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Abstract The maintenance of hematopoietic stem cell (HSC) functional integrity is essential for effective hematopoietic regeneration when suffering from injuries. Studies have shown that the innate immune pathways play crucial roles in the stress response of HSCs, whereas how to precisely modulate these pathways is not well characterized. Here, we identify the E3 ubiquitin ligase tripartite motif-containing 47 (Trim47) as a negative regulator of the mitochondrial antiviral-signaling protein (MAVS)-mediated innate immune pathway in HSCs. We find that Trim47 is predominantly enriched in HSCs, and its deficiency impairs the function and survival of HSCs after exposure to 5-flurouracil (5-FU) and irradiation (IR). Mechanistically, Trim47 impedes the excessive activation of the innate immune signaling and inflammatory response via K48-linked ubiquitination and degradation of MAVS. Collectively, our findings demonstrate a role of Trim47 in preventing stress-induced hematopoietic failure and thus provide a promising avenue for treatment of related diseases in the clinic.

The hematopoietic system is susceptible to ionizing radiation (IR), which can cause acute hematopoietic failure or long-term myelosuppression. As the most primitive cells of the hematopoietic hierarchy, hematopoietic stem cells (HSCs) maintain lifelong hematopoietic homeostasis and promote hematopoietic regeneration during stress. Numerous studies have shown that nuclear and mitochondrial genomes are the main targets of radiation injury in HSCs. More importantly, the damage of DNA may trigger a series of biological responses that largely determine HSC fate following IR exposure. Although some essential pathways and factors involved in DNA injury and damage in HSCs have been revealed, a comprehensive understanding of the biological effects of radiation on HSCs still needs to be improved. This review focuses on recent insights into the molecular mechanisms underlying DNA damage and repair in HSCs after IR. Then summarize corresponding regulatory measures, which may provide a reference for further research in this field.

The degradation behavior and the decay of the mechanical performance of Zn-0.45Mn and Zn-0.45Mn-0.4Li alloys in simulated intestinal fluid (SIF) were investigated. The Zn-0.45Mn-0.4Li alloy, which was made of Zn phase, MnZn13 phase, and LiZn4 phase with the addition of Li element, degraded more quickly than the Zn-0.45Mn alloy. The two Zn alloys in SIF had comparable corrosion models, and the corrosion products fell off periodically. With an elongation (EL) of 57.8% and an ultimate tensile strength (UTS) of 391 MPa, Zn-0.45Mn-0.4Li had outstanding mechanical properties compared with Zn-0.45Mn. The LiZn4 phase that formed in the Zn-0.45Mn-0.4Li alloy as a result of the inclusion of Li element had a pinning effect that increased the alloy strength. When the Zn alloys were submerged in SIF, their EL gradually reduced as the immersing duration increased, but their UTS stayed mostly constant. Zn-0.45Mn-0.4Li had 396 MPa UTS and 29.7% EL after 90 days of immersion. Cytotoxicity test proved that Zn-0.45Mn-0.4Li had excellent biocompatibility. Zn–Mn–Li alloys had promising potential for gastrointestinal anastomosis.

Abstract Cancers of the same tissue-type but in anatomically distinct locations exhibit different molecular dependencies for tumorigenesis. Proximal and distal colon cancers exemplify such characteristics, with BRAF V600E predominantly occurring in proximal colon cancers along with increased DNA methylation phenotype. Using mouse colon organoids, here we show that proximal and distal colon stem cells have distinct transcriptional programs that regulate stemness and differentiation. We identify that the homeobox transcription factor, CDX2, which is silenced by DNA methylation in proximal colon cancers, is a key mediator of the differential transcriptional programs. Cdx2-mediated proximal colon-specific transcriptional program concurrently is tumor suppressive, and Cdx2 loss sufficiently creates permissive state for BRAF V600E -driven transformation. Human proximal colon cancers with CDX2 downregulation showed similar transcriptional program as in mouse proximal organoids with Cdx2 loss. Developmental transcription factors, such as CDX2, are thus critical in maintaining tissue-location specific transcriptional programs that create tissue-type origin specific dependencies for tumor development.

MET exon 14 (METex14) skipping is the most reported MET mutation in non-small cell lung cancer (NSCLC) and has been confirmed to respond to MET tyrosine kinase inhibitors (TKI) in clinical trials. While MET TKI tepotinib was recently approved for METex14 skipping NSCLC in China, real-world evidence is limited. We report our experience treating NSCLC patients referred from oncology sites across China with tepotinib in the Boao Lecheng Pilot Zone. Four patients have been prescribed the drug with a median age of 67 years (range, 61–71 years). One patient has concomitant BRAF V600E mutation, and another patient had savolitinib as first line of therapy but discontinued due to hepatotoxicity. Till the end of follow-up, four patients were all on tepotinib therapy, with a median duration of therapy of 19 months. One patient achieved partial response and three achieved stable disease. Three patients had peripheral edema, but all were mild. Our experience showed in real clinical setting, tepotinib had robust and durable clinical activity and a favorable toxicity profile in Chinese patients with METex14 skipping NSCLC. It is the first report on the effectiveness of tepotinib in a patient with both METex14 skipping and BRAF V600E mutations and successful MET inhibitor switch after MET inhibitor-induced liver injury.

A novel Fe2+/Tyr/H2O2 fluorescence reaction system has been established for the purpose of analyzing glucose oxidase activity. This system involves the catalysis of glucose oxidase on glucose to produce H2O2, which in turn oxidizes tyrosine to a highly fluorescent substance under the catalysis of Fe2+. The fluorescence intensity is subsequently employed to ascertain the enzymatic activity of glucose oxidase. The enzymatic oxidation reaction and tyrosine fluorescence reaction conditions were optimized based on the H2O2 standard curve equation. Direct fluorescence spectrophotometry was used to determine the activity range and detection limit of glucose oxidase, which were found to be 7.00 × 10−5–7.00 × 10−2 U/mL and 3.36 × 10−5 U/mL (Enzyme-like activity is 6.72 × 10−4 U/mL, The enzyme reaction time is 5 min), respectively, with a relative standard deviation of less than 3.2 %. This method has been successfully applied to determine the activity of glucose oxidase in food additives, with a recovery rate ranging from 96.00 % to 102.0 %.

With the continuous integration of semiconductor devices, the requirements of the size accuracy and surface quality of etched lead frames are stricter. The etchant is a key factor in the etching process and etched surface quality, while the effects of the difference in etchants on the etched surface morphology of Cu alloy have not been directly studied. In this study, aqua regia, acidic FeCl3 and two CuCl2 solutions were used as etchants, and different CuCrSn specimens were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocations have significant influences on the local etching rate. The preferential etching of some atomic planes forms steps between the grains with different orientations, and preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For the surfaces etched by the FeCl3 and CuCl2 etchants, the steps and grooves are blurred; thus, they are less rough. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high-density Cr-rich particles remain on the surfaces etched by the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism, rate and the etched surface morphology.

The effect of extrusion on the microstructure, mechanical property, corrosion behavior, and in vitro biocompatibility of as-cast Mg-1.5Zn-1.2Y-0.1Sr (wt.%) alloy was investigated via tensile tests, electrochemical methods, immersion tests, methylthiazolyl diphenyltetrazolium bromide (MTT), and analytical techniques. Results showed that the as-cast and as-extruded Mg-1.5Zn-1.2Y-0.1Sr alloys comprised an α-Mg matrix and Mg3Y2Zn3 phase (W-phase). In the as-cast alloy, the W-phase was mainly distributed at the grain boundaries, with a small amount of W-phase in the grains. After hot extrusion, the W-phase was broken down into small particles that were dispersed in the alloy, and the grains were refined considerably. The as-extruded alloy exhibited appropriate mechanical properties that were attributed to refinement strengthening, dispersion strengthening, dislocation strengthening, and precipitation strengthening. The as-cast and as-extruded alloys exhibited galvanic corrosion between the W-phase and α-Mg matrix as the main corrosion mechanism. The coarse W-phase directly caused the poor corrosion resistance of the as-cast alloy. The as-extruded alloy obtained via hydrogen evolution and mass loss had corrosion rates of less than 0.5 mm/year. MTT, high-content screening (HCS) analysis, and cell adhesion tests revealed that the as-extruded alloy can improve L929 cell viability and has great potential in the field of biomedical biodegradable implant materials.

BackgroundDermatomyositis (DM) is an autoimmune and inflammatory disease that can affect the lungs, causing interstitial lung diseases (ILD). However, the exact pathophysiological mechanisms underlying DM-ILD are unknown. Idiopathic pulmonary fibrosis (IPF) belongs to the broader spectrum of ILD and evidence shows that common pathologic pathways might lie between IPF and DM-ILD.MethodsWe retrieved gene expression profiles of DM and IPF from the Gene Expression Omnibus (GEO) and utilized weighted gene co-expression network analysis (WGCNA) to reveal their co-expression modules. We then performed a differentially expressed gene (DEG) analysis to identify common DEGs. Enrichment analyses were employed to uncover the hidden biological pathways. Additionally, we conducted protein-protein interaction (PPI) networks analysis, cluster analysis, and successfully found the hub genes, whose levels were further validated in DM-ILD patients. We also examined the relationship between hub genes and immune cell abundance in DM and IPF. Finally, we conducted a common transcription factors (TFs)-genes network by NetworkAnalyst.ResultsWGCNA revealed 258 intersecting genes, while DEG analysis identified 66 shared genes in DM and IPF. All of these genes were closely related to extracellular matrix and structure, cell-substrate adhesion, and collagen metabolism. Four hub genes (POSTN, THBS2, COL6A1, and LOXL1) were derived through intersecting the top 30 genes of the WGCNA and DEG sets. They were validated as active transcripts and showed diagnostic values for DM and IPF. However, ssGSEA revealed distinct infiltration patterns in DM and IPF. These four genes all showed a positive correlation with immune cells abundance in DM, but not in IPF. Finally, we identified one possible key transcription factor, MYC, that interact with all four hub genes.ConclusionThrough bioinformatics analysis, we identified common hub genes and shared molecular pathways underlying DM and IPF, which provides valuable insights into the intricate mechanisms of these diseases and offers potential targets for diagnostic and therapeutic interventions.

The purpose of this research is to conduct an exploratory study examining factors that influence the academic success of college athletes participating in the National Association of Intercollegiate Athletics (NAIA), a subject that has not been empirically studied. For this study, academic success defined as retention and graduation, represents the dependent variables of interest. Additionally, this study examines actors influencing academic success including institutional financial aid, background characteristics (race, gender), college experience (GPA, residential housing), athletic characteristics (sport, athletic expenses), organizational structure, and participation as a varsity or non-varsity athlete. This study uses institutional data from 2019-2020 NAIA’s Return on Athletics (ROA) initiative, and data from the Integrated Postsecondary Education Data System (IPEDS). Logistic regression is used to answer two research questions exploring the factors that influence NAIA college athlete success. Findings indicate athletes are retained at a high rate in comparison to available NAIA data, but certain sub-groups may be at risk for attrition. Specifically, non-varsity athletes, athletes with a grade point average below 3.0, or those who have been enrolled less than two years.

The brachial cleft carcinoma is an extremely rare head and neck facial malignancy, and there is some disagreement about its differential diagnosis. In this paper, we report a 63-year-old male patient who had a mass on the left side of the neck and diagnosed as the brachial cleft carcinoma by intraoperative biopsy pathology. However, this patient was diagnosed with the carcinoma of the left soft palate more than 20 days after surgery and esophageal cancer 2 years later, and was treated accordingly. Therefore, it is hard to confirm whether the branchial cleft carcinoma is primary or metastatic. In fact, the diagnostic criteria for primary squamous cell carcinoma of branchial cleft cysts are very rigorous. Confirmation of the diagnosis is based on pathological examination of the branchial cleft cyst epithelium lined with squamous cells, meanwhile, a thorough examination should also be performed to exclude the presence of other primary cancers.

Traditional noninvasive blood pressure measurement methods in experimental animals are time consuming and difficult to operate, particularly for large numbers of animals. In this study, the possibility of sensing fecal odor to estimate the blood pressure status of spontaneous hypertension rats (SHRs) was explored with the aim of establishing a new method for non-invasive monitoring of blood pressure. The body weight and blood pressure of SHRs kept increasing with growth, and the odor information monitored using an E-nose varied with the blood pressure status, particularly for sensors S6 and S7. The fecal information was analyzed using principal component analysis, canonical discriminant analysis and multilayer perception neural networks (MLP) to discriminate SHRs from normal ones, with a 100% correct classification rate. For better prediction of blood pressure, the model built using multiple linear regression analysis, partial least squares regression analysis and multilayer perceptron neural network analysis were used, with coefficients of determination (R2) ranging from 0.8036 to 0.9926. Moreover, the best prediction model for blood pressure was established using MLP analysis with an R2¬ higher than 0.91. Thus, changes in blood pressure levels can be tracked non-invasively, and normotension can be distinguished from hypertension or even at different hypertension levels based on the odor information of rat feces, providing a foundation for non-invasive health monitoring. This work might provide potential instructions for functional food research aimed at lowering blood pressure.

Artificial floating reefs are an important supplement to bottom reefs in marine habitat construction, which provide a good environment for fish to survive, breed and habituate in the middle and upper layers of water. They can adapt to the silt bottom of the East China Sea. To make full use of the water space and improve the effective space of the floating reef, based on the field tidal current data, an upper- and lower-layered artificial floating reef has been designed in this study. The connection method of the upper and lower reefs has been described in detail and a hydrodynamic numerical model has been established. At the same time, the effects of floating reef structure ratio, wave height and wave steepness on its force and motion are discussed under the action of tidal current and wave current. The result shows that, at a specific flow rate, the change of the proportion of the layered floating reef structure had little effect on the roll of the upper and lower reefs. The maximum roll angle does not exceed 15°, and the tilt angle of the upper and lower reefs is consistent, which ensures the good flow resistance and stability of the floating reef. Under the specific length of the connecting cable and the main mooring, the hydrodynamic characteristics of the layered floating reef are better when the ratio of the sum height of the lower reef and the connecting cable to the height of the upper reef is not greater than one and the extreme proportion structure is not considered. The tension of the stratified floating reef is proportional to the wave height and wave steepness under the action of wave and current. The main mooring rope is the most stressed, and the rolling motion of the upper and lower reefs is consistent. Above all, results can provide a theoretical basis for the optimization design of the artificial floating reef structure.

Abstract Background Evidence for peritoneal dialysis catheter (PDC) usage in pediatric patients undergoing surgery for deteriorating cardiac dysfunction is lacking. This investigation explored factors associated with PDC usage and its effectiveness in children with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Methods Eighty-four children undergoing left coronary artery transfer were retrospectively recruited. The primary endpoint was the postoperative ratio of the general ward/[intensive care unit (ICU)] length of stay. Univariable and multivariable analyses were fitted to assess factors related most strongly to PDC and the ratio of general ward/ICU length of stay. Results Of the 84 patients, 17 (20.2%) underwent postoperative PDC placement. Patients with extreme cardiac dysfunction [left ventricular ejection fraction (LVEF) ≤25%] were much more likely to require a PDC (OR, 9.88; 95% CI, 2.13–45.76; P = 0.003). Moreover, univariate analysis indicated that concomitant mitral repair significantly decreased the likelihood of PDC placement (OR, 0.25; 95% CI, 0.07–0.85; P = 0.026). In those with cardiac dysfunction (LVEF ≤50%), PDC use was associated with a reduced ratio of ward/ICU length of stay (B, − 1.62; 95% CI, − 2.77– -0.46; P = 0.008), as was age ≤ 12 months (B, − 1.57; 95% CI, − 2.88– -0.26; P = 0.02). At the 1-year follow-up, cardiac improvement was significantly greater in patients with PDC usage than in those without it (P

Abstract Background Mortality and complications remain high after acute type A aortic dissection (ATAAD) open surgery and are associated with coagulation dysfunction. Platelets play an important role in the process of coagulation. This study explored the relationship between postoperative platelet counts and 3-year mortality after operation in patients with ATAAD undergoing open aortic repair surgery. Methods Patients with ATAAD who underwent Total Arch Replacement and Frozen Elephant Trunk in Fuwai Hospital from 2011 to 2015 were selected for this study. The perioperative data were collected and sorted through the electronic clinical case system. Multivariate Logistic regression was used to analyze the risk factors for death within three years after surgery. Results A total of 495 patients were included in the analysis. After correction for confounding factors, decreased postoperative platelet count remained an independent factor that was associated with lower mortality (OR = 0.918, 95% CI 0.853–0.988, P = 0.023). Conclusions The study indicated that decreased postoperative platelet count may lead to increased 3-year mortality, in patients with ATAAD who underwent open aortic repair surgery.

Psoriasis is a chronic inflammatory skin disease that features localized or widespread erythema, papules, and scaling. It is common worldwide and may be distributed throughout the whole body. The pathogenesis of psoriasis is quite complex and the result of the interplay of genetic, environmental and immune factors. Ferroptosis is an iron-dependent programmed death that is different from cell senescence, apoptosis, pyroptosis and other forms of cell death. Ferroptosis involves three core metabolites, iron, lipids, and reactive oxygen species (ROS), and it is primarily driven by lipid peroxidation. Ferrostatin-1 (Fer-1) is an effective inhibitor of lipid peroxidation that inhibited the changes related to ferroptosis in erastin-treated keratinocytes and blocked inflammatory responses. Therefore, it has a certain effect on the treatment of psoriatic lesions. Although ferroptosis is closely associated with a variety of human diseases, such as inflammatory diseases, no review has focused on ferroptosis in psoriasis. This mini review primarily focused on the pathogenesis of psoriasis, the mechanisms of ferroptosis, the connection between ferroptosis and psoriasis and ferroptosis inhibitors in psoriasis treatment. We discussed recent research advances and perspectives on the relationship between ferroptosis and psoriasis.

We use three analytic steps to examine public investment in short-cycle tertiary education. First, reviewing the historical development, the literature reveals that national and regional policies on educational development emphasized bachelor’s programs in vocational education in the early twenty-first century, especially in the EU. This historical background informs the longitudinal trend analysis in the second step of the educational and public investment variables (2000–2018) in our econometric analysis. The combined descriptive studies illuminate competitive advantages for EU and ASEAN nations in networks emphasizing open economic and academic exchange. Third, the fixed-effects analysis indicates a higher level of investment in general tertiary education per student, associated with a lower enrollment level in short-cycle vocational and technical tertiary programs. Using insights from this three-step process, we explore the implications of a nation’s capacity to invest in short-cycle tertiary programs as part of economic development and the pursuit of social equity within and across countries. Specifically, we conclude that short-cycle programs are a step toward integrating vocational education into programs in polytechnics and other higher education institutions.

IntroductionWhile tranexamic acid (TXA) is widely used in patients with acute type A aortic dissection (ATAAD) who undergo surgical repair to reduce blood loss and transfusion requirement, the optimal dosage of TXA is unknown in these patients.Materials and MethodsThis was a retrospective cohort study that compared high-dose (>50 mg/kg) and low-dose TXA (≤50 mg/kg) in patients with ATAAD who underwent surgical repair. Propensity score matching (PSM) was performed between the two groups and results were analyzed in matched cases. The primary outcome was postoperative blood loss within 3 days after surgery. The secondary outcomes were total blood loss after surgery and perioperative blood transfusion, and safety outcomes were also assessed.ResultsThrough medical record screening, 529 patients were identified. After PSM, 196 patients in the high-dose group and 196 patients in the low-dose group were matched and included in the final analysis. Postoperative blood loss in 3 days after surgery was 940 mL (710–1,010 mL) in the low-dose group and 695 mL (620–860 mL) in the high-dose group. The difference was statistically significant (P

The 5-aminolevulinic acid (ALA), a new type of plant growth regulator, can relieve the toxicity of cadmium (Cd) to plants. However, its mechanism has not been thoroughly studied. In the study, the roles of ALA have been investigated in the tolerance of Chinese cabbage (Brassica pekinensis L.) seedlings to Cd stress. The results showed that Cd significantly reduced the biomass and the length of the primary root of seedlings but increased the malondialdehyde (MDA) and the hydrogen peroxide (H2O2) contents. These can be effectively mitigated through the application of ALA. The ALA can further induce the activities of antioxidant enzymes in the ascorbate-glutathione (AsA-GSH) cycle under Cd stress, which resulted in high levels of both GSH and AsA. Under ALA + Cd treatment, the seedlings showed a higher chlorophyll content and photosynthetic performance in comparison with Cd treatment alone. Microscopic analysis results confirmed that ALA can protect the cell structure of shoots and roots, i.e., stabilizing the morphological structure of chloroplasts in leaf mesophyll cells. The qRT-PCR results further reported that ALA downregulated the expressions of Cd absorption and transport-related genes in shoots (HMA2 and HMA4) and roots (IRT1, IRT2, Nramp1, and Nramp3), which resulted in the low Cd content in the shoots and roots of cabbage seedlings. Taken together, the exogenous application of ALA alleviates Cd stress through maintaining redox homeostasis, protecting the photosynthetic system, and regulating the expression of Cd transport-related genes in Chinese cabbage seedlings.

The use of zinc (Zn) alloys as a biodegradable metal for medical purposes has been a popular research topic. This study investigated the strengthening mechanism of Zn alloys to enhance their mechanical properties. Three Zn-0.45Li (wt.%) alloys with different deformation amounts were prepared by rotary forging deformation. Their mechanical properties and microstructures were tested. A simultaneous increase in strength and ductility was observed in the Zn-0.45Li alloys. Grain refinement occurred when the rotary forging deformation reached 75.7%. The surface average grain size reached 1.19 ± 0.31 μm, and the grain size was uniformly distributed. Meanwhile, the maximum elongation of the deformed Zn-0.45Li was 139.2 ± 18.6%, and the ultimate tensile strength reached 426.1 ± 4.7 MPa. In situ tensile tests showed that the reinforced alloys still broke from the grain boundary. Continuous and discontinuous dynamic recrystallization during severe plastic deformation produced many recrystallized grains. During deformation, the dislocation density of the alloy first increased and then decreased, and the texture strength of the (0001) direction increased with deformation. Analysis of the mechanism of alloy strengthening showed that the strength and plasticity enhancement of Zn-Li alloys after macro deformation was a combination of dislocation strengthening, weave strengthening, and grain refinement rather than only fine-grain strengthening as observed in conventional macro-deformed Zn alloys.

The effect of magnesium (Mg) content on the microstructure, mechanical properties, and cytocompatibility of degradable Zn-0.5Mn-xMg (x = 0.05 wt%, 0.2 wt%, 0.5 wt%) alloys was investigated. The microstructure, corrosion products, mechanical properties, and corrosion properties of the three alloys were then thoroughly characterized by scanning electron microscopy (SEM), electron back-scattered diffraction (EBSD), and other methods. According to the findings, the grain size of matrix was refined by the addition of Mg, while the size and quantity of Mg2Zn11 phase was increased. The Mg content could significantly improve the ultimate tensile strength (UTS) of the alloy. Compared with the Zn-0.5Mn alloy, the UTS of Zn-0.5Mn-xMg alloy was increased significantly. Zn-0.5Mn-0.5Mg exhibited the highest UTS (369.6 MPa). The strength of the alloy was influenced by the average grain size, the solid solubility of Mg, and the quantity of Mg2Zn11 phase. The increase in the quantity and size of Mg2Zn11 phase was the main reason for the transition from ductile fracture to cleavage fracture. Moreover, Zn-0.5Mn-0.2Mg alloy showed the best cytocompatibility to L-929 cells.

Purpose: Total body irradiation (TBI) has been widely utilized as part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT), but is associated with significant toxicities. Targeted TBI using helical Tomotherapy allows precise and homogeneous tumor coverage and excellent sparing of organs at risk. The purpose of this study was to evaluate the clinical outcomes of a novel hypo-fractionation strategy for patients receiving total marrow and involved lymphoid irradiation (TMLI) as part of the conditioning regimen before HSCT. Methods and Materials: 61 patients (7 acute myelogenous leukemia (AML), 33 acute lymphoblastic leukemia (ALL), 18 non-Hodgkin’s lymphoma (NHL), 3 mixed acute leukemia (MAL)) received conditioning radiation treatment with TMLI (8 Gy to bone marrow, 10 Gy to involved field in 2 fractions per day) in conjunction with chemotherapy before transplantation. Results: The median age of 61 patients with TMLI was 24 (4–54) years. The prescribed dose covered the entire bone and involved target volume, and the dose of organs at risk (OAR) was reduced by 28%−78% of the prescription dose. Grade 1–2 nausea and vomiting occurred in 12 patients and grade 1–2 pain in 6 patients during radiotherapy. Fatigue occurred in 16 patients. 2 patients had diarrhea, enteritis, and 1 patient had fever. None of patient had grade 3–4 non-hematologic adverse reactions. Late (30 days after HSCT) grade 2 toxicities including reversible enteritis occurred in 3 patients. 5 patients developed infectious pneumonia. The 2 years progression-free survival (PFS) was 64.1% (95% CI: 0.16–0.22) and overall survival (OS) was 74.7% (95% CI: 0.19–0.24) for the 61 patients who had received their planned HSCT. The 2-year non-relapse mortality was significantly reduced to 5% in this patient cohort. Conclusions: This study demonstrates that hypo-fractionated TMLI (8 Gy to bone marrow, 10 Gy to involved field in a single day) as a conditioning regimen for lymphoma and acute leukemia was feasible and the clinical outcomes were acceptable.

Abstract Background In the previous randomized controlled trial by our research group, we evaluated the effect of remote ischemic preconditioning (RIPC) in 130 patients (65 per arm) on acute kidney injury (AKI) within 7 days of open total aortic arch replacement. Significantly fewer RIPC-treated patients than sham-treated patients developed postoperative AKI, and, epically, RIPC significantly reduced serious AKI (stage II–III). However, the long-term effect of RIPC in patients undergoing open total aortic arch replacement is unclear. Methods This study was a post-hoc analysis. We aimed to assess the roles of RIPC in major adverse kidney events (MAKE), defined as consisting persistent renal dysfunction, renal replacement therapy and mortality, within 90 days after surgery in patients receiving open total aortic arch replacement. Results In this 90-day follow-up study, data were available for all study participants. We found that RIPC failed to improve the presence of MAKE within 90 days after surgery (RIPC: 7 of 65[10.8%]) vs sham: 15 of 65[23.1%]; P = 0.061). In those patients who developed AKI after surgery, we found that the rate of MAKE within 90 days after surgery differed between the RIPC group and the sham group (RIPC: 4 of 36[11.2%]; sham: 14 of 48[29.2%]; P = 0.046). Conclusions At 90 days after open total aortic arch replacement, we failed to find a difference between the renoprotective effects of RIPC and sham treatment. The effectiveness or ineffectiveness of RIPC should be further investigated in a large randomized sham-controlled trial. Trial registration This study was approved by the Ethics Committee of Fuwai Hospital (No. 2016–835) and our previous study was registered at clinicaltrials.gov before patient enrollment ( NCT03141385 ; principal investigator: G.W.; date of registration: March 5, 2017).

Abstract Background This cohort study aims to retrospectively investigate the incidence of severe systemic inflammatory response syndrome (sSIRS) in patients following total aortic arch replacement (TAR) under deep hypothermic circulatory arrest (DHCA) with selective cerebral perfusion and its effect on clinical outcomes. Methods All patients who underwent TAR with DHCA were consecutively enrolled from January 2013 until December 2015 at our institute. sSIRS was diagnosed between 12 and 48 h postoperatively if patients met all four criteria of the SIRS definition. Results Of the 522 patients undergoing TAR with DHCA, 31.4% developed sSIRS. Patients aged under 60 yr were characterized by a higher prevalence of sSIRS (OR = 2.93; 95% CI 2.01–4.28; P

Abstract Background Acute kidney injury (AKI) is a major postoperative morbidity of patients undergoing cardiac surgery and has a negative effect on prognosis. The kidney outcomes after pulmonary endarterectomy (PEA) have not yet been reported; However, several perioperative characteristics of PEA may induce postoperative AKI. The objective of our study was to identify the incidence and risk factors for postoperative AKI and its association with short-term outcomes. Methods This was a single-center, retrospective, observational, cohort study. Assessments of AKI diagnosis was executed based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results A total of 123 consecutive patients who underwent PEA between 2014 and 2018 were included. The incidence of postoperative AKI was 45% in the study population. Stage 3 AKI was associated with worse short-term outcomes and 90-day mortality (p

Background: The objective of this study was to compare the incidence of severe systemic inflammatory response syndrome (sSIRS) after total aortic arch replacement between patients who underwent moderate hypothermic circulatory arrest (MHCA) and those who underwent deep hypothermic circulatory arrest (DHCA).Methods: At Fuwai Hospital, 600 patients who underwent total aortic arch replacement with MHCA or DHCA from January 2013 to December 2016 were consecutively enrolled and divided into DHCA (14.1–20.0°C) and MHCA (20.1–28.0°C) groups. Preliminary statistical analysis revealed that some baseline indicators differed between the two groups; therefore, propensity score matching (PSM) was used to balance the covariates. Post-operative sSIRS as the primary outcome was compared between the groups both before and after PSM.Results: A total of 275 (45.8%) patients underwent MHCA, and 325 (54.2%) patients underwent DHCA. After PSM analysis, a total of 191 matched pairs were obtained. The overall incidence of sSIRS was 27.3%. There was no significant difference in post-operative sSIRS between the MHCA group and the DHCA group in either the overall cohort or the PSM cohort (no-PSM: P = 0.188; PSM: P = 0.416); however, post-operative sSIRS was increased by ~4% in the DHCA group compared with the MHCA group in both the no-PSM and PSM cohorts (no-PSM: 29.5 vs. 24.7%; PSM: 29.3 vs. 25.1%). Both before and after PSM, the rates of gastrointestinal hemorrhage and pulmonary infection and post-operative length of stay were significantly increased in the DHCA group compared with the MHCA group (P < 0.05), and the remaining secondary outcomes were not significantly different between the groups.Conclusions: MHCA and DHCA are associated with comparable incidences of sSIRS in patients following total aortic arch replacement for type A aortic dissection. However, the MHCA group had a shorter cardiopulmonary bypass time, a shorter post-operative length of stay and lower pulmonary infection and gastrointestinal hemorrhage rates than the DHCA group. We cautiously recommend the use of MHCA for most total arch replacements in patients with type A aortic dissection.

The low temperature solid deposition characteristics of cold spraying technology are conducive to the remanufacturing/repair of oxidation sensitive titanium alloy in the atmosphere. Ti6Al4V alloy deposits prepared by cold spray (CS) usually show porous microstructure due to insufficient plastic deformation of Ti6Al4V alloy particles. The interfacial bonding and the microstructural evolution mechanisms of Ti6Al4V particles during cold spray are still unclear. In this study, the Ti6Al4V deposits were prepared by cold spray with nitrogen as process gas at a temperature of 800 °C and a pressure of 4 MPa. The micron CT results show that the porosity is 8.25%. The deformation ultrafine grain zone and un-deformation martensitic laths zone at the bonding interface between Ti6Al4V particles were observed. The EBSD results show that the grain orientation signal was only detected at the edge of the particles deformation area and the 23% of grain sizes detected by EBSD are less than 500 nm, which indicates that the nanocrystallization induced by dynamic recrystallization occurs at the inter-particle boundaries between cold-sprayed Ti6Al4V particles. The TEM and SADPs demonstrate a gradient structure consisting of equiaxed nanograins zone, crushing dendrites transition zone and original martensitic laths zone from the interface to the core of particles.

Background: Prolonged mechanical ventilation (PMV) is common after cardiothoracic surgery, whereas the mechanical ventilation strategy after pulmonary endarterectomy (PEA) has not yet been reported. We aim to identify the incidence and risk factors for PMV and the relationship between PMV and short-term outcomes.Methods: We studied a retrospective cohort of 171 who undergoing PEA surgery from 2014 to 2020. Cox regression with restricted cubic splines was performed to identify the cutoff value for PMV. The Least absolute shrinkage and selection operator regression and logistic regressions were applied to identify risk factors for PMV. The impacts of PMV on the short-term outcomes were evaluated.Results: PMV was defined as the duration of mechanical ventilation exceeding 48 h. Independent risk factors for PMV included female sex (OR 2.911; 95% CI 1.303–6.501; P = 0.009), prolonged deep hypothermic circulatory arrest (DHCA) time (OR 1.027; 95% CI 1.002–1.053; P = 0.036), increased postoperative blood product use (OR 3.542; 95% CI 1.203–10.423; P = 0.022), elevated postoperative total bilirubin levels (OR 1.021; 95% CI 1.007–1.034; P = 0.002), increased preoperative pulmonary artery pressure (PAP) (OR 1.031; 95% CI 1.014–1.048; P < 0.001) and elongated postoperative right ventricular anteroposterior dimension (RVAD) (OR 1.119; 95% CI 1.026–1.221; P = 0.011). Patients with PMV had longer intensive care unit stays, higher incidences of postoperative complications, and higher in-hospital medical expenses.Conclusions: Female sex, prolonged DHCA time, increased postoperative blood product use, elevated postoperative total bilirubin levels, increased preoperative PAP, and elongated postoperative RVAD were independent risk factors for PMV. Identification of risk factors associated with PMV in patients undergoing PEA may facilitate timely diagnosis and re-intervention for some of these modifiable factors to decrease ventilation time and improve patient outcomes.

This paper proposes a data acquisition and analysis workflow and framework to clarify the daily residential behaviour of occupants based on the UWB indoor positioning system. The daily activities are analysed in different scales, namely grid level, convex polygon level and room level. At the first level, how long occupants stay in each 1 m*1 m grid was calculated, so that areas occupants stay longer was obtained. In the convex polygon level, the structure of the spatial network was clarified through analysis of the properties of each zone and weight of their connections. Although the network dynamically changes when the users and time differ, general patterns can be captured through analysis of large amounts of data. In the room level, which is the common analysing units, we get the movements between rooms and analysed the room-based behavioural networks of family members. Based on the findings in three levels, new variables were introduced in a regression model, and mutual visibility is found to significantly affect the household’s behaviour. By introducing the high-resolution indoor positioning system and the network analysis most used in the urban and social studies, this research provides a new prospect of data collecting and analysis of occupant indoor behaviour.

Abstract Background The cardioprotective effect of remote ischemic preconditioning (RIPC) in cardiovascular surgery is controversial. This study investigated whether RIPC combined with remote ischemic postconditioning (RIPostC) reduces myocardial injury to donor hearts in patients undergoing heart transplantation. Methods One hundred and twenty patients scheduled for orthotopic heart transplantation were enrolled and randomly assigned to an RIPC+RIPostC group (n = 60) or a control (n = 60) group. In the RIPC+RIPostC group, after anesthesia induction, four cycles of 5-min of ischemia and 5-min of reperfusion were applied to the right upper limb by a cuff inflated to 200 mmHg (RIPC) and 20 min after aortic declamping (RIPostC). Serum cardiac troponin I (cTnI) levels were determined preoperatively and at 3, 6, 12, and 24 h after aortic declamping. Postoperative clinical outcomes were recorded. The primary endpoint was a comparison of serum cTnI levels at 6 h after aortic declamping. Results Compared with the preoperative baseline, in both groups, serum cTnI levels peaked at 6 h after aortic declamping. Compared with the control group, RIPC+RIPostC significantly reduced serum cTnI levels at 6 h after aortic declamping (38.87 ± 31.81 vs 69.30 ± 34.13 ng/ml, P = 0.02). There were no significant differences in in-hospital morbidity and mortality between the two groups. Conclusion In patients undergoing orthotopic heart transplantation, RIPC combined with RIPostC reduced myocardial injury at 6 h after aortic declamping, while we found no evidence of this function provided by RIPC+RIPostC could improve clinical outcomes. Trial registration Trial Registration Number: chictr.org.cn. no. ChiCTR-INR-16010234 (prospectively registered). The initial registration date was 9/1/2017.

Metformin is still being investigated due to its potential use as a therapeutic agent for managing overweight or obesity. However, the underlying mechanisms are not fully understood. Inhibiting the adipogenesis of adipocyte precursors may be a new therapeutic opportunity for obesity treatments. It is still not fully elucidated whether adipogenesis is also involved in the weight loss mechanisms by metformin. We therefore used adipose-derived stem cells (ADSCs) from inguinal and epididymal fat pads to investigate the effects and mechanisms of metformin on adipogenesis in vitro. Our results demonstrate the similar effect of metformin inhibition on lipid accumulation, lipid droplets fusion, and growth in adipose-derived stem cells from epididymal fat pads (Epi-ADSCs) and adipose-derived stem cells from inguinal fat pads (Ing-ADSCs) cultures. We identified that cell death-inducing DFFA-like effector c (Cidec), Perilipin1, and ras-related protein 8a (Rab8a) expression increased ADSCs differentiation. In addition, we found that metformin inhibits lipid droplets fusion and growth by decreasing the expression of Cidec, Perilipin1, and Rab8a. Activation of AMPK pathway signaling in part involves metformin inhibition on Cidec, Perilipin1, and Rab8a expression. Collectively, our study reveals that metformin inhibits lipid storage, fusion, and growth of lipid droplets via reduction in Cidec and its regulatory factors in ADSCs cultures. Our study supports the development of clinical trials on metformin-based therapy for patients with overweight and obesity.

Background Moderate hypothermic circulatory arrest (MHCA) has been widely used in aortic arch surgery. However, the renal function after MHCA remains controversial. We performed a systematic review and meta‐analysis direct comparison of the postoperative renal function of MHCA versus deep hypothermic circulatory arrest (DHCA) in aortic arch surgery. Methods and Results We searched PubMed, Embase, and the Cochrane Library for postoperative renal function after aortic arch surgery with using MHCA and DHCA, published from inception to January 31, 2020. The primary outcome was renal failure. Secondary outcomes were the need for renal therapy and other major postoperative outcomes. The random‐effects model was used for all comparisons to pool the estimates. A total of 14 observational studies with 4142 patients were included. Compared with DHCA, MHCA significantly reduced the incidence of renal failure (odds ratio [OR], 0.76; 95% CI, 0.61–0.94; P=0.011; I2=0.0%) and the need of renal replacement (OR, 0.68; 95% CI, 0.48–0.97; P=0.034; I2=0.0%). Subgroup analysis showed that when the hypothermic circulatory arrest time was 30 minutes (OR, 0.76; 95% CI, 0.51–1.13; P=0.169; I2=17.3%). Conclusions MHCA compared with DHCA reduces the incidence of renal failure and the need for renal replacement. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020169348.

In the title compound (3-amino-4,4-diphenyl-BODIPY), C28H32BN3, the central six-membered ring has a flattened sofa conformation, with one of the N atoms deviating by 0.142 (4) Å from the mean plane of the other five atoms, which have an r.m.s. deviation of 0.015 Å. The dihedral angle between the two essentially planar outer five-membered rings is 8.0 (2)°. In the crystal, molecules are linked via weak N—H...π interactions, forming chains along [010]. The compound displays solvent-dependent behaviours in both NMR and fluorescence spectroscopy. In the 1H NMR spectra, the aliphatic resonance signals virtually coalesce in solvents such as chloroform, dichloromethane and dibromoethane; however, they are fully resolved in solvents such as dimethyl sulfoxide (DMSO), methanol and toluene. The excitation and fluorescence intensities in chloroform decreased significantly over time, while in DMSO the decrease is not so profound. In toluene, the excitation and fluorescent intensities are not time-dependent. This behaviour is presumably attributed to the assembly of 3-amino-4,4-diphenyl-BODIPY in solution that leads to the formation of noncovalent structures, while in polar or aromatic solvents, the formation of these assemblies is disrupted, leading to resolution of signals in the NMR spectra.

As a cytokine in interleukin-1(IL-1) family, interleukin-33(IL-33) usually exists in the cytoplasm and cell nucleus. When the cells are activated or damaged, IL-33 can be secreted into extracellular and regulate the functions of various immune cells through binding to its specific receptor suppression of tumorigenicity 2 (ST2). Except regulating the function of immune cells including T cells, B cells, dendritic cells (DCs), macrophages, mast cells, and innate lymphoid cells, IL-33 also plays an important role in metabolic diseases and has received an increasing attention. This review summarizes the regulation of IL-33 on different immune cells in lipid metabolism, which will help to understand the pathology of abnormal lipid metabolic diseases, such as atherosclerosis and type 2 diabetes.

Previous studies on wave-induced pore pressure in a porous seabed mainly focused on non-breaking regular waves, e.g., Airy linear waves or Stokes non-linear waves. In this study, breaking-wave induced pore pressure response in a sandy seabed was physically simulated with a large wave flume. The breaking-wave was generated by superimposing a series of longer waves onto the foregoing shorter waves at a specified location. Water surface elevations and the corresponding pore pressure in the process of wave breaking were measured simultaneously at three typical locations, i.e., at the rear, just at, and in front of the wave breaking location. Based on test results, characterization parameters are proposed for the wave surface elevations and the corresponding pore-pressures. Flume observations indicate that the wave height was greatly diminished during wave breaking, which further affected the pore-pressure responses. Moreover, the measured values of the characteristic time parameters for the breaking-wave induced pore-pressure are larger than those for the free surface elevation of breaking-waves. Under the action of incipient-breaking or broken waves, the measured values of the amplitude of transient pore-pressures are generally smaller than the predicted results with the analytical solution by Yamamoto et al. (1978) for non-breaking regular waves with equivalent values of characteristic wave height and wave period.

Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies.