Search

Abstract Apoptotic bodies (ABs) are extracellular vesicles released during apoptosis and possess diverse biological activities. Initially, ABs were regarded as garbage bags with the main function of apoptotic cell clearance. Recent research has found that ABs carry and deliver various biological agents and are taken by surrounding and distant cells, affecting cell functions and behavior. ABs-mediated intercellular communications are involved in various physiological processes including anti-inflammation and tissue regeneration as well as the pathogenesis of a variety of diseases including cancer, cardiovascular diseases, neurodegeneration, and inflammatory diseases. ABs in biological fluids can be used as a window of altered cellular and tissue states which can be applied in the diagnosis and prognosis of various diseases. The structural and constituent versatility of ABs provides flexibility for tailoring ABs according to disease diagnostic and therapeutic needs. An in-depth understanding of ABs’ constituents and biological functions is mandatory for the effective tailoring of ABs including modification of bio membrane and cargo constituents. ABs’ tailoring approaches including physical, chemical, biological, and genetic have been proposed for bench-to-bed translation in disease diagnosis, prognosis, and therapy. This review summarizes the updates on ABs tailoring approaches, discusses the existing challenges, and speculates the prospects for effective diagnostic and therapeutic applications.

Abstract Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo‐HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS‐IB‐1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow‐up was 507 days for survivors. The 2‐year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT‐CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05‐60.03, p = 0.045; HR = 3.64, 95%CI 1.40‐9.44, p = 0.008; respectively), while post‐transplantation cyclophosphamide based graft‐versus‐host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11‐0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.

Abstract Cancer immunotherapy has sparked a wave of cancer research, driven by recent successful proof-of-concept clinical trials. However, barriers are emerging during its rapid development, including broad adverse effects, a lack of reliable biomarkers, tumor relapses, and drug resistance. Integration of nanomedicine may ameliorate current cancer immunotherapy. Ultra-large surface-to-volume ratio, extremely small size, and easy modification surface of nanoparticles enable them to selectively detect cells and kill cancer cells in vivo. Exciting synergistic applications of the two approaches have emerged in treating various cancers at the intersection of cancer immunotherapy and cancer nanomedicine, indicating the potential that the combination of these two therapeutic modalities can lead to new paradigms in the treatment of cancer. This review discusses the status of current immunotherapy and explores the possible opportunities that the nanomedicine platform can make cancer immunotherapy more powerful and precise by synergizing the two approaches.

Objective To explore the risk factors for the production of anti-HLA antibodies in patients with hematological diseases before hematopoietic stemcell transplantation. Methods The results and clinical data of 1 008 patients with hematological diseases in our hospital who underwent anti-HLA antibody testing were collected by using Luminex technology platform before transplantation from 2016 to 2018 for statistical analysis. Results The total positive rate of anti-HLA antibodies in 1 008 patients was 24.08%. Multivariate analysis showed that independent risk factors associated with the production of anti-HLA antibodies included age≥30 years old(P=0.046, OR1.467, 95%CI1.007-2.136), time from disease diagnosis to antibody testing≥41 days(P=0.000, OR1.830, 95%CI1.306-2.565), initial platelet count30 U(P=0.006, OR=3.459, 95%CI1.416-8.451)are associated with the production of anti-HLA class Ⅰ and Ⅱ antibodies. Conclusion Older age, longer course of disease, lower PLT count, history of pregnancy and blood transfusion, and higher total amount of PLT transfusion are risk factors which affect the production of anti-HLA antibodies.Therefore, it is advisable to test for anti-HLA antibodies according to the situation before transplantation, which is of great value in guiding donor selection, monitoring antibody changes and improving transplant prognosis.

The terahertz range, as a type of electromagnetic wave with wavelengths between microwaves and the infrared band, has the characteristics of penetration, low energy and a stable absorption spectrum of specific substances, and is widely used in non-destructive testing, human security inspections, biological tissue diagnoses and military detection. In particular, terahertz wave 3D imaging technology can detect the internal information of the target of detection, and it has become the focus of current research. This study carried out research on 3D reconstruction and object detection algorithms based on terahertz images. In view of the problem that the MVS (Multi-ViewStereo) series of 3D reconstruction algorithms ignore the context information between the cost layers and have unsatisfactory reconstruction effects when used on complex regions, an improved MVSNet 3D reconstruction algorithm FCTMVSNet(Feature and Cost Transformer Depth Inference for Unstructured Multi-view Stereo) based on Transformer is proposed here. A structured object recognition algorithm was designed to provide theoretical support for subsequent terahertz image-based object detection algorithms.

Abstract Background Elderly patients with acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) have historically had poor prognoses. However, there has been a recent increase in the use of allogenic hematopoietic stem cell transplantation (allo-HSCT) are in this patient population. Nevertheless, the optimal choice of donor type for the patients remains an unmet need. Limited data exist on the use of allo-HSCT in elderly patients with AML/MDS from China. To better understand and optimize the selection of donor type for the elderly patients, particularly for those with refractory or relapsed disease, in comparison with the previous studies in the US and Europe. Methods Our retrospective study enrolled 259 patients aged over 55 years who underwent their first allo-HSCT between April 2015 and August 2022. These patients were divided into three groups based on donor type: haploidentical related donor group (haploidentical related donor transplantation [HID], n = 184), matched sibling donor group (matched sibling donor transplantation [MSD], n = 39), and matched unrelated donor group (matched unrelated donor transplantation [MUD], n = 36). Statistics were performed with the chi-square test, the log-rank and Fine-Gray tests. Results The median age of the cohort was 57 years (range: 55–75) and 26.25% of patients were over 60 years old. Younger patients had a higher incidence of acute graft-versus-host disease (HR = 1.942, P = 0.035), faster neutrophil recovery (HR = 1.387, P = 0.012), and better overall survival (HR = 0.567, P = 0.043) than patients aged ≥ 60 years across the entire cohort. Patients with refractory or relapsed (R/R) diseases had delayed neutrophil engraftment (P = 0.010, HR = 0.752) and platelet engraftment (P

Abstract Objective Observational studies have suggested an association between frozen shoulder (FS) and carpal tunnel syndrome (CTS). However, due to challenges in establishing a temporal sequence, the causal relationship between these two conditions remains elusive. This study, based on aggregated data from large-scale population-wide genome-wide association studies (GWAS), investigates the genetic causality between FS and CTS. Methods Initially, a series of quality control measures were employed to select single nucleotide polymorphisms (SNPs) closely associated with the exposure factors. Two-sample Mendelian randomization (MR) was utilized to examine the genetic causality between FS and CTS, employing methods including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode approaches. Subsequently, sensitivity analyses were conducted to assess the robustness of the MR analysis results. Results IVW analysis results indicate a positive causal relationship between CTS and FS (p 1), while a negative causal relationship between the two conditions was not observed. Heterogeneity tests suggest minimal heterogeneity in our IVW analysis results (p > 0.05). Multivariable MR testing also indicates no pleiotropy in our IVW analysis (p > 0.05), and stepwise exclusion tests demonstrate the reliability and stability of the MR analysis results. Gene Ontology (GO) pathway analysis reveals enrichment of genes regulated by the associated SNPs in the TGFβ-related pathways. Conclusion This study provides evidence of the genetic causal association between frozen shoulder and carpal tunnel syndrome and provides new insights into the genetics of fibrotic disorders.

Objective To investigate the clinical characteristics and diagnosis and treatment of passenger lymphocyte syndrome (PLS) in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods A total of 489 patients who underwent allo-HSCT in Suzhou Hongci Hematology Hospital were retrospectively enrolled. The clinical process, diagnosis and treatment measures and prognosis of four patients complicated with PLS after transplantation were analyzed. Results Among the 489 patients, 4 were diagnosed with PLS. The blood types of donor/recipient ABO were all secondary incompatible (The blood type of donors were O and the recipients were A or B). The overall incidence of PLS in allo-HSCT was 0.82%(4/489)and 2.2%(4/179)in transplants with donor/recipient secondary incompatible ABO-blood types. PLS occured in 6-13 days after donor stem cell infusion. Clinical manifestations were dizziness and fatigue, low back pain, jaundice, deepening urine, rapid decrease in hemoglobin on laboratory tests, elevated indirect bilirubin and lactate dehydrogenase, positive urobilinogen, positive direct anti-human globulin test (DAT), and anti-A or anti-B antibodies against recipient red blood cells were detected in plasma. After the treatment of O-type washed red blood cells, methylprednisolone, gamma globulin, rituximab and other treatments, the hemolysis was improved. All patients achieved engraftment of neutrophil and platelet. Red blood cell transfusion was halted in 3 weeks. Conclusion PLS is a rare complication of allo-HSCT, which mainly occurs in allo-HSCT patients with secondary incompatibility of ABO blood group of donor/recipient. The clinical prognosis is good after properly treatment.

BackgroundIn recent years, the addition of immune checkpoint inhibitors (ICI) to chemotherapy (CT) has become a research hotspot in the therapy of metastatic triple-negative breast cancer. Nevertheless, controversial results have been revealed among the published randomized controlled trials. Hence, a meta-analysis was performed to assess the therapeutic effect of this treatment regimen.MethodsFive English databases (PubMed, WOS, CENTRAL, Scopus, and Embase), and four Chinese databases (CBM, CNKI, VIP, and Wanfang), as well as oncological meetings, were systematically searched to identify eligible studies that assessed the addition of ICI to CT versus CT alone in metastatic triple-negative breast cancer. The pooled hazard ratios (HR) of progression-free survival (PFS) and overall survival (OS) were estimated using fixed- or random-effect model. Subgroup analyses were also performed in the intention-to-treat (ITT) and PD-L1-positive individuals.ResultsAll told there are five eligible randomized controlled trials involving 3,000 patients were enrolled in this meta-analysis. Compared with CT alone, the ICI plus CT regimen significantly increased PFS in the ITT (HR = 0.80, 95% CI: 0.73–0.88) and PD-L1-positive (HR = 0.70, 95% CI: 0.62–0.79) populations, as well as OS in the ITT (HR = 0.89, 95% CI: 0.81–0.97) and PD-L1-positive populations (HR = 0.80, 95% CI: 0.71–0.91). Moreover, the PFS of sufferers treated with the combination strategy of ICI with CT increased alongside PD-L1 enrichment. A clinical benefit in terms of objective response rate was also distinctly observed in both populations treated with ICI plus CT. In the subgroup analysis, patients in the no prior CT subgroup experienced a striking increase in PFS in both populations; however, a difference was not observed in other subgroups.ConclusionsThe combination strategy striking improves PFS and OS in both ITT and PD-L1-positive populations, and PFS is prolonged with PD-L1 enrichment. Patients who do not receive CT prior to this treatment are associated with longer PFS in both populations.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42021289817.

Objective To investigate the correlation between early immune reconstitution and clinical outcomes in patients with acute lymphoblastic leukemia (ALL) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The basic information and treatment data of 99 patients with ALL undering allo-HSCT from December 2018 to February 2022 were collected. The proportions of CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD16+CD56+ NK cells were detected before and 30, 60 and 90 days after transplantation using flow cytometry. The correlation between early cellular immune reconstitution and neutrophil engraftment, platelet engraftment, infection, and acute and chronic graft-versus-host disease (GVHD) was analyzed. Results Among 99 ALL patients, the median time of neutrophil engraftment was day +11 (range, 8-28), and the median time of platelet engraftment was day +14 (range, 10-120). The cumulative incidence of blood stream infection (BSI) was 11.10% and the cumulative incidence of CMV within 100 days of transplantation was 40.40%. The cumulative incidence of EBV within 100 days was 7.10%. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 22.30%. The cumulative incidence of chronic graft-versus-host disease (cGVHD) within 1 year of transplantation was 16.20%. 1 -year cumulative relapse rate was 13.84%. The 1 -year cumulative disease-free survival (DFS) for all patients was 80.60% and the 1-year overall survival (OS) was 90.30%. The CD4+/CD8+ ratio was positively associated with the development of aGVHD at 30 days post-transplant (OR 1.21, 95CI 1.01-1.45, P

Objective To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Methods A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). Results Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P

Terahertz waves, positioned between microwaves and infrared in the electromagnetic spectrum, are distinguished by their exceptional penetration capabilities, minimal energy requirements, and consistent absorption profiles for specific substances. Their versatility in applications such as non-destructive evaluation, human security scans, and biological diagnostics has propelled them to the forefront of scientific inquiry. However, existing terahertz equipment poses limitations in terms of compromised resolution, diffraction-induced blurring, and degradation of clarity due to texture overlaps. Consequently, numerous multi-view 3D reconstruction algorithms struggle to produce high-quality results with terahertz imagery. To address these challenges—particularly the scarcity of terahertz datasets and texture conflation—we integrated X-ray images from the DTU dataset with our collected terahertz projections. By observing inconsistent texture projections in multi-view terahertz images resulting from angle shifts, we developed DETransMVSnet—a state-of-the-art multi-view 3D reconstruction approach based on the Multi-Scale Deep Equilibrium Layer (MDEQ) paradigm. Leveraging equilibrium layers within homography-projected feature maps enables us to extract masks that differentiate different layers within a scene. The Intra-Attention and Mask-Attention Blocks further refine feature selection by preserving relevant terahertz details while suppressing disruptive background elements. As evidence of its effectiveness, DETransMVSnet achieves comparable performance to conventional algorithms on the DTU dataset but notably outperforms them when applied to terahertz datasets by successfully reconstructing images where previous methods have failed.

Background: Metformin has been shown to have potent analgesic effects; however, the underlying mechanism of synaptic plasticity mediating analgesia remained ambiguous. Methods: In this study, animal behavioral tests, whole-cell patch‑clamp recording, immunofluorescence staining, and network pharmacology techniques were applied to elucidate the mechanisms and potential targets of metformin-induced analgesia. Results: Single or consecutive injections of metformin significantly inhibited spinal nerve ligation (SNL)-induced neuropathic pain, and formalin-induced acute inflammatory pain. Network pharmacology analysis of metformin action targets in pain database-related targets revealed 25 targets, including five hub targets (nitric oxide synthase 1 (NOS1), NOS2, NOS3, epidermal growth factor receptor (EGFR), and plasminogen (PLG)). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that metformin-induced analgesia was markedly correlated with calcium signaling and synaptic transmission. Intrathecal injection of metformin significantly reversed nerve injury-induced c-Fos (neural activity biomarker) mRNA and protein expression in neuropathic rats by regulating NOS2 expression. In addition, whole-cell recordings of isolated spinal neurons demonstrated that metformin dose-dependently inhibited the enhanced frequency and amplitude of miniature excitatory synaptic currents (mEPSCs) but did not affect those of miniature inhibitory synaptic currents (mIPSCs) in neuropathic pain. Conclusions: This study further demonstrated that metformin might inhibit spinal glutamatergic transmission and abnormal nociceptive circuit transduction by monitoring synaptic transmission in pain. Results of this work provide an in-depth understanding of metformin analgesia via synaptic plasticity.

Abstract Interleukin 27 (IL-27), a heterodimeric cytokine composed of Epstein-Barr virus-induced 3 and p28, is a pleiotropic cytokine with both pro-and anti-inflammatory properties. However, the precise role of IL-27 in acute graft-versus-host disease is not yet fully understood. In this study, utilizing mice with IL-27 p28 deficiency in dendritic cells (DCs), we demonstrated that IL-27 p28 deficiency resulted in impaired Treg cell function and enhanced effector T cell responses, corresponding to aggravated aGVHD in mice. In addition, using single-cell RNA sequencing, we found that loss of IL-27 p28 impaired Treg cell generation and promoted IL-1R2+TIGIT+ pathogenic CD4+ T cells in the thymus at a steady state. Mechanistically, IL-27 p28 deficiency promoted STAT1 phosphorylation and Th1 cell responses, leading to the inhibition of Treg cell differentiation and function. Finally, patients with high levels of IL-27 p28 in serum showed a substantially decreased occurrence of grade II-IV aGVHD and more favorable overall survival than those with low levels of IL-27 p28. Thus, our results suggest a protective role of DC-derived IL-27 p28 in the pathogenesis of aGVHD through modulation of the Treg/Teff cell balance during thymic development. IL-27 p28 may be a valuable marker for predicting aGVHD development after transplantation in humans.

The bionic flapping wing aircraft realizes flight by imitating the structure and flapping mode of birds. In this paper, a three-dimensional composite motion aerodynamic analysis model of a bionic flapping wing is established. The diverting field and flapping wing grid are divided up using dynamic hybrid grid technology. The flow field of the flapping wing is analyzed by solving the Navier–Stokes (N–S) equation combined with the Boussinesq hypothesis. The lift of the flapping wing under different flutter frequencies and incoming wind speeds is studied under the asymmetric flutter condition. In order to verify the accuracy of the aerodynamic simulation results, a flapping-wing shrinking-ratio model prototype is made, and low-speed wind tunnel experiments are carried out to test the changes in the flight lift of the wing at different flutter frequencies and angles of attack. A comparative analysis of the wind tunnel experiment and the aerodynamic simulation results shows that when the flapping frequency (1–5 Hz) and incoming wind speed (1–5 m/s) increase, the lift force generated by the wing flapping increases. Due to the deviation between the experimental sample airfoil area and the simulated airfoil area, as well as the wing-driven fuselage vibration during the experiment, a sensor error is produced, resulting in a deviation of about 1 N between the experimental result curve and the simulation result curve. However, the aerodynamic characteristics obtained from the aerodynamic simulation analysis are basically consistent with the aerodynamic change law measured in the wind tunnel experiment.

Flapping-wing flight control is a multi-input and multi-output nonlinear system with uncertainties, which is affected by modeling errors, parameter variations, external disturbances, and unmodeled dynamics. Parameter uncertainty has a great impact on the stability control of flapping-wing flight, and gain adjustment is a common means to deal with parameter uncertainty, but it is complex and time-consuming. Based on the mechanism of flapping-wing flight, a nonlinear dynamic model for flapping-wing dynamic flight is established by analyzing the forces, moments, and attitude changes of the fuselage and wing in detail. Based on the constructed dynamic model, a fast robust adaptive flapping-wing flight control method is proposed. The state predictor is designed to estimate and monitor the uncertain parameters in the flapping-wing attitude control model, and the adaptive law adjusts the parameter estimation to ensure that the output error between the state predictor and the controlled object is stable in the Lyapunov sense, and finally the adaptive control law is obtained. At the same time, the Monte Carlo-support vector machine method is used to optimize the boundary of the control parameters in the flight control to obtain the control parameters that can meet the control expectations, and the obtained parameters are classified and judged according to the stable level flight conditions. Based on the adjusted parameters and the predetermined control signal, the control amount is adjusted according to the control law. When the adaptive gain is large enough, the simulation results show that the system has good transient response characteristics.

Abstract Objective To develop high-quality synthetic CT (sCT) generation method from low-dose cone-beam CT (CBCT) images by using attention-guided generative adversarial networks (AGGAN) and apply these images to dose calculations in radiotherapy. Methods The CBCT/planning CT images of 170 patients undergoing thoracic radiotherapy were used for training and testing. The CBCT images were scanned under a fast protocol with 50% less clinical projection frames compared with standard chest M20 protocol. Training with aligned paired images was performed using conditional adversarial networks (so-called pix2pix), and training with unpaired images was carried out with cycle-consistent adversarial networks (cycleGAN) and AGGAN, through which sCT images were generated. The image quality and Hounsfield unit (HU) value of the sCT images generated by the three neural networks were compared. The treatment plan was designed on CT and copied to sCT images to calculated dose distribution. Results The image quality of sCT images by all the three methods are significantly improved compared with original CBCT images. The AGGAN achieves the best image quality in the testing patients with the smallest mean absolute error (MAE, 43.5 ± 6.69), largest structural similarity (SSIM, 93.7 ± 3.88) and peak signal-to-noise ratio (PSNR, 29.5 ± 2.36). The sCT images generated by all the three methods showed superior dose calculation accuracy with higher gamma passing rates compared with original CBCT image. The AGGAN offered the highest gamma passing rates (91.4 ± 3.26) under the strictest criteria of 1 mm/1% compared with other methods. In the phantom study, the sCT images generated by AGGAN demonstrated the best image quality and the highest dose calculation accuracy. Conclusions High-quality sCT images were generated from low-dose thoracic CBCT images by using the proposed AGGAN through unpaired CBCT and CT images. The dose distribution could be calculated accurately based on sCT images in radiotherapy.

To examine the production time, type, and MFI of post-transplantation de novo HLA antibodies, and their effects on haplo-HSCT outcomes, we retrospectively included 116 patients who were negative for pre-existing HLA antibodies. In total, 322 serum samples from pre-transplantation to post-transplantation were dynamically tested by Luminex and single-antigen bead reagents. Patients were divided into: HLA antibody persistently negative group (group 1), the de novo HLA antibody transiently positive group (group 2), the de novo HLA antibody non-persistently positive group (group 3), and the de novo HLA antibody persistently positive group (group 4). Group 4 included DSA+non-DSA (NDSA) (group 4a) and NDSA (group 4b) groups. The detection rate of de novo HLA antibodies was 75.9% (88/116). The median MFI for de novo HLA antibodies was 2439 (1033-20162). The incidence of II–IV aGvHD was higher in group 2 than in group 1 (52.6% vs 17.9%, P < 0.01); in group 4a than in group 1 (87.5% vs 17.9%, P < 0.001); and in group 4a than in group 4b (87.5% vs 40.0%, P = 0.001). The DFS (37.5% vs 85.7%, P < 0.01) and OS (37.5% vs 85.7%, P < 0.01) of group 4a were lower than those of group 1. The DFS (48.0% vs 85.7%, P < 0.01) and OS (56.0% vs 85.7%, P = 0.03) of group 4b were lower than those of group 1. Multivariate analysis showed that de novo HLA antibody being transiently positive (HR: 5.30; 95% CI: 1.71–16.42, P = 0.01) and persistently positive (HR: 5.67; 95% CI: 2.00–16.08, P < 0.01) were both associated with a higher incidence of II–IV aGvHD. Persistently positive de novo HLA antibodies were a risk factor for reduced DFS (HR: 6.57; 95% CI: 2.08–20.70, P < 0.01) and OS (HR: 5.51; 95% CI: 1.73–17.53, P < 0.01). DSA and NDSA can be detected since 15 days after haplo-HSCT in patients without pre-existing HLA antibodies, and affect aGvHD, DFS, and OS. Haplo-HSCT patients must be monitored for HLA antibodies changes for appropriate preventive clinical management, and we recommend that 1-month post-transplantation is the best test time point.

Waterborne pathogens are the primary concern for the safe reuse of wastewater. Although digital PCR (dPCR) is considered promising for absolutely quantitating genes, the detection efficiency of dPCR is affected by many factors. This study tested eight virulence genes of pathogenic bacteria on a control plasmid and reclaimed water samples with reported primer–probe sets and designed ones on quantitative PCR (qPCR) and dPCR. Probe efficiency, data analysis, and PCR inhibition were found to affect the detection efficiency of dPCR. Firstly, poor probe quality, which is determined by probe quenching and activation efficiencies, was the main cause of PCR failure. Secondly, even if the PCR was successful, the probe quality and signal intensity could still affect the quantitative process. Manual analysis of dPCR data on the weak signal intensity would significantly reduce errors. And lastly, the sensitivity of PCR inhibition was lower in dPCR than qPCR, but inhibition still existed. The dPCR produced various detection efficiencies for different targets in one sample indicating inconstant inhibitory effects. Dilution was still the proper approach to overcome inhibition, but decreased the detection limit. More studies are required to ensure accurate waterborne pathogen quantitation by dPCR. HIGHLIGHTS Successful primers and probes are PCR reagent, protocol, and equipment dependent.; Probe quality is determined by quenching and activation efficiencies.; Peak separation of dPCR is critical and needed manual adjustment sometimes.; dPCR is much more inhibition-tolerant than qPCR.; PCR inhibitory effect is different for different PCR reactions.;

Rituximab is used to eliminate B cells as a chimeric monoclonal antibody directed against CD20, a B-cell antigen expressed on B cells. To explore the impact of rituximab administered before transplantation, we implemented a retrospective, monocentric study and utilized real-world data collected at our center between January 2018 and December 2020, and then followed until December 2021. Based on whether a dose of 375mg/m2 rituximab was used at least once within two weeks before transplantation, patients undergoing allo-HSCT were classified into two groups: rituximab (N=176) and non-rituximab (N=344) group. Amongst all the patients, the application of rituximab decreased EBV reactivation (P

Natural killer (NK) cells have been demonstrated as a promising cellular therapy as they exert potent anti-tumor immune responses. However, applications of NK cells to tumor immunotherapy, especially in the treatment of advanced hematopoietic and solid malignancies, are still limited due to the compromised survival and short persistence of the transferred NK cells in vivo. Here, we observed that fucosyltransferase (FUT) 7 and 8 were highly expressed on NK cells, and the expression of CLA was positively correlated with the accumulation of NK cells in clinical B cell lymphoma development. Via enzyme-mediated ex vivo cell-surface fucosylation, the cytolytic effect of NK cells against B cell lymphoma was significantly augmented. Fucosylation also promoted NK cell accumulation in B cell lymphoma-targeted tissues by enhancing their binding to E-selectin. Moreover, fucosylation of NK cells also facilitated stronger T cell anti-tumor immune responses. These findings suggest that ex vivo fucosylation contributes to enhancing the effector functions of NK cells and may serve as a novel strategy for tumor immunotherapy.

ITP is a common autoimmune bleeding disorder with elusive pathogenesis. Our study was implemented to profile the plasma metabolic alterations of patients diagnosed with ITP, aiming at exploring the potential novel biomarkers and partial mechanism of ITP. The metabolomic analysis of plasma samples was conducted using GC-MS on 98 ITP patients and 30 healthy controls (HCs). Age and gender matched samples were selected to enter the training set or test set respectively. OPLS-DA, t-test with FDR correction and ROC analyses were employed to screen out and evaluate the differential metabolites. Possible pathways were enriched based on metabolomics pathway analysis (MetPA). A total of 85 metabolites were investigated in our study and 17 differential metabolites with diagnostic potential were identified between ITP patients and HCs. MetPA showed that the metabolic disorders of ITP patients were mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and glyoxylate and dicarboxylate metabolism. Additionally, we discriminated 6 differential metabolites and 5 enriched pathways in predicting the resistance to glucocorticoids in chronic ITP patients. The distinct metabolites discovered in our study could become novel biomarkers for the auxiliary diagnosis and prognosis prediction of ITP. Besides, the dysregulated pathways might contribute to the development of ITP.

Images captured under poor illumination conditions often exhibit characteristics such as low brightness, low contrast, a narrow gray range, and color distortion, as well as considerable noise, which seriously affect the subjective visual effect on human eyes and greatly limit the performance of various machine vision systems. The role of low-light image enhancement is to improve the visual effect of such images for the benefit of subsequent processing. This paper reviews the main techniques of low-light image enhancement developed over the past decades. First, we present a new classification of these algorithms, dividing them into seven categories: gray transformation methods, histogram equalization methods, Retinex methods, frequency-domain methods, image fusion methods, defogging model methods and machine learning methods. Then, all the categories of methods, including subcategories, are introduced in accordance with their principles and characteristics. In addition, various quality evaluation methods for enhanced images are detailed, and comparisons of different algorithms are discussed. Finally, the current research progress is summarized, and future research directions are suggested.

In view of the problems existing in the defects detection for gear， a design scheme of the on-line detection system is proposed based on machine vision， and the functions such as image acquisition and display， image analysis and operation control are realized. The system controls the feeding equipment and the conveyor belt through the MCU control module， and using the photoelectric switch to trigger the high-speed camera to collect the image of the gear in real time. Then， by the industrial control machine preprocesses， the appearance quality information of the gear is obtained. Finally， the outputted signals of NG and OK are transmitted to the single chip computer to realize the sound-light alarm and sorting. Experiments show that the method has high accuracy and efficiency， and can meet the needs of actual production. It provides a new way for on-line measurement of gear.

Background/Aims: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin (Ig) superfamily that belongs to the carcinoembryonic antigen (CEA) family which plays a dual role in cancer. Previous studies showed high expression of CEACAM1 in multiple myeloma (MM). The aim of this study was to investigate the biological consequences of CEACAM1 overexpression in MM. Methods: pEGFP-N1-CEACAM1 and pcDNA3.1-CEACAM1 expression plasmids were transfected into U-266 and RPMI8266 cell lines . Effect of CEACAM1 overexpression on the proliferation of two cell lines were tested by the CCK8 assay. Cell cycle and Apoptotic changes after CEACAM1 transfection were examined with AnnexinV–FITC/PI by flow cytometry. Hochest staining assay was used to confirm the apoptotic changes. Caspase-3 activity was examined by Western blotting. The cell invasion and migration activity change after CEACAM1 transfection were performed by well chamber assays and a wound healing, respectively. MMP-2 and MMP-9 proteins expression were detected by Western blotting. Flow cytometry immunophenotyping was be evaluated on myeloma cells from bone marrow taken from 50 patients with symptomatic MM newly diagnosed. The correlations between CEACAM1 expression levels and the clinical features across all groups were investigated. Results: CEACAM1 overexpression significantly suppressed MM cell proliferation, induced cell apoptosis, and inhibited cell invasion and migration possibly through activation of caspase-3 and downregulation of MMP-2 and MMP-9. CEACAM1 expression in patients with DS stage I was more frequent (61.5%) than those with DS stage II (21.1%) or III (22.2%). Furthermore, patients with β2-microglobulin levels equal to or less than 3.5 mg/L had higher CEACAM1 expression than those with β2-microglobulin levels greater than 3.5 mg/L. Conclusion: Our findings suggest that CEACAM1 may act as a tumor suppressor in MM.

Due to the scattering of atmospheric particles, images captured under hazy conditions suffer from contrast attenuation and color distortion, which severely affect the performance of machine vision systems. Various types of methods have been developed to improve the clarity of images. However, these methods are typically challenging to apply in real-time systems. We present a fast, single-image dehazing method based on the atmospheric scattering theory and dark channel prior theory. The transmission map is approximately estimated using a fast average filter, the subsection mechanism is designed to avoid the high brightness of the sky region in the recovered image, the region projection method is adopted to obtain the atmospheric light, and image color compensation is implemented using the Weber-Fechner law. Our experimental results show that this algorithm can restore images to a clear and natural state and ensure the balance of quality and the speed of image restoration. Therefore, the algorithm can be used in real-time systems.

DRESS is one of the most severe drug reactions. The aim of this retrospective study was to summarize the clinical presentation, genetic predisposition and prognostic factors of DRESS. A total of 52 patients with DRESS, who were inpatients at a medical referral centre in Shanghai, China, from January 2011 to December 2016, were analysed retrospectively. All the patients had skin eruption, 83% had liver involvement, and ≤10% had other organ involvement. Mean cost of hospitalization was US$5,511±3,050. The 3 most common causative agents were allopurinol (18/52; 35%), salazosulphapyridine (11/52; 21%) and carbamazepine (5/52; 10%). HLA-B*5801 and HLA-B*1302 were associated with allopurinol-induced DRESS. HLA-B*1301 was related to salazosulphapyridine-induced DRESS. The mortality rate was 6% (3/52). Epstein-Barr virus DNA was found in 10 patients (19%) and indicated a poor prognosis. Human herpes virus 6 DNA was detected in 17 patients (33%) and was associated with autoimmune sequelae. Due to its high medical cost and sometimes poor prognosis, prevention of DRESS should be a high priority.

Best management practices (BMPs) are an effective way to control water pollution. However, identification of the optimal distribution and cost-effect of BMPs provides a great challenge for watershed policy makers. In this paper, a semi-distributed, low-data, and robust watershed model, the Revised Generalized Watershed Loading Function (RGWLF), is improved by adding the pollutant attenuation process in the river channel and a bank filter strips reduction function. Three types of pollution control measures—point source wastewater treatment, bank filter strips, and converting farmland to forest—are considered, and the cost of each measure is determined. Furthermore, the RGWLF watershed model is coupled with a widely recognized multi-objective optimization algorithm, the non-dominated sorting genetic algorithm II (NSGAII), the combination of which is applied in the Luanhe watershed to search for spatial BMPs for dissolved nitrogen (DisN). Fifty scenarios were finally selected from numerous possibilities and the results indicate that, at a minimum cost of 9.09 × 107 yuan, the DisN load is 3.1 × 107 kg and, at a maximum cost of 1.77 × 108 yuan, the total dissolved nitrogen load is 1.31 × 107 kg; with the no-measures scenario, the DisN load is 4.05 × 107 kg. This BMP optimization model system could assist decision-makers in determining a scientifically comprehensive plan to realize cost-effective goals for the watershed.

Patients with steroid refractory gastrointestinal (GI) tract graft- vs.-host disease (GvHD) face a poor prognosis and limited therapeutic options. To accurately assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating steroid refractory GI tract GvHD, we conducted a pilot study involving eight patients. Having received FMTs, all patients' clinical symptoms relieved, bacteria enriched, and microbiota composition reconstructed. Compared to those who did not receive FMT, these eight patients achieved a higher progression-free survival. FMT can serve as a therapeutic option for GI tract aGVHD, but its effectiveness and safety need further evaluations.Clinical Trial Registration: NCT03148743.

Natural killer (NK) cells are one group of innate lymphocytes that are important for host defense against malignancy and viruses. MicroRNAs (miRNAs) play a critical role in regulating responses of immune cells including NK cells. Accumulating evidence suggests that miR-146a is involved in the regulation of immune responses. However, the mechanism by which miR-146a regulates NK cell function is largely unknown. In the current study, we found that miR-146a intrinsically regulated NK cell function. Forced overexpression of miR-146a decreased IFN-γ production, whereas downregulation of miR-146a by anti-miR-146a significantly enhanced IFN-γ production in the human NK-92 cell line and primary human NK cells upon stimulation with IL-12 or co-stimulation with IL-12 and IL-18. Mechanistically, miR-146a regulated IFN-γ production via NF-κB, as evidenced in NK-92 cells, by downregulation of NF-κB p65 phosphorylation when miR-146a was overexpressed but upregulation of NF-κB p65 phosphorylation when anti-miR-146a was overexpressed. miR-146a directly targeted IRAK1 and TRAF6, the upstream signaling components of the NF-κB signaling pathway. This direct targeting mechanism confirmed the above gain- and loss-of-function approaches. However, the potent IFN-γ-producing subset, CD56bright NK cells, expressed higher levels of miR-146a than the lesser IFN-γ-producing subset, CD56dim NK cells. We also observed that co-stimulation of IL-12 and IL-18 significantly increased miR-146a expression in bulk NK cells and in the CD56bright subset in a time-dependent manner, correlating with augmented IFN-γ production. These data suggest that miR-146a plays a negative role in IFN-γ production by human NK cells and this miRNA may be critical in preventing NK cells from being super activated and overproducing IFN-γ.

With the development and application of next-generation sequencing (NGS) and target capture technology, the demand for an effective analysis method to accurately detect gene fusion from high-throughput data is growing. Hence, we developed a novel fusion gene analyzing method called single-end gene fusion (SEGF) by starting with single-end DNA-seq data. This approach takes raw sequencing data as input, and integrates the commonly used alignment approach basic local alignment search tool (BLAST) and short oligonucleotide analysis package (SOAP) with stringent passing filters to achieve successful fusion gene detection. To evaluate SEGF, we compared it with four other fusion gene discovery analysis methods by analyzing sequencing results of 23 standard DNA samples and DNA extracted from 286 lung cancer formalin fixed paraffin embedded (FFPE) samples. The results generated by SEGF indicated that it not only detected the fusion genes from standard samples and clinical samples, but also had the highest accuracy and sensitivity among the five compared methods. In addition, SEGF was capable of detecting complex gene fusion types from single-end NGS sequencing data compared with other methods. By using SEGF to acquire gene fusion information at DNA level, more useful information can be retrieved from the DNA panel or other DNA sequencing methods without generating RNA sequencing information to benefit clinical diagnosis or medication instruction. It was a timely and cost-effective measure with regard to research or diagnosis. Considering all the above, SEGF is a straightforward method without manipulating complicated arguments, providing a useful approach for the precise detection of gene fusion variation.