Reservoir Computing Based on Oxygen-Vacancy-Mediated X-ray Optical Synaptic Device for Medical CT Bone Diagnosis.

Recognition and judgment of X-ray computed tomography (CT) images play a crucial role in medical diagnosis and disease prevention. However, the storage and calculation of the X-ray imaging system applied in the traditional CT diagnosis is separate, and the pathological judgment is based on doctors' experience, which will affect the timeliness and accuracy of decision-making. In this paper, a simple-structured reservoir computing network (RC) is proposed based on Ga2O3 X-ray optical synaptic devices to recognize medical skeletal CT images with high accuracy. Through oxygen vacancy engineering, Ga2O3 X-ray optical synaptic devices with adjustable photocurrent gain and a persistent photoconductivity effect were obtained. By using the Ga2O3 X-ray optical synaptic device as a reservoir, we constructed an RC network for medical skeletal CT diagnosis and verified its image recognition capability using the MNIST data set with an accuracy of 78.08%. In the elbow skeletal CT image recognition task, the recognition rate is as high as 100%. This work constructs a simple-structured RC network for X-ray image recognition, which is of great significance in applications in medical fields.

Pyroelectric Photoconductive Diode for Highly Sensitive and Fast DUV Detection.

Detecting high-energy photons from the deep ultraviolet (DUV) to X-rays is vital in security, medicine, industry, and science. Wide bandgap (WBG) semiconductors exhibit great potential for detecting high-energy photons. However, the implementation of highly sensitive and high-speed detectors based on WBG semiconductors has been a huge challenge due to the inevitable deep level traps and the lack of appropriate device structure engineering. Here, a sensitive and fast pyroelectric photoconductive diode (PPD), which couples the interface pyroelectric effect with the photoconductive effect based on tailored polycrystal Ga-rich GaOx (PGR-GaOx) Schottky photodiode, is first proposed. The PPD device exhibits ultrahigh detection performance for DUV and X-ray light. The responsivity for DUV light and sensitivity for X-ray are up to 104 A W-1 and 105 µC Gyair -1 cm-2, respectively. Especially, the interface pyroelectric effect induced by polar symmetry in the depletion region of the PGR-GaOx can significantly improve the response speed of the device by 105 times. Furthermore, the potential of the device is demonstrated for imaging enhancement systems with low power consumption and high sensitivity. This work fully excavates the potential of the pyroelectric effect for detectors and provides a novel design strategy to achieve sensitive and high-speed detectors.

Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a hematological malignancy of undetermined etiology, possibly linked to chromosomal structural alterations, genetic mutations, presentation and carcinogenicity of variant antigens on cell surface, and the generation of pro-inflammatory microenvironment in the bone marrow. Current drugs are unable to cure this disease, and therefore, decreasing the survival and proliferation of malignant cells to delay disease progression and extend the survival time of patients becomes the primary approach to management. In recent years, the immune system has received increasing attention for its potential role in the occurrence and development of MDS, leading to the emergence of immunoregulation as a viable treatment option. The current review provides a brief overview of pathogenesis of MDS and current treatment principles. In the meantime, the significance of immune proteins in treatment and prognosis of MDS is also discussed.

TIM3/CEACAM1 pathway involves in myeloid-derived suppressor cells induced CD8+ T cells exhaustion and bone marrow inflammatory microenvironment in myelodysplastic syndrome.

Myeloid-derived suppressor cells (MDSC) induced cellular immune deficiency and bone marrow inflammatory microenvironment play an important role in the pathogenesis and progression of myelodysplastic syndrome (MDS), but the underlying mechanism remains unclear. Here, we revealed that immune checkpoint protein TIM3 and CEACAM1 were highly demonstrated on MDSC and CD8+ T cells in MDS patients. CD8+ T cells were reduced in number and function and presented a exhaustion state. The levels of pro-inflammatory cytokines (IL-1ß, IL-18) and CEACAM1 were raised in bone marrow supernatants and MDSC culture supernatants. Blocking or neutralizing TIM3/CEACAM1 and IL-1ß/IL-18 partially reversed exhaustion of CD8+ T cells. Moreover, TIM3 correlated with NF-κB /NLRP3 inflammatory pathway. The levels of NF-κB/NLRP3/Caspase-1/IL-1ß and IL-18 were all increased in MDSC of MDS. Co-culturing MDSC from MDS patients with rhCEACAM1 enhanced NF-κB/NLRP3/Caspase-1/IL-1ß and IL-18 levels, whereas blocking TIM3 could partially reverse the above manifestations. These results indicated that TIM3/CEACAM1 pathway involved in CD8+ T cells exhaustion and might activate the NF-κB/NLRP3/Caspase-1 pathway in MDSC, increasing pro-inflammatory cytokines secretion in MDS bone marrow microenvironment. This study provided a basis for applying immune checkpoint inhibitors that could simultaneously modulate pro-inflammatory cytokine secretion and enhance anti-tumour immune function in the treatment of MDS.

Immunophenotypic changes of monocytes in myelodysplastic syndrome and clinical significance.

BACKGROUND: Myelodysplastic syndrome (MDS) is a type of heterogeneous myeloid clonal disorder usually diagnosed based on a combination of multiple laboratory examinations, including analysis of peripheral blood cells, bone marrow cell morphology and cytogenetics. However, there is a certain difficulty in cases with no distinct changes in hematology and marrow cell morphology. METHODS: We adopt flow cytometry to quantitatively analyze the immunophenotypic changes of marrow monocytes according to the surface antigens and their combinations at different differentiation stages, so as to study the changes of monocytes during differentiation in patients with bone marrow failure. In the meantime, the relationship between the immunophenotypic changes of marrow monocytes and IPSS-R score and prognosis of MDS patients was analyzed. RESULTS: Our results demonstrated disorders of maturation and differentiation of monocytes in patients with MDS and clonal cytopenias of undetermined significance as compared to those with aplastic anemia and healthy individuals. In addition, the differentiation abnormality gradually increased with the disease progression. Furthermore, CD300e expression was found to show significant associations with the clinical stage and disease progression of MDS, and the progression-free survival and AML-free survival were much longer in MDS patients highly expressing CD300e on monocytes. CONCLUSIONS: CCUS and MDS patients have disorders of differentiation and maturation of monocytes, which tends to be more critical with MDS progression or transforms to AML. Moreover, high CD300e expression has the potential to be a favorable prognostic marker for MDS. This study provides important insights to the role of monocyte immunotyping in the diagnosis, differentiation and prognosis of MDS.

Myeloid-derived suppressor cells in hematologic malignancies: two sides of the same coin.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of bone marrow cells originating from immature myeloid cells. They exert potent immunosuppressive activity and are closely associated with the development of various diseases such as malignancies, infections, and inflammation. In malignant tumors, MDSCs, one of the most dominant cellular components comprising the tumor microenvironment, play a crucial role in tumor growth, drug resistance, recurrence, and immune escape. Although the role of MDSCs in solid tumors is currently being extensively studied, little is known about their role in hematologic malignancies. In this review, we comprehensively summarized and reviewed the different roles of MDSCs in hematologic malignancies and hematopoietic stem cell transplantation, and finally discussed current targeted therapeutic strategies.Affiliation: Kindly check and confirm the processed affiliations are correct. Amend if any.correct.

High-Performance Harsh-Environment-Resistant GaOX Solar-Blind Photodetectors via Defect and Doping Engineering.

Gallium oxide (Ga2 O3 ), with an ultrawide bandgap, is currently regarded as one of the most promising materials for solar-blind photodetectors (SBPDs), which are greatly demanded in harsh environment, such as space exploration and flame prewarning. However, realization of high-performance SBPDs with high tolerance toward harsh environments based on low-cost Ga2 O3 material faces great challenges. Here, defect and doping (DD) engineering towards amorphous GaOX (a-GaOX ) has been proposed to obtain ultrasensitive SBPDs for harsh condition application. Serious oxygen deficiency and doping compensation of the engineered a-GaOX film ensure the high response currents and low dark currents, respectively. Annealing item in nitrogen of DD engineering also incurs the recrystallization of material, formation of nanopores by oxygen escape, and suppression of sub-bandgap defect states. As a result, the tailored GaOX SBPD based on DD engineering not only harvests a record-high responsivity rejection ratio (R254 nm /R365 nm ) of 1.8 × 107 , 102 times higher detectivity, and 2 × 102 times faster decay speed than the control device, but also keeps a high responsivity, high photo-to-dark current ratio, and sharp imaging capability even at high temperature (280 °C) or high bias (100 V). The proposed DD engineering provides an effective strategy towards highly harsh-environment-resistant GaOX SBPDs.

The expression and clinical significance of CD59 and FLAER in Chinese adult AML patients.

BACKGROUND: The role of CD59 and fluorescently labeled aerolysin (FLAER) in acute myeloid leukemia (AML) remains unclear and requires further investigation. To explore the relationship between CD59, FLAER, and AML, we investigated CD59 and FLAER expression in AML and analyzed their relationship with clinical characteristics of AML patients. METHODS: We employed flow cytometry (FCM) to analyze CD59 and FLAER expression in 161 AML patients at Tianjin Medical University General Hospital and evaluated its association with sex, white blood cell (WBC) count, platelet (PLT) count, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer(D-D), and lactate dehydrogenase (LDH), followed by analyzing its connection with disease progression and complete remission (CR). RESULTS: CD59 and FLAER deficiencies were identified in AML patients. Compared with CR group, non-CR group patients revealed more CD59 and FLAER deficiency. Compared with non-acute promyelocytic leukemia (M3) group, M3 group patients had more CD59 and FLAER deficiency. CD59- level in primordial cells of M3 patients was positively correlated with primordial cell ratio (r = 0.660, p = 0.003). Additionally, we discovered that the decline in CD59 and FLAER levels might be linked to higher D-D and LDH in AML patients. The difference was statistically significant (p < 0.05). CONCLUSIONS: We demonstrated that the decline in CD59 and FLAER levels was associated with leukemia cell proliferation and abnormal coagulation function in AML, suggesting that they could serve as a predictor of AML coagulation dysfunction, particularly in M3.

Safety and Efficacy of Eltrombopag and Romiplostim in Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Many studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and efficacy were not known. This meta-analysis aimed to investigate the safety and efficacy of eltrombopag and romiplostim in MDS. METHODS: A full-scale search strategy was used to search relevant published studies in PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library until January 2020 using a random-effects model and the pooled risk ratio (RR) with 95% confidence interval as the effect indicator. Statistical analyses were performed using RevMan 5.3. RESULTS: This meta-analysis included eight studies comprising 1047 patients. A lower RR of overall response rate (ORR) (RR: 0.65; 95% CI, 0.47-0.9) and grade ≥3 bleeding events (RR: 0.36; 95% CI, 0.36-0.92) were observed after romiplostim and eltrombopag treatment compared with placebo. The pooled RR for the ORR and grade ≥3 bleeding events were 0.58 (95% CI: 0.41-0.83, P = 0.003) and 0.6 (95% CI: 0.37-0.96, P = 0.03) in eltrombopag, respectively. A lower ORR in intermediate- or high-risk MDS (RR: 0.63; 95% CI: 0.45-0.88, P = 0.006) was observed. No difference in mortality, serious adverse events, platelet transfusion, hematologic improvement, and AML transformation was observed. CONCLUSIONS: Thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag were effective in reducing bleeding events, especially grade ≥3 bleeding events. However, it might reduce the ORR of MDS, especially in eltrombopag treatment group or high-risk MDS group. Due to the limited treatment of MDS and the poor response to the drug, this may be a selection method for MDS combined with fatal bleeding, although further research is needed to confirm the effectiveness of this approach.

Magnetic Resonance Imaging Research of Thoracic Inlet Parameters in the Cervical and Cervicothoracic Spine in Degenerative Cervical Spondylosis.

OBJECTIVE: The purpose of this study was to examine the thoracic inlet angle (TIA) and its related parameters in the cervical and cervical-thoracic vertebrae in patients with degenerative cervical spondylosis (DCS) and explore the association of the TIA, tilt angle of the neck, and tilt angle of the first thoracic spine with the cervical degeneration score. METHODS: Patients with DCS were included from January 2014 to December 2017. The relevant parameters were assessed on T2-weighted magnetic resonance imaging. The association of cervical parameters with the cervical degeneration score was examined by multiple linear regression model. RESULTS: A total of 204 patients (126 men) were eligible and enrolled, with a mean age of 55-56 years. Men had significantly higher thoracic inlet parameters than women (all P < 0.05). Thoracic inlet parameters were positively correlated with age (all P < 0.05). After adjustment for age and sex, the significant association between the TIA and cervical or cervical-thoracic spine degeneration scores was not observed in all vertebrae. Meanwhile, men had higher vertebral height (VH) and intervertebral disk height (IVDH) than women. Only the VHs of C7, T1, and T2 and the IVDHs of C6-7, T1-2, and T2-3 were significantly and positively associated with the TIA (all P < 0.05). CONCLUSIONS: Age was positively correlated with thoracic inlet parameters in patients with DCS. Men had significantly higher thoracic inlet parameters than women because the men had higher VHs and IVDHs. However, the TIA was not associated with the level of cervical disk degeneration. The clinical relevance of these findings has not been established.

The Alcohol Extract of Coreopsis tinctoria Nutt Ameliorates Diabetes and Diabetic Nephropathy in db/db Mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM Pathways.

The study aims to investigate the effects of the alcohol extract of Coreopsis tinctoria Nutt (AC) on diabetic nephropathy (DN) mice. A total of 30 db/db (DN) mice were divided into 3 groups, which were treated with AC (300 mg/kg/day), metformin (180 mg/kg/day), or saline by gavage for 10 weeks. Ten db/m mice treated with saline were used as normal control (NC group). Body weight (BW) and fasting blood glucose (FBG), HbA1c, 24 h urinary albumin excretion (UAE), and renal pathological fibrosis were analyzed. Expression of miR-192, miR-200b, and proteins in the PTEN/PI3K/AKT pathway was analyzed by qPCR or western blot. The DN mice had significantly higher BW, FBG, and 24 h UAE, as well as more severe pathological fibrosis when compared with NC. Treatment of AC could decrease BW, FBG, and 24 h UAE and alleviated kidney damage. Compared with the NC group, expressions of miR-192 and miR-200b were increased, whereas their target proteins (ZEB2 and PTEN) were reduced in the kidneys of DN mice, which further modulated the expression of their downstream proteins PI3K p85α, P-AKT, P-smad3, and COL4 α1; these proteins were increased in the kidneys of DN mice. In contrast, AC treatment reversed the expression changes of these proteins. These findings demonstrate that AC may protect the kidneys of DN mice by decreasing miR-192 and miR-200b, which could further regulate their target gene expression and modulate the activity of the PTEN/PI3K/AKT pathway to reduce the degree of renal fibrosis.

A New Spiropyran-Based Sensor for Colorimetric and Fluorescent Detection of Divalent Cu2+ and Hg2+ Ions and Trivalent Ce3+, Cr3+ and Al3+ Ions.

A new spiropyran derivative acts as colorimetric and fluorescent sensor for metal ions. Addition of Cu2+, Al3+, Cr3+ and Ce3+ to the sensor solution brings about marked increase in the absorption intensities while addition of other metal ions (Na+, K+, Li+, Sr2+, Hg2+, Zn2+, Co2+, Ni2+ and Ag+) fails to cause substantial change in the UV-Vis spectra. The sensor can be used for detection of Hg2+, Cu2+, Ce3+, Cr3+ and Al3+ ions by the naked eye and by fluorescence enhancement. The detection limit of Cu2+ and Hg2+ ions by the sensor is estimated to be 10 and 14 µM, respectively. Job's plot analysis on the sensor-Cu2+ complexation reveals the formation of a 2:1 stoichiometric complex between the sensor and Cu2+ ion.