement of 2 × 2 (temperatures and sexes) with 5 replicates of 10 bird each. Thermoneutral and heat-stressed broilers were raised at 24 ± 1 °C or 32 ± 1 °C from day 38 to 39, respectively. HS decreased the average daily feed intake (ADFI) and average daily gain (ADG) whereas it increased feed conversion ratio (FCR), rectal temperature (RT), and respiratory rate (RR) in broilers exposed to high temperature for 24 h and 48 h. Moreover, RT, RR, serum glucose, and HDL-C levels increased while triglyceride (TG), total superoxide dismutase (T-SOD), and glutathione peroxidase (GPx) decreased in broilers exposed to high temperature for 12 h. Male broilers had higher final body weight (FBW), ADFI, ADG, total protein carbonyl group, and lower FCR and T-SOD than females in HS condition for 24 h and 48 h. Lower RT, serum albumin, HDL-C, activities of T-SOD and GPx were observed when compared with those of males in HS condition for 12 h. There were significant temperature × sex interactive effects on ADFI, ADG, and TG in broilers exposed to high temperature for 24 h and 48 h. The present study suggests that the acute HS negatively affects growth performance which is accompanied by the disorder of serum nutritional metabolism and imbalance of redox status in later stage broilers. Some parameters presented sexual differences that suggested it may be more effective to alleviate the negative effects of HS when broiler producers take into account the gender of broiler.

Modular Synthesis of Nona-Decasaccharide Motif from Psidium guajava Polysaccharides: Orthogonal One-Pot Glycosylation Strategy.

The synthesis of long, branched, and complex carbohydrate sequences remains a challenging task in chemical synthesis. Reported here is an efficient and modular one-pot synthesis of a nona-decasaccharide and shorter sequences from Psidium guajava polysaccharides, which have the potent α-glucosidase inhibitory activity. The synthetic strategy features: 1) several one-pot glycosylation reactions on the basis of N-phenyltrifluoroacetimidate (PTFAI) and Yu glycosylation to streamline the chemical synthesis of oligosaccharides, 2) the successful and efficient assembly sequences (first O3', second O5', final O2') toward the challenging 2,3,5-branched Araf motif, 3) the stereoselective 1,2-cis-glucosylation by reagent control, and 4) the convergent [6+6+7] one-pot coupling reaction for the final assembly of the target nona-decasaccharide. This orthogonal one-pot glycosylation strategy can streamline the chemical synthesis of long, branched, and complicated carbohydrate chains.

Sulfatide-activated type II NKT cells suppress immunogenic maturation of lung dendritic cells in murine models of asthma.

Our previous study showed that sulfatide-activated type II natural killer T (NKT) cells can prevent allergic airway inflammation in an ovalbumin (OVA)-induced murine model of asthma, but the underlying mechanism is unclear. Recently, sulfatide-activated type II NKT cells were shown to modulate the function of dendritic cells in experimental autoimmune encephalomyelitis and nonobese diabetic mice. Thus, it was hypothesized that sulfatide-activated type II NKT cells may modulate the function of lung dendritic cells (LDCs) in asthmatic mice. Our data showed that, in our mouse models, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells resulted in reduced expression of surface maturation markers and proinflammatory cytokine production of LDCs. LDCs from sulfatide-treated asthmatic mice, in contrast to LDCs from PBS-treated asthmatic mice, significantly reduced allergic airway inflammation in vivo. However, we found no influence of sulfatide-activated type II NKT cells on the phenotypic and functional maturation of bone marrow-derived dendritic cells in vitro. In addition, adoptive transfer of sulfatide-activated type II NKT cells did not influence the phenotypic and functional maturation of LDCs in CD1d-/- mice, which lack both type I and II NKT cells, immunized and challenged with OVA. Our data reveal that sulfatide-activated type II NKT cells can suppress immunogenic maturation of LDCs to reduce allergic airway inflammation in mouse models of asthma, and it is possible that the immunomodulatory effect needs type I NKT cells.

The Prognostic and Clinicopathological Significance of IGF-1R in NSCLC: a Meta-Analysis.

BACKGROUND/AIMS: Accumulating studies have reported that IGF-1R (Insulin-like growth factor-1 receptor) is aberrantly expressed in NSCLC (non-small cell lung cancer), but the role of IGF-1R in NSCLC remains controversial. The present paper assessed the precise role of IGF-1R in NSCLC. METHODS: We comprehensively searched PubMed, EMBASE, and Web of Science in March 2017. Combined HRs and ORs were used to evaluate the prognostic and clinicopathological significance of IGF-1R in NSCLC respectively. RESULTS: A total of 10 eligible studies including 8 on overall survival, and 10 on clinicopathological features were identified from the databases. The results showed that high expression of IGF-1R was associated with shorter OS (overall survival) of NSCLC patients (pooled HR 1.17,95 % CI 1.00-1.36). In addition, we found that IGF-1R was related to smoking status (OR=1.82, 95 % CI=1.35-2.44) and IGF-1R tended to be highly expressed in SCC (squamous cell carcinoma) (OR=3.40 95 % CI: 1.95-5.95). CONCLUSIONS: In summary, this meta-analysis revealed that high expression of IGF-1R was associated with poor prognosis in NSCLC.

Interactive effects of glutamine and gamma-aminobutyric acid on growth performance and skeletal muscle amino acid metabolism of 22-42-day-old broilers exposed to hot environment.

The present experiment was conducted to investigate the interactive effects between dietary glutamine (Gln, 0 and 5 g/kg) and gamma-aminobutyric acid (GABA, 0 and 100 mg/kg) on growth performance and amino acid (AA) metabolism of broilers under hot environment. A total of 360 22-day-old Arbor Acres male chickens were randomly assigned to five treatment groups under thermoneutral chamber (PC, 23 °C) and cyclic heat stress (HS, 30-34 °C cycling) conditions. Compared with the PC group, cyclic HS decreased (P < 0.05) daily weight gain (DWG), daily feed consumption (DFC), the concentrations of Gln, glutamate (Glu), and GABA, and the activities of glutaminase and glutamic acid decarboxylase (GAD) in breast muscle at 28, 35, and 42 days, while it increased (P < 0.05) the activities of glutamine synthetase (GS) and gamma-aminobutyric acid transaminase (GABA-T) at 28, 35, and 42 days. Dietary Gln and GABA improved (P < 0.05) DWG and DFC of broilers under cyclic HS during 28-42 days. In breast muscle, the Gln supplementation increased (P < 0.05) the concentrations of Gln (28, 35, and 42 days), Glu (28, 35, and 42 days), and GABA (42 days) and the activities of glutaminase (28, 35, and 42 days) and GAD (28, 35, and 42 days) but decreased (P < 0.05) GS activities at 28, 35, and 42 days and GABA-T activities at 28 days. The addition of GABA increased (P < 0.05) the concentrations of Gln and Glu and activities of glutaminase and GAD, while it decreased (P < 0.05) GABA-T activities at 28, 35, and 42 days. Significant interactions (P < 0.05) between Gln and GABA were found on breast skeletal muscle Gln concentrations, glutaminase activities, GS activities at 28 and 35 days, and DWG, GABA concentrations, and GABA-T activities at 28, 35, and 42 days in broilers under cyclic HS. In conclusion, the present results indicated that the interactions of exogenous Gln and GABA could offer a potential nutritional strategy to prevent HS-related depression in skeletal muscle Gln and GABA metabolism of broilers.

Improved Fog Collection on a Hybrid Surface with Acylated Cellulose Coating.

Fog collection serves as an efficient method to alleviate water scarcity in foggy, water-stressed regions. Recent research has focused on constructing a hybrid surface to enhance fog collection efficiency, with one approach being the prevention of liquid film formation at hydrophilic sites. Inspired by the desert beetle, a coating (10-MCC) made by partially acylating microcrystalline cellulose (MCC) exhibits hydrophilic sites alongside a hydrophobic skeleton enabling rapid droplet capture despite its overall hydrophobicity. The captured droplets quickly coalesce into a large droplet driven by the wetting gradient created by the hydrophobic backbone and hydrophilic sites. To achieve greater fog collection efficiency, a hydrophobic-superhydrophobic hybrid surface is formed by combining a coating of 10-MCC with a superhydrophobic surface. The construction of superhydrophobic surfaces typically involves creating a rough surface with a distinctive structure produced by the anodization technique and modifying it with stearic acid. The superhydrophobic surface exhibits excellent corrosion resistance and mechanical stability. Moreover, the hybrid surface shows high efficiency in fog collection, with a tested maximum efficiency of approximately 1.5092 g/cm2/h, 1.77 times that of the original Al sheets. The results demonstrate a remarkable enhancement in fog collection capacity. Furthermore, this work serves as an inspiration for the low-cost and innovative design of engineered surfaces for efficient fog collection.

Non-infectious immune complexes downregulate the production of interferons and tumor necrosis factor-α in primary porcine alveolar macrophages in vitro.

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) has been harming the pig industry worldwide for nearly 40 years. Although scientific researchers have made substantial efforts to explore PRRSV pathogenesis, the immune factors influencing PRRSV infection still need to be better understood. Infectious virus-antibody immune complexes (ICs) formed by PRRSV and sub-or non-neutralizing antibodies specific for PRRSV may significantly promote the development of PRRS by enhancing PRRSV replication through antibody-dependent enhancement. However, nothing is known about whether PRRSV infection is affected by non-infectious ICs (NICs) formed by non-pathogenic/infectious antigens and corresponding specific antibodies. Here, we found that PRRSV significantly induced the transcripts and proteins of interferon-α (IFN-α), IFN-ß, IFN-γ, IFN-λ1, and tumor necrosis factor-α (TNF-α) in vitro primary porcine alveolar macrophages (PAMs) in the early stage of infection. Our results showed that NICs formed by rabbit-negative IgG (RNI) and pig anti-RNI specific IgG significantly reduced the transcripts and proteins of IFN-α, IFN-ß, IFN-γ, IFN-λ1, and TNF-α in vitro PAMs and significantly elevated the transcripts and proteins of interleukine-10 (IL-10) and transforming growth factor-ß1 (TGF-ß1) in vitro PAMs. NICs-mediated PRRSV infection showed that NICs not only significantly decreased the induction of IFN-α, IFN-ß, IFN-γ, IFN-λ1, and TNF-α by PRRSV but also significantly increased the induction of IL-10 and TGF-ß1 by PRRSV and considerably enhanced PRRSV replication in vitro PAMs. Our data suggested that NICs could downregulate the production of antiviral cytokines (IFN-α/ß/γ/λ1 and TNF-α) during PRRSV infection in vitro and facilitated PRRSV proliferation in its host cells by inhibiting innate antiviral immune response. This study elucidated one novel immune response to PRRSV infection, which would enhance our understanding of the pathogenesis of PRRSV.

IL-27 Alleviates Airway Inflammation and Airway Hyperresponsiveness in Asthmatic Mice by Targeting the CD39/ATP Axis of Dendritic Cells.

Interleukin-27 receptor (IL-27R) is expressed in a variety of immune cells and structural cells, including dendritic cells. The mechanism of IL-27 in asthma has not been fully elucidated. This study aimed to examine whether IL-27 regulated the CD39/ATP axis of dendritic cells in asthma. Our results showed that in ovalbumin (OVA)-induced asthma mouse model, IL-27Rα-/- asthmatic mice showed increased airway resistance, increased infiltration of inflammatory cells in lung tissue, proliferation of goblet cells, enhanced expression of Muc5 AC around airway epithelium, increased total number of cells and eosinophils, increased levels of total IgE, OVA-IgE, IL-4, IL-5, IL-13 and IL-17 A, and increased expression of transcription factors GATA-3 and RORγt in lung tissue. The expression of CD39 mRNA and protein in the lung tissue of IL-27Rα-/- asthmatic mice decreased, and the expression of NLRP3, ASC and Caspase-1 in NLRP3 inflammasome components increased. The concentration of ATP was significantly increased compared with WT asthmatic mice. In vitro experiments showed that the expression of CD39 in lung dendritic cells of IL-27Rα-/- asthmatic mice decreased, while the expression of NLRP3 inflammasome components NLRP3, ASC and Caspase-1 increased. These findings indicate that IL-27 directly and indirectly regulates immunoinflammatory responses in asthma by acting on dendritic cells CD39/ATP Axis.

Establishment and engineering application of viscoelastic-plastic constitutive laws for creep modeling in interbedded rock masses.

In order to study the creep behavior of the surrounding rock of the interbedded rock mass tunnel considering the time-dependent deformation, this paper proposes a viscoelastic-plastic seven-element model considering the stress threshold, and derives and establishes its creep equation under three-dimensional stress state. At the same time, the UMAT (User-defined Material) subroutine of the model is developed based on the ABAQUS software. The rationality of the seven-element model and the effectiveness of the subprogram are verified by rheological test results. Finally, the UMAT subroutine is applied to the numerical simulation of the creep behavior of soft and hard interbedded rock tunnels with different rock inclinations (α). The results show that the different rock inclination angles have different effects on the horizontal displacement of the ground above the tunnel, settlement deformation, and the convergence of the tunnel section. With the increase of the rock inclination (0 ≤ α ≤ 90°), the horizontal displacement of the surface on both sides is antisymmetric. When α is 0°, 45° and 90°, the horizontal displacement on both sides is equivalent. Surface subsidence decreases and then increases slowly. When α is 0° and 45°, the surface subsidence is the largest (12.4 mm) and the smallest (11.1 mm), respectively. The convergence values of the tunnel section change according to different parts of the tunnel. The convergence values of the arch top and arch bottom decrease continuously, and their maximum convergence values are 23.4 mm and 17.3 mm, respectively. The change trend of the arch waist and arch shoulder convergence values is the opposite. When α is 0°, the convergence value of the arch waist is maximum (3.5 mm). When α is 15°, the convergence value of the arch shoulder is the maximum (2.0 mm).

MicroRNA-19a Inhibition Directly and Indirectly Ameliorates Th2 Airway Inflammation in Asthma by Targeting RUNX3.

Disruption of T-cell differentiation is characteristic of airway inflammation in allergic asthma. How miR-19a works in asthma has not been completely elucidated. This study aimed to examine whether microRNA-19a regulates helper T-cell proliferation and to identify the factors involved and the underlying mechanisms. Our results showed that miR-19a levels were upregulated in parallel with a reduction in RUNX3 expression in a house dust mite (HDM)-induced murine model of asthma. A dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay showed that RUNX3 was a direct target of miR-19a. Inhibiting the expression of miR-19a attenuated inflammation and mucus production, induced Th1 cells, suppressed the Th2 inflammatory response, and repressed dendritic cell (DC) maturation by increasing RUNX3 expression in WT asthmatic mice but not RUNX3+/- mice. In vitro experiments revealed that miR-19a inhibition could target RUNX3 to induce Th1 polarization and inhibit Th2 polarization by directly acting on naïve CD4+ T cells or indirectly mediating the maturation and antigen-presenting abilities of DCs. These findings indicate that miR-19a directly and indirectly regulates immunoinflammatory responses in asthma by targeting RUNX3.

Antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection downregulates the levels of interferon-gamma/lambdas in porcine alveolar macrophages in vitro.

Fc gamma receptor-mediated antibody-dependent enhancement (ADE) can promote virus invasion of target cells, sometimes exacerbating the severity of the disease. ADE may be an enormous hurdle to developing efficacious vaccines for certain human and animal viruses. ADE of porcine reproductive and respiratory syndrome virus (PRRSV) infection has been demonstrated in vivo and in vitro. However, the effect of PRRSV-ADE infection on the natural antiviral immunity of the host cells is yet to be well investigated. Specifically, whether the ADE of PRRSV infection affects the levels of type II (interferon-gamma, IFN-γ) and III (interferon-lambdas, IFN-λs) interferons (IFNs) remains unclear. In this study, our results showed that PRRSV significantly induced the secretion of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in porcine alveolar macrophages (PAMs) in early infection, and weakly inhibited the production of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in PAMs in late infection. Simultaneously, PRRSV infection significantly increased the transcription of interferon-stimulated gene 15 (ISG15), ISG56, and 2', 5'-oligoadenylate synthetase 2 (OAS2) in PAMs. In addition, our results showed that PRRSV infection in PAMs via the ADE pathway not only significantly decreased the synthesis of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 but also significantly enhanced the generation of transforming growth factor-beta1 (TGF-ß1). Our results also showed that the ADE of PRRSV infection significantly reduced the mRNAs of ISG15, ISG56, and OAS2 in PAMs. In conclusion, our studies indicated that PRRSV-ADE infection suppressed innate antiviral response by downregulating the levels of type II and III IFNs, hence facilitating viral replication in PAMs in vitro. The ADE mechanism demonstrated in the present study furthered our understanding of persistent pathogenesis following PRRSV infection mediated by antibodies.

LOW DOSE OF ESMOLOL ATTENUATES SEPSIS-INDUCED IMMUNOSUPPRESSION VIA MODULATING T-LYMPHOCYTE APOPTOSIS AND DIFFERENTIATION.

ABSTRACT: Background: Immunosuppression caused by immune cell apoptosis and an imbalance of T helper 2 cells (T H 2) and T helper 1 cells (T H 1), is associated with poor outcomes in septic patients. Esmolol was reported to improve survival by modulating immune responses in septic shock. Whether esmolol could alleviate sepsis-induced immunosuppression and the optimal dose are unclear. Methods: Four hours after cecal ligation and puncture (CLP), Wistar rats were randomized into CLP, CLP + E-5 (esmolol: 5 mg·kg -1 ·h -1 ) and CLP + E-18 (esmolol: 18 mg·kg -1 ·h -1 ) groups. Eight rats were underwent sham operation. Eighteen hours after CLP, hemodynamics and organ histological injuries were evaluated, peripheral blood mononuclear cells apoptosis and T-lymphocyte subsets counts were determined by flow cytometry, and the expression of p-Akt, Bcl-2, cleaved Caspase-3, and p-Erk1/2 in splenic CD4 + T-lymphocytes was determined by western blot and immunohistochemistry. ß 1 -Adrenoreceptor expressions were evaluated using real-time polymerase chain reaction and immunohistochemistry. Results: Cecal ligation and puncture induced tachycardia, hypotension, hyperlactatemia, and multiple organ injury. Heart rate was unchanged in the CLP + E-5 group but decreased in the CLP + E-18 group. Hypotension, lactatemia, and multiple organ injuries were improved only in the CLP + E-5 group. T-lymphocyte apoptosis and T H 2/T H 1 ratio was decreased in CLP + E-5 but not in CLP + E-18. p-Akt and Bcl-2 expressions were increased, while cleaved Caspase-3 and p-Erk1/2 expressions were decreased in CLP + E-5. ß 1 -Adrenoreceptor expressions were unchanged in both CLP + E-5 and CLP + E-18 groups. Conclusions: Low dose of esmolol reduced T-lymphocyte apoptosis and restored T H 2/T H 1 ratio in septic shock. Esmolol might modulate Akt/Bcl-2/Caspase-3 pathway to relieve T-lymphocyte apoptosis and inhibit Erk1/2 activity to decrease T H 0 differentiation to T H 2. Esmolol may be a potential immunoregulator of septic shock.