Seismic performance evaluation of precast post-tensioned high-performance concrete frame beam-column joint under cyclic loading.

Precast concrete structures have developed rapidly because they meet the requirements of green and low-carbon social development. In this paper, a precast post-tensioned high-performance concrete frame beam-column joint was proposed, and the low-cycle reversed load test was performed on the four proposed joints. The main differences between the four joints are the different prestress values applied by the joints and whether the beam-column joint is provided with L-shaped steel. The seismic performance indexes such as hysteresis curve, stiffness degradation, deformation capacity, energy dissipation capacity and residual deformation of each node were obtained through experiments. By comparing various seismic performance indicators, it could be found that the use of high-performance concrete could effectively avoid the phenomenon of local crushing of concrete due to excessive prestressing. At the same time, it was found that the setting of L-shaped steel plate at the beam-column junction could effectively avoid the early damage at the beam-column junction. On the basis of the test, the three-line restoring force model of the joint was established by the method of experimental regression analysis. The model could better reflect the stress situation of each stage of the joint. Based on the experimental and theoretical analysis, the finite element analysis model of the joint was established, and the model calculation results were in good agreement with the experimental results.

Canine interleukin-31 binds directly to OSMRß with higher binding affinity than to IL-31RA.

Interleukin-31 (IL-31) is a pro-inflammatory cytokine involved in skin inflammation and tumor progression. The IL-31 signaling cascade is initiated by its binding to two receptors, IL-31 receptor alpha (IL-31RA) and oncostatin M receptor subunit beta (OSMRß). The previous study suggested that human IL-31 (hIL-31) directly interacts with IL-31RA and OSMRß, independently, but the binding ability of hIL-31 to IL-31RA is stronger than to OSMRß. In different to its human ortholog, feline IL-31 (fIL-31) has a higher binding affinity for feline OSMRß. However, the binding pattern of canine IL-31 to its receptors remains to be elucidated. In this study, we purified the recombinant canine IL-31 (rcIL-31) protein and revealed its secondary structure to be mainly composed of alpha-helices. Moreover, in vitro studies show that rcIL-31 has the ability to induce the phosphorylation of signal transducer activator of transcription 3 (STAT3) and STAT5 in DH-82 cells. In the following, the binding efficacies of bioactive rcIL-31 for its individual receptor components have been measured using a flow cytometry assay. The result demonstrates that correctly refolded rcIL-31 binds independently with cIL-31RA and cOSMRß which were expressed on the cell surface. Of note, rcIL-31 has a greater than tenfold higher affinity to OSMRß than to IL-31RA. Additionally, we demonstrated that D1-D4, especially D4 of cOSMRß, is crucial for its binding to cIL-31. Furthermore, this study proved that rcIL-31 has a high binding affinity to the soluble cOSMRß with a KD value of 3.59 × 10-8 M. The results presented in the current study will have a significant implication in the development of drugs or antibodies against diseases induced by cIL-31 signaling.

Expression, purification, and biological characterization of recombinant human interleukin-31 protein.

Interleukin-31 (IL-31), belonging to the IL-6 cytokine family, is involved in skin inflammation and pruritus, as well as some tumors' progression. Here, we reported the expression and purification of recombinant human IL-31 (rhIL-31) using a prokaryotic system. This recombinant protein was expressed in the form of inclusion bodies, refolded and purified by size-exclusion chromatography. Circular dichroism analysis revealed that the secondary structure of rhIL-31 was mainly composed of alpha-helix, which is in consistence with the 3D model structure built by AlphaFold server. In vitro studies showed that rhIL-31 exhibited a good binding ability to the recombinant hIL-31 receptor alpha fused with human Fc fragment (rhIL-31RA-hFc) with EC50 value of 16.36 µg/mL in ELISA assay. Meanwhile, flow cytometry demonstrated that rhIL-31 was able to bind to hIL-31RA or hOSMRß expressed on the cell surface, independently. Furthermore, rhIL-31 could induce the phosphorylation of STAT3 in A549 cells. In conclusion, the prepared rhIL-31 in this study possesses the binding ability to its receptors, and can activate the signal pathway of JAK/STAT. Thus, it can be applied in further studies, including investigation of hIL-31-related diseases, structural analysis, and development of therapeutic drugs, and monoclonal antibodies targeting hIL-31.

Development and characterization of a novel mouse anti-canine oncostatin M receptor beta monoclonal antibody.

Oncostatin M receptor beta (OSMRß) mediates signaling of Oncostatin M (OSM) and interleukine-31 (IL-31), two key cytokines involved in many important biological processes including inflammation and cancer progression. More importantly, OSMRß might be a potential biomarker and therapeutic target for some diseases, such as inflammatory bowel disease, pruritus and ovarian cancer. In this study, soluble recombinant canine OSMRß (cOSMRß) was experimentally expressed as a native antigen to develop an effective cOSMRß-specific monoclonal antibody (mAb), 2O2, using hybridoma technology. It was demonstrated that 2O2 is able to detect OSMRß expressed on cell surface using immunofluorescence assay (IFA) and flow cytometry (FACS). This mAb exhibits very high binding affinity to cOSMRß with the KD and half-maximal effective concentration (EC50) values of 2.49 nM and 96.96 ng/ml, respectively. Meanwhile, it didn't show any cross-relativities with feline OSMRß (fOSMRß) and human OSMRß (hOSMRß). Moreover, we determined the binding epitope of 2O2, which localizes in the domain VI (DVI, amino acids 623-734) of cOSMRß. In conclusion, this novel mAb, 2O2, can be used in immunoassays, including IFA, FACS and enzyme-linked immunosorbent assay (ELISA) to facilitate studies in dogs.

The association of periodontal diseases and Sjogren's syndrome: A systematic review and meta-analysis.

Background: The relationship between periodontal diseases and Sjogren's syndrome were found inconsistent in current studies. Our objective is to clarify the relationship between periodontal diseases and Sjogren's syndrome. Methods: A systematic review was performed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic databases (EMBASE, PubMed, Web of Science, and Cochrane Library, from inceptions until 24 November 2021) were searched. The Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) were applied to evaluate the quality of studies. Quality assessment of the certainty of evidence was performed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. When the output is the ratio, Odds ratio (OR) of periodontal diseases with Sjogren's syndrome were calculated. When the output is the mean, weighted mean difference (WMD) of periodontal diseases with Sjogren's syndrome was calculated. We conducted meta-analysis and estimated the pool sensitivity. Begg's test was used to test the possibility of publication bias. We also carried out meta-regression to clarify the source of heterogeneity (I2 > 50%). Finally, we performed a trial sequential analysis (TSA) to identify the false positive or false negative outcomes that might occur during repeated updates. Results: 21 studies were included in this systematic review, with a total of 11435 subjects. Meta-analysis of 5 studies showed that there is a positive correlation between periodontitis and Sjogren's syndrome (OR = 2.12, 95% CI = 1.43-3.17; 5 studies, 6927 participants; low certainty of evidence). Meta-analysis of 16 studies showed that the periodontal condition of patients with Sjogren's syndrome was worse compared with the control group, and the scores of clinical periodontal parameters were relatively high. Conclusion: Sjogren's syndrome patients seem to be more likely to be diagnosed with periodontal diseases. However, our results should be interpreted with caution considering the high heterogeneity. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021261322].

Immunomodulation in the Treatment of Periodontitis: Progress and Perspectives.

Periodontitis is one of the most common dental diseases. Compared with healthy periodontal tissues, the immune microenvironment plays the key role in periodontitis by allowing the invasion of pathogens. It is possible that modulating the immune microenvironment can supplement traditional treatments and may even promote periodontal regeneration by using stem cells, bacteria, etc. New anti-inflammatory therapies can enhance the generation of a viable local immune microenvironment and promote cell homing and tissue formation, thereby achieving higher levels of immune regulation and tissue repair. We screened recent studies to summarize the advances of the immunomodulatory treatments for periodontitis in the aspects of drug therapy, microbial therapy, stem cell therapy, gene therapy and other therapies. In addition, we included the changes of immune cells and cytokines in the immune microenvironment of periodontitis in the section of drug therapy so as to make it clearer how the treatments took effects accordingly. In the future, more research needs to be done to improve immunotherapy methods and understand the risks and long-term efficacy of these methods in periodontitis.

Light chain modulates heavy chain conformation to change protection profile of monoclonal antibodies against influenza A viruses.

The isolation of human monoclonal antibodies with broadly neutralizing breadth can provide a promising countermeasure for influenza A viruses infection. Most broadly neutralizing antibodies against influenza A viruses bind to the conserved stem region or the receptor-binding cavity of hemagglutinin and the interaction is dominated by the heavy chain. The light chain, however, contributes few or no direct contacts to the antigen. Here we report an H3-clade neutralizing human monoclonal antibody, AF4H1K1, which recognizes the hemagglutinin glycoproteins of all group 2 influenza A viruses. This human monoclonal antibody has been obtained through the screening by pairing different heavy and light chains from an H7N9-infected patient based on the next-generation sequencing technology. Further structural studies revealed that light chains modulate the neutralizing spectrum by affecting the local conformation of heavy chains, instead of direct interaction with the antigen. These findings provide important clues to understand the molecular basis of light chains in antigen recognition and to explore the strategies in particular of the use of light chain modification to develop broadly protective monoclonal antibodies against influenza A viruses and other emerging viruses.

Clinical Value of Controlling Nutritional Status Score in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: The aim of present study was to assess the predictive value of the admission prognostic nutrition index (PNI), controlling nutritional status (CONUT) associated with delayed cerebral ischemia (DCI), and 3-month neurological outcomes after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The clinical data from 252 patients with aSAH were retrospectively analyzed. Receiver operating characteristic analysis was performed to assess the predictive ability of the PNI and CONUT score and identify the cutoff point. Multivariate analysis was conducted to assess the role of the PNI and CONUT score in predicting for DCI and outcomes at 3 months after aSAH treatment. RESULTS: We enrolled 252 patients with aSAH in our study. Of the 252 patients, 53 experienced DCI and 57 patients had a poor outcome. Patients with unfavorable outcomes had a lower serum albumin, lymphocyte count, total cholesterol, and PNI but a high CONUT score, Hunt-Hess grade, and aneurysm size (P < 0.05). Both the PNI and CONUT score correlated with the Hunt-Hess grade (r = -0.289 and P < 0.001; r = 0.512 and P < 0.001), modified Rankin scale score at 3 months (r = -0386 and P < 0.001; r = 0.533 and P < 0.001), aneurysm size (r = -0.219 and P < 0.001; r = 0.422 and P < 0.001). Only a CONUT score <4 (odds ratio, 0.241; 95% confidence interval, 0.071-0.842; P = 0.022) independently predicted the functional outcome status but not DCI at 3 months after aSAH. However, PNI was an unrelated factor associated with DCI and the clinical outcome. CONCLUSIONS: Our results have indicated that the CONUT score might efficiently predict for the clinical outcomes at 3 month after aSAH.

Double Lock of a Human Neutralizing and Protective Monoclonal Antibody Targeting the Yellow Fever Virus Envelope.

Yellow fever virus (YFV), a deadly human pathogen, is the prototype of the genus Flavivirus. Recently, YFV re-emerged in Africa and Brazil, leading to hundreds of deaths, with some cases imported to China. Prophylactic or therapeutic countermeasures are urgently needed. Previously, several human monoclonal antibodies against YFV were screened out by phage display. Here, we find that one of them, 5A, exhibits high neutralizing potency and good protection. Crystallographic analysis of the YFV envelope (E) protein in its pre- and post-fusion states shows conformations similar to those observed in other E proteins of flaviviruses. Furthermore, the structures of 5A in complex with the E protein in both states are resolved, revealing an invariant recognition site. Structural analysis and functional data suggest that 5A has high neutralization potency because it interferes with virus entry by preventing both virus attachment and fusion. These findings will be instrumental for immunogen or inhibitor design.

Lymphocyte-to-Monocyte Ratio Is an Independent Predictor for Neurological Deterioration and 90-Day Mortality in Spontaneous Intracerebral Hemorrhage.

BACKGROUND Lymphocyte-to-monocyte ratio (LMR) is an independent predictive factor of clinical outcome of acute ischemic stroke and cancer, but the predictive effect of LMR in spontaneous intracerebral hemorrhage (ICH) is unknown. Thus, the aim of this study was to explore the impact of peripheral LMR on the neurological deterioration (ND) during the initial week after spontaneous ICH onset, as well as 90-day mortality. MATERIAL AND METHODS The clinical data of 558 consecutive patients with ICH were retrospectively analyzed. LMR is calculated by absolute lymphocyte count divided by absolute monocyte count. RESULTS Of these patients, 166 patients experienced ND during the first week after admission and 72 patients died within 90 days. Multivariate analysis indicated that white blood cells (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), LMR were significantly associated with ND during the initial week after ICH onset and also were associated with 90-day mortality. Moreover, NLR and LMR showed a higher predictive ability in ND during the initial week after ICH onset than 90-day mortality in receiver operating characteristic analysis. The best cut-off points of NLR and LMR in predicting ND and 90-day mortality were 10.24 and 2.21 and 16.81 and 2.19, respectively. CONCLUSIONS Our results suggest that LMR on admission is a predictive factor for ND during the initial week after ICH onset, as well as 90-day mortality.

Insights into TIM-barrel prenyl transferase mechanisms: crystal structures of PcrB from Bacillus subtilis and Staphylococcus aureus.

Well structured: As a new triose phosphate isomerase (TIM) barrel-fold prenyl transferase, PcrB catalyzes the production of heptaprenylglyceryl phosphate from heptaprenyl diphosphate and glycerol-1-phosphate. Crystal structures of PcrB from Bacillus subtilis and Staphylococcus aureus in complex with ligands were solved, and together with site-directed mutagenesis and bioinformatics analyses, clearly reveal the catalytic mechanism of the enzyme.

The substrate/product-binding modes of a novel GH120 ß-xylosidase (XylC) from Thermoanaerobacterium saccharolyticum JW/SL-YS485.

Xylan-1,4-ß-xylosidase (ß-xylosidase) hydrolyses xylo-oligomers at their non-reducing ends into individual xylose units. Recently, XylC, a ß-xylosidase from Thermoanaerobacterium saccharolyticum JW/SL-YS485, was found to be structurally different from corresponding glycosyl hydrolases in the CAZy database (http://www.cazy.org/), and was subsequently classified as the first member of a novel family of glycoside hydrolases (GH120). In the present paper, we report three crystal structures of XylC in complex with Tris, xylobiose and xylose at 1.48-2.05 Å (1 Å=0.1 nm) resolution. XylC assembles into a tetramer, and each monomer comprises two distinct domains. The core domain is a right-handed parallel ß-helix (residues 1-75 and 201-638) and the flanking region (residues 76-200) folds into a ß-sandwich domain. The enzyme contains an open carbohydrate-binding cleft, allowing accommodation of longer xylo-oligosaccharides. On the basis of the crystal structures and in agreement with previous kinetic data, we propose that XylC cleaves the glycosidic bond by the retaining mechanism using two acidic residues Asp382 (nucleophile) and Glu405 (general acid/base). In addition to the active site, nine other xylose-binding sites were consistently observed in each of the four monomers, providing a possible reason for the high tolerance of product inhibition.