Abstract ：

Growing incidences of cardiovascular diseases have driven demand for continuous tissue oxygen metabolism monitoring. Diffuse optical spectroscopy (DOS) or near-infrared spectroscopy (NIRS) is typically employed to measure oxygenated and de-oxygenated hemoglobin, while diffuse correlation spectroscopy (DCS) provides a direct measure of tissue blood flow noninvasively. Traditionally, combined DCS and DOS/NIRS approaches are utilized for monitoring oxygen metabolism, which needs two different numerical models to calculate blood flow and oxygen saturation. In this paper, we evaluate the utility of multi-wavelength diffuse correlation spectroscopy (mwDCS) using a proposed deep learning approach, i.e., long short-term memory (LSTM) based recurrent neural network (RNN). Arterial occlusion experiments were performed in vivo to generate the data from 6 healthy individuals. Further, based on the dataset acquired by mwDCS, a LSTM-based RNN model was developed to directly assess changes of blood flow and oxygen saturation. Compared to conventional methods, the in vivo experiments in this study demonstrated a more portable system with promising results. Pearsons correlation coefficients of the proposed model reached 0.82 and 0.64 for the changes of blood flow and oxygen saturation, respectively. Our results shows that mwDCS using LSTM-based RNN model provides an alternative method for continuous tissue oxygen metabolism monitoring.

Keyword ：

Multi-wavelength diffuse correlation Oxygen metabolism monitoring Deep learning Diffuse optical spectroscopy Diffuse correlation spectroscopy spectroscopy

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Abstract ：

The process of erythroid differentiation is orchestrated at the molecular level by a complex network of transcription factors. Erythroid Kruppel-like factor (EKLF/KLF1) is a master erythroid gene regulator that directly regulates most aspects of terminal erythroid differentiation. However, the underlying regulatory mechanisms of EKLF protein stability are still largely unknown. In this study, we identified Vacuolar protein sorting 37 C (VPS37C), a core subunit of the Endosomal sorting complex required for transport-I (ESCRT-I) complex, as an essential regulator of EKLF stability. Our study showed that VPS37C interacts with EKLF and prevents K48-linked polyubiquitination of EKLF and proteasome-mediated EKLF degradation, thus enhancing EKLF protein stability and transcriptional activity. VPS37C overexpression in murine erythroleukemia (MEL) cells promotes hexamethylene bisacetamide (HMBA)-induced erythroid differentiation manifested by up-regulating erythroid-specific EKLF target genes and increasing benzidine-positive cells. In contrast, VPS37C knockdown inhibits HMBA-induced MEL cell erythroid differentiation. Particularly, the restoration of EKLF expression in VPS37C-knockdown MEL cells reverses erythroid-specific gene expression and hemoglobin production. Collectively, our study demonstrated VPS37C is a novel regulator of EKLF ubiquitination and degradation, which plays a positive role in erythroid differentiation of MEL cells by enhancing EKLF protein stability.& COPY; 2023 Elsevier Inc. All rights reserved.

Keyword ：

VPS37C EKLF Erythroid differentiation Protein stability Ubiquitination

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A novel MRI-guided near-infrared spectroscopic tomographic imaging system (NIRST) has been developed for breast cancer detection. NIRST imaging for an entire breast can be simultaneously carried out during MRI scanning in less than 4 minutes. Reconstructed phantom images showed clear contrast of a 20 mm inclusion to the background, and the total hemoglobin (HbT) and water concentration values estimated from the reconstructed images of a normal subject were in the same range as those obtained in our previous imaging studies. © 2023 SPIE.

Keyword ：

Diseases Medical imaging Optical tomography Infrared devices Magnetic resonance imaging Wearable technology Image reconstruction Phantoms

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Abstract ：

The asymmetric deformation of a laser beam reflected from the surface of a droplet on a slide was observed. The degree of deformation of the beam profile in the incident plane is related to the droplet contact angle, and the degree of deformation perpendicular to the incident plane is related to the droplet curvature. A simple, non-contact, real-time technique to measure droplet wetting parameters was established. The contact angle and radius of curvature for different liquid droplets were measured, and measurement errors were in the sub-degree and sub-millimeter orders of magnitude, respectively. The values obtained for the contact angle using the reported measurement technique compared with those obtained using a traditional measurement technique with an imaging contact angle meter showed the reported technique to be reliable. The contact angle and radius of curvature for four blood samples were measured and compared with those obtained from blood samples using a routine test. For samples with white blood cells, hemoglobin, and hematocrit exceeding the standard, their wetting parameters regularly deviated from those of normal samples. (C) 2022 Author(s).

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Coronary heart disease (CHD) is a serious complication of hypertension disease (HD). But this complication can not get timely detected, which is likely to cause serious events and result in extremely high disability rates and mortality. Therefore, early screening is important to provide early intervention to prevent the occurrence of serious events. Tongue manifestation can reflect the condition of the heart. In this paper, we applied tongue hyperspectral imaging to the early screen of the HD complicated with CHD patients. Hyperspectral data of 154 samples were collected from the department of cardiology. The wavelength range of hyperspectral data is 377. 38 similar to 1 049. 1 nm. The correlated clinical diagnosis was also recorded. Hyperspectral data of the tongue was separated into five parts according to the Chinese medicine theory, which included tongue tip, tongue left, tongue middle, tongue right and tongue root. There are maximum and minimum values at 509.6, 561.2, 540. 5 and 576. 7 nm. Moreover, this is consistent with the light absorption characteristics of hemoglobin. Then different tongue parts of the two groups were compared. The T-test results showed that there were significant differences between tongue tip and tongue middle in the wavelength region of 500 similar to 600 nm. Backpropagation artificial neural network (BPANN) was employed as an identification method for the screening whether or not complicated with CHD. The optimal results of screening model are obtained with an accuracy of 84. 78% , sensitivity of 86. 95% , and specificity of 82. 61% , respectively. Experiment results showed that there were significant differences between HD and HD-CHD hyperspectral data, and hyperspectral imaging of the tongue provides a possible way for screening HD complicated with CHD among HD patients.

Keyword ：

Coronary heart disease (CHD) Partition Chinese medicine Hypertension disease (HD) Hyperspectral imaging Tongue

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Anemia is a highly prevalent disease among older populations, with multiple adverse health outcomes, and particles exposure is a potential risk factor for anemia. However, evidence on associations of exposure to particles with small size with anemia-related blood cell parameters levels in the elderly is limited, and the underlying mechanisms are unclear. Based on a panel study in Beijing, we found that in 135 elderly participants, mass concentrations of particle with an aerodynamic diameter <= 2.5 mu m (PM2.5), black/elemental carbon (BC/EC, particle size range: 0-2.5 pm), and number concentrations of ultrafine particles (UFPs, particle size range: 5.6-93.1 nm) and accumulated mode particles (Acc, size range: 93.1-560 nm) were significantly associated with levels of red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC). The mean +/- SD for PM2.5 , UFPs, Acc, BC, OC, and EC were 69.7 +/- 61.1 mu g/m(3) , 12.5 +/- 4.3 x 10(3)/cm(3) , 1.6 +/- 1.2 x 10(3)/cm(3) , 3.0 +/- 2.0 mu g/m(3) , 8.7 +/- 6.7 mu g/m(3) , and 2.1 +/- 1.6 mu g/m(3) , respectively. Cotinine (higher than 50 ng/mL) is used as an indicator of smoking exposure. The association between MCHC difference and per interquartile range (IQR) increase in average UFPs concentration 14 d before clinical visits was -0.7% (95% CI: -1.1% to -0.3%). Significant associations of UFPs and Acc exposure with MCHC and MCH levels remain robust after adjustment for other pollutants. Furthermore, 25.2% (95% CI: 7.4% to 64.8%) and 29.8% (95% CI: 5.3% to 214.4%) of the difference in MCHC associated with average UFPs and Acc concentrations 14 d before clinical visits were mediated by the level of tumor necrosis factor alpha (TNF alpha), a biomarker of systemic inflammation. Our findings for the first time provide the evidence that shorttermUFPs and Acc exposure contributed to the damage of anemia-related blood cell in the elderly, and systemic inflammation was a potential internal mediator. (C) 2021 Elsevier B.V. All rights reserved.

Keyword ：

Anemia-related blood cell parameters Mean corpuscular hemoglobin concentration Accumulated-mode particles Elderly participants Tumor necrosis factor alpha Ultrafine particles Mediation effects

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BackgroundDrug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening drug-related complication. There are no previous reports of pemetrexed plus cisplatin as first-line chemotherapy for non-small cell lung cancer, resulting in DIIHA. Case presentationIn this report, a patient with advanced-stage lung adenocarcinoma developed severe immune hemolytic anemia 21 days after pemetrexed plus cisplatin chemotherapy. Laboratory findings showed severe hemolysis, including a rapid decrease in hemoglobin (HGB) and an elevated level of reticulocytes (Rets), indirect bilirubin (IBIL), and lactate dehydrogenase (LDH). A workup for the possibility of DIIHA was performed, including a direct antiglobulin test (DAT), a test in the presence of the soluble drug, and a drug-treated red blood cell (RBC) test. It showed a strongly positive (3+) result for anti-C3d but not for anti-immunoglobin G (IgG) in DAT. Enzyme-treated RBCs reacted weakly with the patient's serum and pemetrexed when complement was added. In addition, the patient's serum and normal sera were reactive with cisplatin-treated RBCs. However, eluates from the patient's RBCs and diluted normal sera were non-reactive with cisplatin-coated RBCs. Untreated and enzyme-treated RBCs reacted with the patient's serum in the presence of soluble cisplatin. In vitro serological tests suggested that complement-dependent pemetrexed antibodies and cisplatin-associated non-immunologic protein adsorption (NIPA) might combine to cause immune hemolytic anemia. The patient's anemia gradually recovered when pemetrexed and cisplatin were discontinued. ConclusionThis rare case demonstrated that complement-dependent pemetrexed antibodies and cisplatin-associated NIPA might occur simultaneously in a patient with DIIHA.

Keyword ：

cisplatin pemetrexed complement-dependent antibody non-immunologic protein adsorption drug-induced immune hemolytic anemia

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To enhance recombinant protein production by CHO cells, We compared the impact of overexpression of metabolic enzymes, namely pyruvate carboxylase 2 (PYC2), malate dehydrogenase Ⅱ (MDH2), alanine aminotransferase Ⅰ (ALT1), ornithine transcarbamylase (OTC), carbamoyl phosphate synthetase Ⅰ (CPSⅠ), and metabolism related proteins, namely taurine transporter (TAUT) and Vitreoscilla hemoglobin (VHb), on transient expression of anti-hLAG3 by ExpiCHO-S. Overexpression of these 7 proteins could differentially enhance antibody production. OTC, CPSI, MDH2, and PYC2 overexpression could improve antibody titer by 29.2%, 27.6%, 24.1%, and 20.3%, respectively. Specifically, OTC and MDH2 could obviously improve early-stage antibody production rate and the culture period was shortened by 4 days compared with that of the control. In addition, OTC and MDH2 had little impact on the affinity of anti-hLAG3. In most cases, overexpression of these proteins had little impact on the cell growth of ExpiCHO-S. MDH2 and ALT1 overexpression in H293T cells could also improve antibody production. Overall, overexpression of enzymes involved in cellular metabolism is an effective tool to improve antibody production in transient expression system.为提高CHO细胞重组蛋白表达量，对比研究了过表达代谢相关酶丙酮酸羧化酶 (PYC2)、苹果酸酶Ⅱ (MDH2)、丙氨酸转氨酶1 (ALT1)、鸟氨酸转氨甲酰酶 (OTC)、氨基甲酰磷酸合成酶Ⅰ (CPSⅠ) 和代谢相关蛋白牛磺酸转运蛋白 (TAUT) 及透明颤菌血红蛋白 (VHb) 对ExpiCHO-S瞬时表达anti-hLAG3的影响。结果表明，过表达上述7种蛋白均能不同程度提高抗体产量。其中，过表达OTC、CPSI、MDH2和PYC2分别能够使ExpiCHO-S抗体产量提高29.2%、27.6%、24.1%和20.3%。并且，过表达OTC和MDH2能够明显提高细胞培养初期的抗体生产速率，提前4 d达到与对照组相近的抗体产量。过表达OTC和MDH2对anti-hLAG3对抗原的亲和力基本无影响。大多数情况下，7种蛋白对细胞生长基本无影响。此外，过表达MDH2和ALT1同样能够提高H293T细胞的抗体产量。总的来说，代谢相关蛋白的过表达可以应用于瞬时表达系统，提高哺乳动物细胞的抗体产量。.

Keyword ：

anti-hLAG3 cell engineering CHO cells metabolic enzymes transient expression

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Background: Extracorporeal membrane oxygenation (ECMO) provides cardiopulmonary support for critically ill patients. Portable ECMO devices can be applied in both in-hospital and out-of-hospital emergency conditions. We evaluated the safety and biocompatibility of a novel centrifugal pump and ECMO device of the OASSIST ECMO System (Jiangsu STMed Technologies Co., Suzhou, China) in a 168-h ovine ECMO model. Methods: The portable OASSIST ECMO system consists of the control console, the pump drive, and the disposable centrifugal pump. Ten healthy sheep were used to evaluate the OASSIST ECMO system. Five were supported on veno-venous ECMO and five on veno-arterial ECMO, each for 168 h. The systemic anticoagulation was achieved by continuous heparin infusion to maintain the activated clotting time (ACT) between 220 and 250 s. The rotary speed was set at 3,200-3,500 rpm. The ECMO configurations and ACT were recorded every 6 hours (h). The free hemoglobin (fHb), complete blood count, and coagulation action test were monitored, at the 6th h and every 24 h after the initiation of the ECMO. The dissection of the pump head and oxygenator were conducted to explore thrombosis. Results: Ten sheep successfully completed the study duration without device-related accidents. The pumps ran stably, and the ECMO flow ranged from 1.6 +/- 0.1 to 2.0 +/- 0.11 L/min in the V-V group, and from 1.8 +/- 0.1 to 2.4 +/- 0.14 L/min in the V-A group. The anticoagulation was well-performed. The ACT was maintained at 239.78 +/- 36.31 s, no major bleeding or thrombosis was observed during the ECMO run or in the autopsy. 3/5 in the V-A group and 4/5 in the V-V group developed small thrombus in the bearing pedestal. No obvious thrombus formed in the oxygenator was observed. The hemolytic blood damage was not significant. The average fHb was 0.17 +/- 0.12 g/L. Considering hemodilution, the hemoglobin, white blood cell, and platelets didn't reduce during the ECMO runs. Conclusions: The OASSIST ECMO system shows satisfactory safety and biocompatibility for the 168-h preclinical evaluation in the ovine model. The OASSIST ECMO system is promising to be applied in clinical conditions in the future.

Keyword ：

extracorporeal membrane oxygenation critical care ovine model preclinical evaluation centrifugal pump

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Exercise training can mitigate symptoms of claudication (walking-induced muscle pain) in patients with peripheral artery disease (PAD). One adaptive response enabling this improvement is enhanced muscle oxygen metabolism. To explore this issue, we used arterial-occlusion diffuse optical spectroscopy (AO-DOS) to measure the effects of exercise training on the metabolic rate of oxygen (MRO2) in resting calf muscle. Additionally, venous-occlusion DOS (VO-DOS) and frequency-domain DOS (FD-DOS) were used to measure muscle blood flow (F) and tissue oxygen saturation (StO(2)), and resting calf muscle oxygen extraction fraction (OEF) was calculated from MRO2, F, and blood hemoglobin. Lastly, the venous/arterial ratio (gamma) of blood monitored by FD-DOS was calculated from OEF and StO(2). PAD patients who experience claudication (n = 28) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 months of supervised exercise training. Optical measurements were obtained at baseline and at 3 months in both groups. Resting MRO2, OEF, and F, respectively, increased by 30% (12%, 44%) (p < 0.001), 17% (6%, 45%) (p = 0.003), and 7% (0%, 16%) (p = 0.11), after exercise training (median (interquartile range)). The pre-exercise gamma was 0.76 (0.61, 0.89); it decreased by 12% (35%, 6%) after exercise training (p = 0.011). Improvement in exercise performance was associated with a correlative increase in resting OEF (R = 0.45, p = 0.02).

Keyword ：

exercise training diffuse optical spectroscopy peripheral artery disease claudication

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