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The addition of extracellular soluble HMGB1 protected AFG1-induced DNA damage through the TLR2/NF-κB pathway in Beas-2b cells. In addition, blockade of endogenous HMGB1 by siRNA significantly enhanced AFG1-induced damage. Thus, our findings showed that both extracellularly-released and nuclear and cytosolic HMGB1 could protect the cell from AFG1-induced cell damage in a TNF-〈-dependent lung inflammatory environment.In a recent study, Yasuda et al. show how liquid-liquid phase separation (LLPS) under hyperosmotic stress conditions allows cells to react to ubiquitinated proteins and to assemble nuclear, liquid compartments that recruit proteasomes and result in aggregate clearance.Since the outbreak of novel coronavirus pneumonia (coronavirus disease 2019, COVID-19) in December 2019, it has rapidly spread to 187 countries, causing serious harm to the health of people and a huge social burden. However, currently, drugs specifically approved for clinical use are not available, except for vaccines against COVID-19 that are being evaluated. Traditional Chinese medicine (TCM) is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients, and has a better ability of epidemic prevention and control. The authors comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM, and discussed its syndrome differentiation, treatment and prevention measures so as to provide strategies and reference for the prevention and treatment with TCM.Introduction Treatment of humeral non-union with or without bone defect is complex, with non-negligible rates of complication and failure. Few reports focused on management of treatment failure. Objective The study hypothesis was that the induced-membrane technique associated in a 2-stage strategy to internal fixation provides systematic bone healing in refractory humeral non-union. Material and methods The study included 15 patients, with a median age of 46.6 years, with humeral non-union of a mean 24 months' progression and mean history of 3 attempted revision surgeries. Seven patients showed bone defect, exceeding 5cm in 2 cases. Six had history of radial palsy. Results Consolidation was achieved in all cases, at a mean 4.6 months. Ten patients underwent radial nerve transposition, 6 of whom had shown radial motor nerve palsy; all recovered within 2 to 5 months. There was 1 case of superficial infection, and 1 of seroma. Discussion The induced-membrane technique ensures bone healing due to the biological properties of the membrane; the main drawback is the need for 2-stage surgery. When bone defect exceeds 5cm, a multi-perforated fibula segment can be placed inside the membrane to increase primary stability and enhance bone integration. Conclusion The induced-membrane technique is suited to humeral non-union, with or without bone defect. The 2-stage strategy is mandatory in case of suspected latent infection. In the 2-stage procedure, anteromedial radial nerve transposition facilitates the bone-graft stage. Level of evidence IV, retrospective study.Introduction Recurrence rates after primary traumatic shoulder dislocation are distinctly high. Whether the early external immobilization (ER) is better than the internal immobilization (IR) is still controversial. Hypothesis To perform a systematic review of randomized clinical trials (RCTs) that assessed the ability of external immobilization to reduce the recurrence in patients with primary anterior shoulder instability. Material and method As with the original review, we used the search strategies recommended by the Cochrane Back Review Group for the identification of RCTs. Thirteen RCTs were included in the systematic review, and 11 studies were included in the quantitative synthesis. Result A total of 1042 participants with primary shoulder dislocation were involved. The meta-analysis of 11 trials revealed that ER therapy leading to less recurrence rates than participants treated with IR therapy (RR=0.55; 95%CI 0.36 to 0.82; Z=2.88; p=0.004), and less complications (RR=0.6; 95%CI 0.39 to 0.92; Z=2.33; p=0.02) from the 5 independent trials. The meta-analysis of three trials revealed that there are not statistically significant in compliance rate (RR=1.08; 95%CI 0.89 to 1.29; Z=0.78; p=0.44). selleck chemical The GRADE level of evidence is high for adverse events, but moderate for recurrence rate and Compliance rate. The Begg test showed that no significant publication bias was detected (p=0.062). Discussion This meta-analysis suggests that external immobilization is recommended to reduce the recurrence rate and prevent complications. Level of proof II, low-powered systematic review and meta-analysis (systematic review, meta-analysis).The Membrane Attack Complex-Perforin (MACPF) family is ubiquitously found in all kingdoms. They have diverse cellular roles, however MACPFs with pore-forming toxic function in venoms and poisons are very rare in animals. Here we present the structure of PmPV2, a MACPF toxin from the poisonous apple snail eggs, that can affect the digestive and nervous systems of potential predators. We report the three-dimensional structure of PmPV2, at 17.2 Å resolution determined by negative-stain electron microscopy and its solution structure by small angle X-ray scattering (SAXS). We found that PV2s differ from nearly all MACPFs in two respects it is a dimer in solution and protomers combine two immune proteins into an AB toxin. The MACPF chain is linked by a single disulfide bond to a tachylectin chain, and two heterodimers are arranged head-to-tail by non-covalent forces in the native protein. MACPF domain is fused with a putative new Ct-accessory domain exclusive to invertebrates. The tachylectin is a six-bladed β-propeller, similar to animal tectonins. We experimentally validated the predicted functions of both subunits and demonstrated for the first time that PV2s are true pore-forming toxins. The tachylectin ¨B¨ delivery subunit would bind to target membranes, and then the MACPF ¨A¨ toxic subunit would disrupt lipid bilayers forming large pores altering the plasma membrane conductance. These results indicate that PV2s toxicity evolved by linking two immune proteins where their combined preexisting functions gave rise to a new toxic entity with a novel role in defense against predation. This structure is an unparalleled example of protein exaptation.