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Taking RV-40E reducer as the object，the dynamic characteristics of RV reducer under free mode are studied by combining modal simulation and modal analysis experiment. Firstly，the RV reducer is modeled and simulated based on Ansys，and the simulation results of natural frequency and mode shape are obtained. After comparing the experimental modalities of the domestic and Nabtesco RV-40E reducer，the test results show that the first-order modal of domestic RV-40E reducer is generally lower than that of Nabtesco，with a maximum difference of 11.1%. At the same time，the simulation and experimental results are compared. The largest domestic difference in the first-order mode is -5.8%，and that of Nabtesco is +5.9%. The above research provides effective data and methods for the structural optimization design and modal performance analysis of the RV reducer.

Abstract Background Neuroinflammation is a vital pathogenic mechanism for neurodegenerative diseases such as Alzheimer’s, schizophrenia, and age-related cognitive decline. Regulatory T cells (Tregs) exhibit potent anti-inflammatory properties and can modulate neurodegenerative diseases arising from central nervous system inflammatory responses. However, the role of Tregs in neuroinflammation-related cognitive dysfunction remains unclear. It is highly plausible that Htr7+ Tregs expressing unique genes associated with the nervous system, including the Htr7 gene encoding the serotonin receptor 5-HT7, play a pivotal role. Methods Mice were given a tryptophan-rich diet (with a tryptophan content of 0.6%) or a normal diet (with a tryptophan content of 0.16%). The neuroinflammation-mediated cognitive dysfunction model was established by intracerebroventricular injection of lipopolysaccharide (LPS) in 8-week-old C57BL/6J mice. The activation and infiltration of Tregs were measured using flow cytometry. Primary Tregs were cocultured separately with primary CD8+ T cells and primary microglia for in vitro validation of the impact of 5-HT and 5-HT7 receptor on Tregs. Prior to their transfer into recombination activating gene 1 (Rag1−/−) mice, Tregs were ex vivo transfected with lentivirus to knock down the expression of Htr7. Results In this study, the tryptophan-rich diet was found to reverse LPS-induced cognitive impairment and reduce the levels of 5-HT in peripheral blood. The tryptophan-rich diet led to increased levels of 5-HT in peripheral blood, which in turn promoted the proliferation and activation of Htr7+ Tregs. Additionally, the tryptophan-rich diet was also shown to attenuate LPS-mediated neuroinflammation by activating Htr7+ Tregs. Furthermore, 5-HT and 5-HT7 receptor were found to enhance the immunosuppressive effect of Tregs on CD8+ T cells and microglia. In Rag1−/− mice, Htr7+ Tregs were shown to alleviate LPS-induced neuroinflammation and cognitive impairment. Conclusions Our research revealed the ability of Htr7+ Tregs to mitigate neuroinflammation and prevent neuronal damage by suppressing the infiltration of CD8+ T cells into the brain and excessive activation of microglia, thereby ameliorating LPS-induced cognitive impairment. These insights may offer novel therapeutic targets involving Tregs for neuroinflammation and cognitive impairment.

Abstract Background In on-pump cardiac surgery, the albumin priming strategy could maintain colloid osmotic pressure better than crystalloid solutions and reduce excessive perioperative fluid balance. However, a high-quality meta-analysis is required to compare the safety of these approaches in perioperative red blood cell (RBC) transfusions. Owing to limited direct evidence, we conducted a network meta-analysis (NMA) to increase the pool of studies and provide indirect evidence. Methods The pre-defined primary outcomes were intraoperative and the first 24 h postoperative RBC transfusion volume in units. The pre-defined secondary outcome was postoperative blood loss (the first 24 h). We reviewed all randomized controlled trials comparing albumin, crystalloid, and artificial colloid priming strategies. Studies that only displayed pre-defined outcomes could be included. A pairwise meta-analysis was performed on studies that directly compared the pre-defined outcomes between albumin and crystalloids. Additionally, a random-effects network meta-analysis (NMA) model was employed to generate indirect evidence for the pre-defined outcomes between albumin and crystalloids. Results The literature search identified 830 studies,10 of which were included in the final analysis. Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative RBC transfusions (MD: -0.68U; 95%CI: -1.26, -0.09U; P = 0.02) and intraoperative RBC transfusions (MD: -0.20U; 95%CI: -0.39, -0.01U; P = 0.03) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant. (MD: -0.16U; 95%CI: -0.45, 0.14U; P = 0.30). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance. For postoperative blood loss, direct evidence showed no significant differences between albumin and crystalloid priming strategies. However, NMA evidence displayed that albumin exist higher probability of reducing postoperative blood loss than crystalloid. Conclusion Both direct and NMA evidence indicated that the albumin priming strategy resulted in more perioperative RBC transfusions than crystalloids. Considering the additional blood management burden, the application of an albumin-priming strategy in on-pump cardiac surgery still needs more consideration.

Inflammation is a defensive response of the body to various inflammatory factors and injuries, and it is also a key factor in the occurrence of many chronic diseases. The research shows that oligosaccharides have many physiological activities, such as anti-inflammation, anti-biosis, anti-oxidation and anti-cancer. As a new type of functional sugar source, oligosaccharides have the characteristics of low calories, high solubility and promotion of bifidobacterial proliferation. In this article, the types and preparation methods of oligosaccharides with anti-inflammatory activity in recent years are introduced, and the anti-inflammatory mechanisms are reviewed from two aspects of inflammatory mediators and inflammatory signaling pathways, in order to provide the reference for the development of new anti-inflammatory drugs.

Abstract Herein, an unprecedented synergistic strategy for the development of high-performance NIR-II fluorophore is proposed and validated. Based on an unsymmetrical cyanine dye design strategy, the NIR-II emissive dye NIC was successfully developed by replacing only one of the indoline donors of symmetrical cyanine dye ICG with a fully conjugated benz[c,d]indole donor. This minor structural change maximally maintains the high extinction coefficient advantage of cyanine dyes. NIC-ER with endogenous albumin-hitchhiking capability was constructed to further enhance its in vivo fluorescence brightness. In the presence of HSA (Human serum albumin), NIC-ER spontaneously resides in the albumin pocket, and a brilliant ~89-fold increase in fluorescence was observed. Due to its high molar absorptivity and moderate quantum yield, NIC-ER in HSA exhibits bright NIR-II emission with high photostability and significant Stokes shift (>110 nm). Moreover, NIC-ER was successfully employed for tumor-targeted NIR-II/PA imaging and efficient photothermal tumor elimination. Overall, our strategy may open up a new avenue for designing and constructing high-performance NIR-II fluorophores.

Abstracts Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C max and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

PurposeTo synthesize the dimer of GX1 and identify whether its affinity and targeting are better than those of GX1. To prepare 68Ga-DOTA-KEK-(GX1)2 and to apply it to PET and Cerenkov imaging of gastric cancer.Methods68Ga-DOTA-KEK-(GX1)2 was prepared, and the labeling yield and stability were determined. Its specificity and affinity were verified using an in vitro cell binding assay and competitive inhibition test, cell immunofluorescence, and cell uptake and efflux study. Its tumor-targeting ability was determined by nano PET/CT and Cerenkov imaging, standardized uptake value (SUV), signal-to-background ratio (SBR) quantification, and a biodistribution study in tumor-bearing nude mice.Results68Ga-DOTA-KEK-(GX1)2 was successfully prepared, and the labeling yield was more than 97%. It existed stably for 90 min in serum. The binding of 68Ga-DOTA-KEK-(GX1)2 to cocultured HUVECs (Co-HUVECs) was higher than that to human umbilical vein endothelial cells (HUVECs), BGC823 cells, and GES cells. It was also higher than that of 68Ga-DOTA-GX1, indicating that the dimer did improve the specificity and affinity of GX1. The binding of KEK-(GX1)2 to Co-HUVECs was significantly higher than that of GX1. Additionally, the uptake of 68Ga-DOTA-KEK-(GX1)2 by Co-HUVECs was higher than that of 68Ga-DOTA-GX1 and reached a maximum at 60 min. Nano PET/CT and Cerenkov imaging showed that the tumor imaging of the nude mice injected with 68Ga-DOTA-KEK-(GX1)2 was clear, and the SUV and SBR value of the tumor sites were significantly higher than those of the nude mice injected with 68Ga-DOTA-GX1, indicating that the probe had better targeting in vivo. Finally, the biodistribution showed quantitatively that when organs such as the kidney and liver metabolized rapidly, the radioactivity of the tumor site of the nude mice injected with 68Ga-DOTA-KEK-(GX1)2 decreased relatively slowly. At the same time, the percentage of injected dose per gram (%ID/g) of the tumor site was higher than that of other normal organs except the liver and kidney at 60 min, which indicated that the tumor had good absorption of the probe.ConclusionGX1 was modified successfully, and the in vivo and in vitro properties of the GX1 dimer were significantly better than those of GX1. The imaging probe, 68Ga-DOTA-KEK-(GX1)2, was successfully prepared, which provides a candidate probe for PET and Cerenkov diagnosis of gastric cancer.

Cloud segmentation is a fundamental step in accurately acquiring cloud cover. However, due to the nonrigid structures of clouds, traditional cloud segmentation methods perform worse than expected. In this paper, a novel deep convolutional neural network (CNN) named MA-SegCloud is proposed for segmenting cloud images based on a multibranch asymmetric convolution module (MACM) and an attention mechanism. The MACM is composed of asymmetric convolution, depth-separable convolution, and a squeeze-and-excitation module (SEM). The MACM not only enables the network to capture more contextual information in a larger area but can also adaptively adjust the feature channel weights. The attention mechanisms SEM and convolutional block attention module (CBAM) in the network can strengthen useful features for cloud image segmentation. As a result, MA-SegCloud achieves a 96.9% accuracy, 97.0% precision, 97.0% recall, 97.0% F-score, 3.1% error rate, and 94.0% mean intersection-over-union (MIoU) on the Singapore Whole-sky Nychthemeron Image Segmentation (SWINySEG) dataset. Extensive evaluations demonstrate that MA-SegCloud performs favorably against state-of-the-art cloud image segmentation methods.

In this paper, the wear property of ER8 and SSW-Q3R wheel steel under pure rolling condition was studied by GMP-30 wear tester. The results showed that the wear loss of the ER8 wheel steel was higher than that of the SSW-Q3R wheel steel at the same cycles. The high carbon content of the SSW-Q3R improved the surface hardness during rolling wear. The high hardness increased the wear resistance of the SSW-Q3R wheel steel. During rolling wear, the fatigue wear resistance of ER8 wheel was worse than that of the SSW-Q3R wheel steel due to more proeutectoid ferrite content in ER8 wheel steel. The surface residual stress of ER8 and SSW-Q3R wheel steel increased with the increase in cycles. The axial residual compressive stress on the surface of the sample was greater than the circumferential residual compressive stress. The residual stress at the trough was higher than that at the crest.