Summary Surgical site infections (SSIs) are the most common health-care-associated infections in developing countries, but they also represent a substantial epidemiological burden in high-income ...countries. The prevention of these infections is complex and requires the integration of a range of preventive measures before, during, and after surgery. No international guidelines are available and inconsistencies in the interpretation of evidence and recommendations in national guidelines have been identified. Considering the prevention of SSIs as a priority for patient safety, WHO has developed evidence-based and expert consensus-based recommendations on the basis of an extensive list of preventive measures. We present in this Review 16 recommendations specific to the intraoperative and postoperative periods. The WHO recommendations were developed with a global perspective and they take into account the balance between benefits and harms, the evidence quality level, cost and resource use implications, and patient values and preferences.
Polyaspartic acid (PASP) is a macromolecule compound with carboxylic acid side chains which is polymerized by L-aspartic acid, has been used as a biodegradable and environmentally-friendly chelating ...agent to enhance the phytoremediation of heavy metal-contaminated soils. Cadmium (Cd) is a toxic element for plant growth, productivity, and food security. To reveal the responses of PASP to plant physiology and morphology under Cd stress, we comprehensively analyzed soil characteristics, cell ultrastructure, reactive oxygen species (ROS), antioxidant enzymes, Cd uptake, transport, subcellular distribution, cell wall compositions, and their Cd chelating capacity in rapeseed. The results showed PASP increased the content of total N, total P, and available P in soil by 3.4%, 28.6%, and 39.8%, respectively, but did not change soil pH and available Cd. Meanwhile, PASP promoted dry mass accumulation and increased photosynthetic pigment content in rapeseed leaves by maintaining the chloroplast structure. Lower malondialdehyde (MDA) content and hydrogen peroxide (H2O2) accumulation and activated antioxidant enzymes in leaves indicate that PASP contributed to relieving Cd-induced oxidative damage to cells of rapeseed leaves. The results indicated that PASP application increased the Cd distribution ratio in root cell walls from 47.4% to 62.3% and decreased the Cd content in xylem sap by 37.8%, which ultimately reduced Cd reallocation in leaves. Additionally, higher pectin content and Cd in pectin resulted in higher Cd retention in leaf cell walls while reducing its concentration in the organelle fraction. The results indicated that 0.3% PASP effectively alleviated Cd stress in rapeseed leaves by inhibiting Cd transportation from roots, activating antioxidant enzymes to scavenge ROS, and promoting Cd chelation by cell wall pectin in leaves.
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•Cadmium (Cd) pollution is a major restriction for crop production and quality.•Polyaspartic acid (PASP) inhibited root-shoot translocation of Cd in rapeseed.•More Cd fixation in root cell walls decreased transport of Cd in xylem.•Higher pectin content and stronger Cd chelation on pectin in leaves enhanced Cd resistance of rapeseed leaves.
Boron (B) deficiency and toxicity are the major factors that affect plant growth and yield. The present study revealed the effect of B deficiency and toxicity on plant growth, morphology, physiology, ...and cell structure. A hydroponic culture experiment was conducted with five B levels, B deficient (B0), sufficient (B20, B10, B40) and toxic (B100). Our results show that both B deficient as well as excess level inhibit plant growth. In B deficiency, the major visible symptoms were appeared in roots, while B excess burned the leaf margin of older leaves. The antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) decreased at B deficiency and also decreased up to some extent at B excess, while in sufficient treatments, the higher antioxidant enzymes were found at B20. In addition, the MDA concentration decreased at B deficiency and increased with B concentration. Moreover, the photosynthetic rate, transpiration rate, stomatal conductance, leaf gas exchange and intercellular CO2 were reduced at both B deficiency as well as excess and higher at sufficient B20 treatment significantly. The chlorophyll and carotenoid content increased at B20 treatment, while decreased at B deficiency and excess. The middle lamellae of cell wall were found thick at B excess and normal at B20. The current study revealed that B deficiency as well as excess concentration affect plant growth and various morpho-physiological processes.
•Boron is an important micronutrient needed for plant growth and development.•Deficiency and toxicity of B appeared symptoms in citrange orange and inhibited its growth.•Antioxidant enzymes were altered by B deficiency and toxicity.•The optimum B concentration for citrange orange was found 20mg/liter.
Abstract
The STING pathway and its induction of autophagy initiate a potent immune defense response upon the recognition of pathogenic DNA. However, this protective response is minimal, as STING ...activation worsens organ damage, and abnormal autophagy is observed during progressive sepsis. Whether and how the STING pathway affects autophagic flux during sepsis-induced acute lung injury (sALI) are currently unknown. Here, we demonstrate that the level of circulating mtDNA and degree of STING activation are increased in sALI patients. Furthermore, STING activation was found to play a pivotal role in mtDNA-mediated lung injury by evoking an inflammatory storm and disturbing autophagy. Mechanistically, STING activation interferes with lysosomal acidification in an interferon (IFN)-dependent manner without affecting autophagosome biogenesis or fusion, aggravating sepsis. Induction of autophagy or STING deficiency alleviated lung injury. These findings provide new insights into the role of STING in the regulatory mechanisms behind extrapulmonary sALI.
Aluminium (Al) toxicity is the most important soil constraint for plant growth and development in acid soils (pH < 5.5) globally in agricultural regions. Boron (B) is an essential micronutrient for ...the growth and development of higher plants. The results of previous studies propose that B might ameliorate Al toxicity; however, none of the studies have been conducted on trifoliate orange to study this effect. Thus, a study was carried out in hydroponics comprising of two different Al concentrations, 0 and 400 μM. For every concentration, two B treatments (0 and 10 μM as H3BO3) were applied to investigate the B-induced alleviation of Al toxicity and exploring the underneath mechanisms. The results revealed that Al toxicity under B deficiency severely hampered the root growth and physiology of plant, caused oxidative stress and membrane damage, leading to severe root injury and damage. However, application of B under Al toxicity improved the root elongation and photosynthesis, while reduced Al uptake and mobilization into plant parts. Moreover, B supply regulated the activities of antioxidant enzymes, proline, secondary metabolites (phenylalanine ammonia lyase and polyphenol oxidase) contents, and stabilized integrity of proteins. Our study results imply that B supply promoted root growth as well as defense system by reducing reactive oxygen species (ROS) and Al concentrations in plant parts thus B induced alleviation of Al toxicity; a fact that might be significant for higher productivity of agricultural plants grown in acidic conditions.
•Boron (B) supply improves root elongation under Al toxicity.•B supply eliminates oxidative stress and Al induced root cell injury by regulating antioxidant defense system.•The B-induced alleviation of Al toxicity might be associated with the reduced uptake of Al.
The distribution of boron (B) in leaves is far from uniform, and tolerance to B toxicity should be varied in different portions of an entire leaf. Here, according to the order and degree of leaf ...chlorosis, a whole leaf blade of trifoliate orange Poncirus trifoliata (L.) Raf. rootstock was divided into two segments-leaf tip and leaf center, and transmission electron microscope (TEM) and fourier transform infrared spectroscopy (FTIR) were used to obtain more detailed information on the cell ultrastructure and component architecture of the two leaf segments under B toxicity. Results revealed that B toxicity led to alterations in pectin network crosslinking structure of leaf tip and destruction of cell wall integrity. Moreover, B toxicity altered protein structure and decreased protein content, while increased carbohydrate content in the two leaf segments, especially in leaf tip. Excess B supply reduced the cellulose content in leaf tip but increased in leaf center. TEM micrographs exhibited chloroplast disintegration and plastoglobulus accumulation in cells of two different leaf sections of B-toxicity plants, with less pronounced changes in leaf center. Furthermore, B toxicity only induced accumulation of starch grains in cells of leaf center. Overall results indicated that the B-toxic-induced biochemical changes of the cell ultrastructure and component architecture greatly differed in leaf tip and center. This study facilitates a better understanding of structural changes in different leaf portions of P. trifoliata under B toxicity stress and provides new ideas for further research on other elements in different plant leaf portions.
•Structural responses of varied leaf segments differed to B toxicity.•B toxicity decreased cellulose content in leaf tip but increased it in leaf center.•Excess B induced more chloroplast disintegration and plastoglobulus accumulation in leaf tip.
The discovery of STING-related innate immunity has recently provided a deep mechanistic understanding of immunopathy. While the detrimental effects of STING during sepsis had been well documented, ...the exact mechanism by which STING causes lethal sepsis remains obscure. Through single-cell RNA sequence, genetic approaches, and mass spectrometry, we demonstrate that STING promotes sepsis-induced multiple organ injury by inducing macrophage ferroptosis in a cGAS- and interferon-independent manner. Mechanistically, Q237, E316, and S322 in the CBD domain of STING are critical binding sites for the interaction with the coiled-coil domain of NCOA4. Their interaction not only triggers ferritinophagy-mediated ferroptosis, but also maintains the stability of STING dimers leading to enhanced inflammatory response, and reduces the nuclear localization of NCOA4, which impairs the transcription factor coregulator function of NCOA4. Meanwhile, we identified HET0016 by high throughput screening, a selective 20-HETE synthase inhibitor, decreased STING-induced ferroptosis in peripheral blood mononuclear cells from patients with sepsis and mortality in septic mice model. Our findings uncover a novel mechanism by which the interaction between STING and NCOA4 regulates innate immune response and ferroptosis, which can be reversed by HET0016, providing mechanistic and promising targets insights into sepsis.
Abdominal wall defect caused by open abdomen (OA) or abdominal trauma is a serious issue since it induces several clinical problems. Although a variety of prosthetic materials are commonly employed, ...complications occur including host soft tissue response, fistula formation and chronic patient discomfort. Recently, abundant natural polymers have been used for injectable hydrogel synthesis in tissue regeneration. In this study, we produced the chitosan - hyaluronic acid (CS/HA) hydrogel and investigated its effects on abdominal tissue regeneration. The physical and biological properties of the hydrogel were demonstrated to be suitable for application in abdominal wounds. In a rat model simulating open abdomen and large abdominal wall defect, rapid cellular response, sufficient ECM deposition and marked neovascularization were found after the application of the hydrogel, compared to the control group and fibrin gel group. Further, the possible mechanism of these findings was studied. Cytokines involved in angiogenesis and cellular response were increased and the skew toward M2 macrophages credited with the functions of anti-inflammation and tissue repair was showed in CS/HA hydrogel group. These findings suggested that CS/HA hydrogel could prevent the complications and was promising for abdominal tissue regeneration.
Stimulator of interferon genes (STING) is an endoplasmic-reticulum resident protein, playing essential roles in immune responses against microbial infections. However, over-activation of STING is ...accompanied by excessive inflammation and results in various diseases, including autoinflammatory diseases and cancers. Therefore, precise regulation of STING activities is critical for adequate immune protection while limiting abnormal tissue damage. Numerous mechanisms regulate STING to maintain homeostasis, including protein-protein interaction and molecular modification. Among these, post-translational modifications (PTMs) are key to accurately orchestrating the activation and degradation of STING by temporarily changing the structure of STING. In this review, we focus on the emerging roles of PTMs that regulate activation and inhibition of STING, and provide insights into the roles of the PTMs of STING in disease pathogenesis and as potential targeted therapy.
Intestinal ischemia reperfusion (I/R) injury is the important pathogenesis for acute intestinal barrier disruption. The STING signaling is associated with gut homeostasis and barrier integrity. ...However, the biological function and regulation of STING signaling in intestinal I/R injury are not yet fully understood. As the ligand of STING signaling, the mitochondrial DNA (mtDNA) has been found to be associated with necroptosis. It still remains unknown whether mtDNA-STING signaling triggers intestinal necroptosis in intestinal I/R injury. We found that circulating RIPK3 was significantly increased and had a positive correlation with markers of enterocyte injury in critically ill patients with intestinal injury. Moreover, the levels of circulating mtDNA were also associated with the levels of circulating RIPK3. To explore the relationship between mtDNA and intestinal necroptosis, mice were treated with the intraperitoneal injection of mtDNA, and necroptosis signaling was remarkably activated and the inhibition of necroptosis alleviated mtDNA-induced intestinal injury. Furthermore, STING knockout mice showed an alleviated intestinal necroptosis. In intestinal I/R injury, mtDNA was released from IECs and necroptosis was also triggered, companied with a significant decrease of RIPK3 in the intestine. STING knockout mice markedly attenuated intestinal necroptosis and intestinal I/R injury. Finally, we found that mtDNA-mediated STING signaling triggered necroptosis through synergistic IFN and TNF-α signaling in primary IECs. Our results indicated that mtDNA-STING signaling can contribute to intestinal I/R injury by promoting IEC necroptosis. STING-mediated both IFN and TNF-α signaling can trigger intestinal nercroptosis.
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