Structural and ultrastructural aspects of the skin of large yellow croaker Larimichthys crocea.

The skin color of the large yellow croaker (Larimichthys crocea) is a crucial indicator to determine its economic value. However, the location of pigment cells in the skin structure is uncertain. To determine the pigment cell type in the skin, the vertical order and ultrastructure of pigment cells were examined using light microscopy and transmission electron microscopy. Both dorsal and ventral skins comprise the epidermis, dermis, and hypodermis. Xanthophores, melanophores, and iridophores were observed in the dermis of the dorsal skin, whereas the latter two were in the dermis of the ventral skin. Interestingly, the size of xanthophores in the dorsal skin was significantly smaller than that of xanthophores in the ventral skin; however, the density of dorsal xanthophores was significantly higher than that of ventral xanthophores. The type L-iridophores with large crystalline structures were observed in the uppermost area of the upper pigment layer, which contributed to the strikingly metallic luster shown by the ventral skin. The melanophores were exclusively found in the dorsal skin, offering the purpose of camouflage. Taken together, our results indicated that the pigment cells display different arrangement patterns between dorsal and ventral skin, and the golden color in the ventral skin results from the coexistence of light-reflecting iridophores and light-absorbing xanthophores.

Drug suspending during wound healing effectively weakens immunosuppression-related complications by preserving CD8+ T cell function.

Immunosuppressive medications, which interfere with the activation and proliferation of T and B cells, increase the risk of wound healing complications. To address it, this study aimed to validate the feasibility of drug suspending during wound healing, whilst exploring the mechanisms exerted by T cells, which are important in the wound healing process. For this, a mouse skin wound model was set up. Tacrolimus (FK506) and fingolimod (FTY720) were both administered intraperitoneally prior to wounding to inhibit the T cell activation and migration, respectively. Flow-cytometric analysis subsequently revealed the functional T cell subtypes detected during the healing process. A CD8a antibody was also administered to deplete CD8+ T cells in vivo to verify their specific function. It was found that FK506 or FTY720 administration delayed the early phase of wound healing by reducing collagen production, which was also supported by the downregulation of col1a1, col3a1 and tgfb1. However, there was no significant difference in the total healing period. Both spleen- and skin-derived CD8+ T cells were proliferated and activated after injury without intervention, whereas CD4+ T cells showed no significant changes. Furthermore, selectively depleting CD8+ T cells retarded the healing process by downregulating collagen production-associated genes (col1a1, col3a1, tgfß1 and en1) and proteins (collagen type 1 and 3). In addition, the CD8a antibody decreased the expression of genes lta, tnfa, il13 and il13ra, and protein interleukin-13Rα. In conclusion, suspending immunosuppressive drugs during wound healing was shown to be feasible through restraining the migration of activated T cells. CD8+ T cells represented the primary functional subtype positively associated with wound healing.

Effects of SARS-CoV-2 vaccine (Vero cells) on disease activity in patients with inflammatory bowel disease in China: a multicenter study.

AIMS: To evaluate the impact of SARS-CoV-2 vaccine on IBD activity. METHODS: Adult IBD patients from five large IBD centers in China were enrolled and followed up for 6 months. Patients were divided into vaccinated and unvaccinated groups according to vaccination status. Demographic and clinical data were collected. RESULTS: A total of 280 individuals (213 UC and 67 CD patients) were enrolled in the study. The unvaccinated and vaccinated groups of UC patients were comparable for basic characteristics, including age (t = - 0.8, p = 0.425), sex (χ2 = 0.980, p = 0.322), course of disease (z = - 0.513, p = 0.608), surgical conditions (χ2 = 1.042, p = 0.838), disease extent (χ2 = 4.853, p = 0.088), or baseline drug therapy (χ2 = 7.784, p = 0.064). In the subgroup of UC patients, there was no association between vaccination and disease activities, according to the medium disease activity scores for two groups: unvaccinated patients having scores (IQR) 1(2.75), 1(2), 1(2), and 1(2) at baseline, 1, 3, and 6 months, respectively, whereas vaccinated patients having scores (IQR) 1(2), 1(2), 1(2), and 1(2). Similar conclusions were also derived in the subgroup of CD patients. There were also no statistically significant differences in age (t = - 1.48, p = 0.144), sex (χ2 = 0.003, p = 0.957), course of disease (z = - 0.074, p = 0.941), surgical conditions (χ2 = 0.613, p = 0.594), localization (χ2 = 6.261, p = 0.199), or baseline drug therapy (χ2 = 5.881, p = 0.114) between 2 groups of CD patients. The medium disease activity scores (IQR) of the unvaccinated group at baseline, 1, 3, and 6 months were 1(4), 1(3), 1(3), and 1(3), respectively, whereas those of vaccinated group were 2.5(3.75), 2.5(3.75), 3(2), and 2(2), respectively. Overall, very few participants in this study described worsening IBD disease activity requiring a change or addition of medication. CONCLUSIONS: SARS-CoV-2 vaccine has no adverse effect on disease activity in IBD population. IBD patients should be recommended to receive SARS-CoV-2 vaccine in time.

Cinnamtannin D1 attenuates autoimmune arthritis by regulating the balance of Th17 and treg cells through inhibition of aryl hydrocarbon receptor expression.

The suppression of the abnormal systemic immune response constitutes a primary strategy for treatment of rheumatoid arthritis (RA); toward this end, the identification of natural compounds with immunosuppressive activity represents a promising strategy for RA drug discovery. Cinnamtannin D1 (CTD-1), a polyphenolic compound isolated from Cinnamomum tamala, was previously reported to possess good immunosuppressive activity. However, the beneficial effect of CTD-1 on RA is currently unknown. The aim of this study was to evaluate the anti-arthritic effect of CTD-1 in collagen-induced arthritis (CIA) mice and clarify the underlying mechanisms. CTD-1 treatment significantly alleviated the severity of CIA mice, affording reduced clinical scores and paw swelling, along with reduced inflammatory cell infiltration and cartilage damage in the joints; in addition, the serum levels of IL-17, IL-6, and IL-1ß were decreased whereas those of TGF-ß and IL-10 were increased. CTD-1-treated mice exhibited lower frequency of Th17 cells and higher frequency of Treg cells compared to those in untreated mice, indicating that the balance of Th17/Treg cells may serve as the target for CTD-1. Consistent with this, in ex vivo assays, CTD-1 inhibited Th17 cell differentiation through the downregulation of phospho-STAT3/RORγt, whereas it promoted Treg differentiation by upregulating phospho-STAT5/Foxp3 in response to the stimulation of collagen type II. Moreover, in an in vitro naïve CD4+ T cell differentiation assay, CTD-1 directly inhibited Th17 cell differentiation and promoted Treg differentiation, suggesting that CTD-1 regulated the balance of Th17 and Treg cells to inhibit excessive immune response. Furthermore, the regulation effect of CTD-1 on Th17 and Treg cells was dependent on Ahr expression, as this effect was abolished when Ahr was knocked down and was impaired when Ahr was overexpressed. Together, our results indicated that CTD-1 treatment benefits CIA mice by regulating Th17 and Treg differentiation through the inhibition of AHR expression, and suggested a potential application of CTD-1 toward RA treatment.

Ranking effect in air pollution governance: Evidence from Chinese cities.

Information disclosure in environmental governance, or informational governance conceptualized by Arthur Mol, has been increasingly utilized as a policy instrument to incentivize environmental policy enforcement in not only democratic societies but also authoritarian regimes like China. This study uses an explicit regulation, the air pollution ranking in Chinese cities as an example to illustrate how such informational governance policy instrument has an impact on local air pollution governance. Empirical evidence is based on monthly comprehensive air quality index ranking data of 74 key monitoring cities in China from 2013 to 2018. And a regression discontinuity design is applied to explore the relationship between air pollution ranking and air quality improvement in localities. The results show that (1) air quality of the bottom ten cities in the ranking will improve in the coming month compared with their counterparts; (2) such improvement happens upon the releasing of the ranking, but would not last for more than a month; (3) while top ten cities in the ranking do not experience such change in air quality. Therefore, we argue that the air pollution ranking system in China can be a useful informational governance instrument in providing negative incentives for environmental administrations in bottom cities to strengthen air pollution control. However, as a top-down environmental information disclosure program, such ranking institution could only mobilize local air quality governance temporarily. And new institutions ought to be established to further internalized local governments' environmental externalities.

Material basis studies of anti-Influenza A active ingredients in Tanreqing Injection.

Tanreqing Injection (TRQ) has been used primarily in treating infections of the upper respiratory tract and serious influenza in China, as a classical compound herbal recipe. TRQ had been demonstrated to have effects of clearing heat, eliminating phlegm, detoxification, reducing inflammation and alleviating cough. The survival rate, histopathology of lungs and viral titers in mice were evaluated in this study to verify the curative effect of TRQ. However, there is not enough information about the components. In the present study, a high-performance and practical LC/QTOF/MS method was developed for characterization and identification of the natural ingredients in TRQ. A total of 60 compounds, including 10 amino acids, 10 iridoid glucosides, 14 flavonoids, 13 other phenolic compounds, 10 steroid acids and three other compounds, were characterized and identified. We also confirmed the material basis of anti-Influenza A active ingredients in TRQ. Therefore, we have developed an accurate analytical method. LC/QTOF/MS could be applied for identification the complex components in traditional Chinese medicine.

Anti-inflammatory and immunoregulatory functions of artemisinin and its derivatives.

Artemisinin and its derivatives are widely used in the world as the first-line antimalarial drug. Recently, growing evidences reveal that artemisinin and its derivatives also possess potent anti-inflammatory and immunoregulatory properties. Meanwhile, researchers around the world are still exploring the unknown bioactivities of artemisinin derivatives. In this review, we provide a comprehensive discussion on recent advances of artemisinin derivatives affecting inflammation and autoimmunity, the underlying molecular mechanisms, and also drug development of artemisinins beyond antimalarial functions.

Prediction of pedicled flap survival preoperatively by operating indocyanine green angiography at 1,450 nm wavelength: an animal model study.

Background: Predicting flap viability benefits patients by reducing complications and guides flap design by reducing donor areas. Due to varying anatomy, obtaining individual vascular information preoperatively is fundamental for designing safe flaps. Although indocyanine green angiography (ICGA) is a conventional tool in intraoperative assessment and postoperative monitoring, it is rare in preoperative prediction. Methods: ICGA was performed on 20 male BALB/c mice under five wavelengths (900/1,000/1,100, /1,250/1,450 nm) to assess vascular resolution after ICG perfusion. A "mirrored-L" flap model with three angiosomes was established on another 20 male BALB/c mice, randomly divided into two equal groups. In Group A, a midline between angiosomes II and III was used as a border. In Group B, the points of the minimized choke vessel caliber marked according to the ICG signal at 1,450 nm wavelength (ICG1450) were connected. Necrotic area calculations, pathohistological testing, and statistical analysis were performed. Results: The vascular structure was clearly observed at 1,450 nm wavelength, while the 900 to 1,100 nm failed to depict vessel morphology. Necrosis was beyond the borderline in 60% of Group A. Conversely, 100% of Group B had necrosis distal to the borderline. The number of choke vessels between angiosomes II and III was positively correlated with the necrotic area (%). The pathohistological findings supported the gross observation and analysis. Conclusion: ICG1450 can delineate the vessel structure in vivo and predict the viability of pedicled skin flaps using the choke vessel as the border between angiosomes.

Otitis media with effusion in preschool children with adenoid hypertrophy: Risk factors and nursing care.

AIM: To evaluate the influencing factors of otitis media with effusion (OME) in children with adenoid hypertrophy and to provide evidence for clinical treatment and care of children with adenoid hypertrophy. DESIGN: A retrospective study. METHODS: Preschool children with adenoid hypertrophy treated in our hospital from 1 January 2021 to 30 July 2022 were included. We analysed the characteristics of OME and non-OME children with adenoid hypertrophy. Pearson correlation analysis and logistic regression analysis were performed to evaluate the risk factors for OME in children with adenoid hypertrophy. CONCLUSION: A total of 166 children with adenoid hypertrophy were included; the incidence of OME in children with adenoid hypertrophy was 34.94%. The incidence of OME decreased significantly with the increase in age (p = 0.014). Logistic regression analysis showed that age < 3 years (OR = 3.149, 95%CI: 2.812-3.807) and duration of adenoid hypertrophy ≥12 months (OR = 2.326, 95%CI: 2.066-2.612) were the risk factors of OME in children with adenoid hypertrophy (all p < 0.05). PATIENT CONTRIBUTION: The incidence of adenoid hypertrophy with OME is high in preschool children, and it is related to the age and duration of adenoid hypertrophy.

Identification and characterization of a TLR4 homologue in Eriocheir sinensis based on structure analysis.

Toll-like receptor 4 (TLR4) plays an essential role in the activation of innate immunity by recognizing diverse pathogenic components of bacteria. Six Tolls were found in Eriocheir sinensis but have not yet been identified as mammalian TLR4 homolog. For this purpose, we predicted three-dimensional (3D) structures of EsTolls (EsToll1-6) with AlphaFold2. 3D structure of LRRs and TIR most had high accuracy (pLDDT >70). By structure analysis, 3D structures of EsToll6 had a high overlap with HsTLR4. Moreover, we also predicted potential 11 hydrogen bonds and 3 salt bridges in the 3D structure of EsToll6-EsML1 complex. 18 hydrogen bonds and 7 salt bridges were predicted in EsToll6-EsML2 complex. Co-immunoprecipitation assay showed that EsToll6 could interact with EsML1 and EsML2, respectively. Importantly, TAK242 (a mammalian TLR4-specific inhibitor) could inhibit the generation of ROS stimulated by lipopolysaccharides (LPS) in EsToll6-EsML2-overexpression Hela cells. Collectively, these results implied that EsToll6 was a mammalian TLR4 homolog and provided a new insight for researching mammalian homologs in invertebrates.

Characterization of DmToll and DmToll7 homologue in Litopenaeus vannamei based on structure analysis.

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that recognize invading pathogens and activate downstream signaling pathways. The number of 10 Tolls is found in Litopenaeus vannamei but have not yet been identified as the corresponding Toll homologue of model animal. In this study, we predicted the three-dimensional (3D) structures of 10 LvTolls (LvToll1-10) with AlphaFold2 program. The per-residue local distance difference test (pLDDT) scores of LvTolls showed the predicted structure of LvTolls had high accuracy (pLDDT>70). By structural analysis, 3D structures of LvToll2 and LvToll3 had high similarity with Drosophila melanogaster Toll and Toll7, respectively. 3D structure of LvToll7 and LvToll10 were not similar to that of other LvTolls. Moreover, we also predicted that LvSpätzle4 had high structural similarity to DmSpätzle. There were 9 potential hydrogen bonds in LvToll2-LvSpätzle4 complex. Importantly, co-immunoprecipitation assay showed that LvToll2 could bind with LvSpätzle4. Collectively, this study provides new insight for researching invertebrate immunity by identifying the protein of model animal homologue.

Nonvisual system-mediated body color change in fish reveals nonvisual function of Opsin 3 in skin.

Body-color changes in many poikilothermic animals can occur quickly. This color change is generally initiated by visual system, followed by neuromuscular or neuroendocrine control. We have previously showed that the ventral skin color of the large yellow croaker (Larimichthys crocea) presents golden yellow in dark environment and quickly changes to silvery white in light environment. In the present study, we found that the light-induced whitening of ventral skin color was independent of visual input. Using light-emitting diode sources of different wavelength with same luminance (150 lx) but different absolute irradiance (0.039-0.333 mW/cm2), we further found that the blue light (λmax = 480 nm, 0.107 mW/cm2) is more effectively in induction of whitening of ventral skin color in compare with other light sources. Interestingly, the result of RT-PCR showed opsin 3 transcripts expressed in xanthophores. Recombinant protein of Opsin 3 with 11-cis retinal formed functional blue-sensitive pigment, with an absorption maximum at 468 nm. The HEK293T cells transfected with Opsin 3 showed a blue light-evoked Ca2+ response. Knock-down of Opsin 3 expression blocked the light-induced xanthosomes aggregation in vitro. Moreover, the light-induced xanthosomes aggregation was mediated via Ca2+-PKC and Ca2+-CaMKII pathways, and relied on microtubules and dynein. Decrease of cAMP levels was a prerequisite for xanthosomes aggregation. Our results provide a unique organism model exhibiting light-induced quick body color change, which was independent of visual input but rather rely on non-visual function of Opsin 3 within xanthophore.

Mannan-binding lectin inhibits oxidative stress-induced senescence via the NAD+/Sirt1 pathway.

Prolonged or excessive oxidative stress can lead to premature cellular and body aging. Mannan-binding lectin (MBL) is synthesized by the liver and plays an important role in innate immunity, anti-inflammation, and anti-oxidation, and has a positive impact on health and longevity. To date, few studies investigated the role of MBL in attenuating oxidative stress-induced senescence. In this study, we evaluated the role of MBL in oxidative stress-induced premature aging and explored its underlying mechanism in C57BL/6 mice and mouse embryonic fibroblasts (NIH/3T3). First, we established an oxidative premature senescence model induced by D-galactose in C57BL/6 mice. We found that MBL-deficient mice had a marked aging-like appearance, reduced learning and spatial exploration abilities, severe liver pathological damage, and significantly upregulated expression of Senescence-associated proteins (p53 and p21), inflammatory kinesins (IL-1ß and IL-6), and the senescence ß-galactosidase (SA-ß-Gal) positive rate as compared with WT mice. In the H2O2-induced oxidative senescence model of NIH/3T3 cells, consistent results were obtained after MBL intervention. In addition, MBL effectively inhibited G1 phase arrest, ROS levels, DNA damage, and mitochondrial dysfunction in premature senescent cells. Mechanistically, we found that oxidative stress inhibited the nicotinamide adenine dinucleotide (NAD+)/ silent information regulator 1 (Sirt1) signaling pathway, while MBL activated the NAD+/Sirt1 signaling pathway inhibited by oxidative stress. In addition, MBL could activate the NAD+/Sirt1 pathway by upregulating NAMPT, which in turn inhibited p38 phosphorylation by activating the NAD+/Sirt1 pathway. In conclusion, MBL inhibits oxidative aging, which may facilitate the development of therapeutics to delay oxidative aging.

Systematic Structural Modification of Squaraine Dye for Near-Infrared Window One and Two Multiplexed In Vivo Imaging and Photothermal Therapy.

Due to the wide application of reporter gene-related visible/NIR-I bioluminescent imaging, multiplexed fluorescence imaging across visible/NIR-I/NIR-II has excellent potential in biomedical research. However, in vivo multiplexed imaging applications across those regions have rarely been reported due to the lack of proper fluorophores. Herein, nine squaraine dyes, which exhibit diverse adsorption and emission wavelengths, were synthesized. Among them, water-soluble SQ 710-5k and SQ 905 were found to have significant absorption differences, which allowed the tumor and lymph nodes to be identified. Then, for the first time, six-channel multiplexed fluorescence imaging across visible/NIR-I/II was achieved by coordination with reporter gene-related bioluminescent phosphors. Additional research revealed that SQ 710-5k exhibited higher-quality blood vessels and tumor imaging in NIR-II. H-aggregates SQ 905 demonstrated a high photothermal conversion efficiency for photothermal therapy. This study proposed an approach to creating small molecular dyes that coordinate with reporter gene-related bioluminescent phosphors for six-color fluorescence imaging.

Obesity Exacerbates Acute Gastrointestinal Injury and Intestinal Barrier Dysfunction in Early-Stage Acute Pancreatitis.

BACKGROUND: The impact of obesity on the severity of acute pancreatitis and subsequent acute gastrointestinal injury remains an important consideration. This study aimed to determine the clinical relationship between obesity and acute gastrointestinal injury in earlystage acute pancreatitis. METHODS: This was a prospective study that enrolled 194 acute pancreatitis patients. RESULTS: The median body mass index was 26.5 (7.0) kg/m2. Considering etiology of acute pancreatitis, 90 patients had gallstones, 48 had hypertriglyceridemia, 36 were alcohol users, and 20 were others. A total of 116 patients had mild acute pancreatitis and the rest had severe acute pancreatitis. The median of bedside index of severity in acute pancreatitis score was 1 (2) and the serum concentration of C-reactive protein was 80.5 (60.0) mg/L. Acute pancreatitis was accompanied by multiple organ dysfunction in 60 cases and by pancreatic necrosis in 34. A total of 52 patients were admitted to intensive care unit. The values of body mass index were higher in patients with severe acute pancreatitis than those with mild acute pancreatitis. A similar trend emerged in patients with hyperlipidemic acute pancreatitis compared to other causes. Body mass index had a positive relationship with bedside index of severity in acute pancreatitis scores. Noticeably, body mass index was statistically raised from gastrointestinal injury grade 1 to grade 4. The values of body mass index also showed relevance with intestinal barrier function evaluated by d-lactate, diamine oxidase, and intestinal fatty acid binding proteins. Furthermore, body mass indexes were statistically higher in patients having adverse outcomes of acute pancreatitis. CONCLUSION: This prospective study showed that obesity might contribute to increasing the severity of acute pancreatitis and aggravate subsequent intestinal injury in early-stage acute pancreatitis.

Responses of root characteristics and nitrogen absorption and assimilation to different pH gradients of winter wheat at seedling stage.

Nitrogen (N) and rhizosphere pH are the two main factors restricting the growth of winter wheat (Triticum aestivum L.) in North China Plain. Soil nutrient availability is affected by soil acidity and alkalinity. In order to understand the effect of rhizosphere pH value on wheat nitrogen metabolism and the response of wheat growth to pH value at seedling stage, winter wheat varieties 'Aikang 58' (AK58) and 'Bainong 4199' (BN4199) were tested in hydroponics under three pH treatments (pH = 4.0, 6.5, and 9.0). The results showed that the accumulation of dry matter in root and above ground under pH 4.0 and pH 9.0 treatments was lower than that under pH 6.5 treatments, and the root/shoot ratio increased with the increase of pH value. Regardless of pH value, 'BN4199' had higher root dry weight, root length, root surface area, root activity and root tip than 'AK58'. Therefore, wheat that is tolerant to extreme pH is able to adapt to the acid-base environment by changing root characteristics. At pH 4.0, the net H+ outflow rate of wheat roots was significantly lower than that of the control group, and the net NO3- flux of wheat roots was also low. The net H+ outflow occurred at pH 6.5 and 9.0, and at the same time, the net NO3- flux of roots also increased, and both increased with the increase of pH. The activity of nitrate reductase (NR) in stem of pH 9.0 treatment was significantly higher than that of other treatments, while the activity of glutamine synthetase (GS) in root and stem of pH 6.5 treatment was significantly higher than that of other treatments. Under pH 4.0 and pH 9.0 treatments, the activities of NR and GS in 'BN4199' were higher than those in 'AK58', The root respiration of 'BN4199' was significantly higher than that of 'AK58' under pH 4.0 and pH 9.0 treatment, and 'BN4199' had higher NO3- net flux, key enzyme activity of root nitrogen metabolism and root respiration. Therefore, we believe that 'BN4199' has strong resistance ability to extreme pH stress, and high root/shoot ratio and strong root respiration can be used as important indicators for wheat variety screening adapted to the alkaline environment at the seedling stage.

Vunakizumab-IL22, a Novel Fusion Protein, Promotes Intestinal Epithelial Repair and Protects against Gut Injury Induced by the Influenza Virus.

Secondary immune damage to the intestinal mucosa due to an influenza virus infection has gained the attention of investigators. The protection of the intestinal barrier is an effective means of improving the survival rate in cases of severe pneumonia. We developed a fusion protein, Vunakizumab-IL22(vmab-IL22), by combining an anti-IL17A antibody with IL22. Our previous study showed that Vunakizumab-IL22 repairs the pulmonary epithelial barrier in influenza virus-infected mice. In this study, we investigated the protective effects against enteritis given its anti-inflammatory and tissue repair functions. The number of goblet cells and the expression of zonula occludens protein 1(ZO-1), Mucin-2, Ki67 and IL-22R were determined by immunohistochemistry (IHC) and quantitative RT-PCR in influenza A virus (H1N1)-infected mice. The expression of NOD-like receptor pyrin domain containing 3 (NLRP3) and toll- like-receptor-4 (TLR4) was assayed by IHC in the lungs and intestine in HIN1 virus-induced mice to evaluate the whole efficacy of the protective effects on lungs and intestines. Consequently, Cytochrome C, phosphorylation of nuclear factor NF-kappaB (p-NF-κB), IL-1ß, NLRP3 and Caspase 3 were assayed by Western blotting in dextran sulfate sodium salt (DSS)-treated mice. Treatment with Vunakizumab-IL22 improved the shortened colon length, macroscopic and microscopic morphology of the small intestine (p < 0.001) significantly, and strengthened the tight junction proteins, which was accompanied with the upregulated expression of IL22R. Meanwhile, Vunakizumab-mIL22 inhibited the expression of inflammation-related protein in a mouse model of enteritis induced by H1N1 and DSS. These findings provide new evidence for the treatment strategy for severe viral pneumonia involved in gut barrier protection. The results suggest that Vunakizumab-IL22 is a promising biopharmaceutical drug and is a candidate for the treatment of direct and indirect intestinal injuries, including those induced by the influenza virus and DSS.

Urbanization Impact on Regional Sustainable Development: Through the Lens of Urban-Rural Resilience.

The urban-rural system is an economically, socially, and environmentally interlinked space, which requires the integration of industry, space, and population. To achieve sustainable and coordinated development between urban and rural systems, dynamic land use change within the urban-rural system and the ecological and social consequences need to be clarified. This study uses system resilience to evaluate such an impact and explores the impact of land use change, especially land conversion induced by urbanization on regional development through the lens of urban-rural resilience. The empirical case is based on the Beijing-Tianjin-Hebei Urban Agglomeration (BTHUA) in China from 2000 to 2020 when there was rapid urbanization in this region. The results show that along with urbanization in the BTHUA, urban-rural resilience is high in urban core areas and low in peripheral areas. From the urban core to the rural outskirts, there is a general trend that comprehensive resilience decreases with decreased social resilience and increased ecological resilience in this region. Specifically, at the city level, comprehensive resilience decreases sharply from the urban center to its 3-5 km buffer zone and then remains relatively stable in the rural regions. A similar trend goes for social resilience at the city level, while ecological resilience increases sharply from the urban center to its 1-3 km buffer zone, and then remains relatively stable in the rural regions in this region, except for cities in the west and south of Hebei. This study contributes to the conceptualization and measurement of urban-rural resilience in the urban-rural system with empirical findings revealing the impact of rapid urbanization on urban-rural resilience over the last twenty years in the BTHUA in China. In addition, the spatial heterogeneity results could be used for policy reference to make targeted resilience strategies in the study region.

Intestinal microbiota metabolizing Houttuynia cordata polysaccharides in H1N1 induced pneumonia mice contributed to Th17/Treg rebalance in gut-lung axis.

Influenza A virus is intricately linked to dysregulation of gut microbiota and host immunity. Previous study revealed that Houttuynia cordata polysaccharides (HCP) exert the therapeutic effect on influenza A virus inducing lung and intestine damage via regulating pulmonary and intestinal mucosal immunity. However, whether this result was due to the regulation of gut microbiota in the gut-lung axis remains unclear. Here, we firstly found that the elimination of gut microbiota using antibiotic cocktails led to both loss of the protective effect of HCP on intestine and lung injury, and reduction of the efficacy on regulating Th17/Treg balance in gut-lung axis. Fecal microbiota transplantation study confirmed that the gut microbiota fermented with HCP under pathological conditions (H1N1 infection) was responsible for reducing pulmonary and intestinal injury. Moreover, the interaction of HCP and gut microbiota under pathological conditions exhibited not only much more abundant gut microbial diversity, but also higher content of the acetate. Our results demonstrated that the underlying mechanism to ameliorate viral pneumonia in mice involving Th17/Treg rebalance via the gut microbiota and HCP metabolite (acetate) metabolized in pneumonia mice. Our results provided a new insight for macromolecular polysaccharides through targeting intestinal microenvironment reducing distant pulmonary infection.

Houttuynia cordata polysaccharides alleviate ulcerative colitis by restoring intestinal homeostasis.

Houttuynia cordata is traditionally used as phytoantibiotics for treating lung disease in China. Houttuynia cordata polysaccharides (HCPs) have been reported to alleviate influenza virus-induced intestinal and lung immune injury by regulating the gut-lung axis. The present study aims to investigate the effects and mechanisms of HCPs on ulcerative colitis (UC). Male C57BL/6 mice were induced by dextran sodium sulfate (DSS) to establish the UC animal model. Our results showed that HCPs significantly reduced the weight loss and the shortening of colon length in colitis mice, and relieved the pathological damage of colon mucosa and inhibited the expression of pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, etc. It was suggested that HCPs could significantly improve DSS-induced colitis in mice. HCPs directly protected intestinal epithelial cells, ameliorated epithelial barrier dysfunction and cell apoptosis, which was also proved in H2O2 stimulated cell apoptosis model. HCPs inhibited inflammation in the colon, which was related to suppressing the infiltration of macrophages, inhibiting the expression of pro-inflammatory cytokines and proteins (TLR4, NF-κB), and restoring the dysfunction of Th17 and Treg cells. HCPs also restored the alteration of intestinal flora induced by DSS, increased the abundance ofFirmicutes and Bacteroides, and reduced the abundance of Proteobacteria. This study confirmed the protective effect of Houttuynia cordata polysaccharide extracted from traditional Chinese medicine on ulcerative colitis, of which the mechanism was closely related to the maintenance of intestinal homeostasis (intestinal barrier, immune cells, and intestinal bacteria).