Screening, genotyping and haematological analysis of glucose-6-phosphate dehydrogenase deficiency in the blood donors of Wuxi City, China.

BACKGROUND AND OBJECTIVES: To investigate the prevalence, genotype and haematological characteristics of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the blood donor population of Wuxi area (Jiangsu Province, China) and to assess the impact of their red blood cell (RBC) units on clinical transfusion. MATERIALS AND METHODS: We conducted genotyping and large-scale screening for G6PD enzyme activity in the blood donors of Wuxi City. In addition, we assessed the haematological parameters of G6PD-deficient and non-deficient blood donors, and investigated the adverse transfusion reactions in patients transfused with G6PD-deficient blood. RESULTS: We investigated 17,113 blood donors, among whom 44 (0.26%) were tested positive for G6PD deficiency. We identified 40 G6PD gene variants, among which c.1388G>A, c.1376G>T, c.1024C>T and c.95A>G were common. In addition, we identified two novel G6PD gene variants, c.1312G>A and c.1316G>A. The G6PD-deficient and non-deficient blood samples showed a significant difference in the RBC, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), RBC distribution width, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) values. However, the two samples showed no significant difference in the haemolysis rate at the end of the storage period. Finally, transfusion with G6PD-deficient RBC units did not lead to any adverse transfusion reactions. CONCLUSION: The positive rate of G6PD deficiency in the blood donor population of Wuxi City is 0.26%, and the genetic variants identified in this population are consistent with the common genetic variants observed in the Chinese population. Blood centres can establish a database on G6PD-deficient blood donors and mark their RBC units to avoid their use for special clinical patients.

A Comparative Study of a Nomogram and Machine Learning Models in Predicting Early Hematoma Expansion in Hypertensive Intracerebral Hemorrhage.

RATIONALE AND OBJECTIVES: Early identification for hematoma expansion can help improve patient outcomes. Presently, there are many methods to predict hematoma expansion. This study compared a variety of models to find a model suitable for clinical promotion. MATERIALS AND METHODS: Non-contrast head CT images and clinical data were collected from 203 patients diagnosed with hypertensive intracerebral hemorrhage. Radiomics features were extracted from all CT images, and the dataset was randomly divided into training and validation sets (7:3 ratio) after applying the synthetic minority oversampling method. The radiomics score (Radscore) was calculated using least absolute shrinkage and selection operator (LASSO) regression, combined with selected clinical predictors, to develop a nomogram and four machine learning (ML) models: logistic regression, random forest, support vector machine, and extreme gradient boosting (XGBoost). Discrimination, calibration and clinical usefulness of the nomogram and ML models were assessed. RESULTS: The nomogram and ML models were integrated with Radscore and clinical predictors. The nomogram demonstrated favorable discriminatory ability in the training set with an AUC of 0.80, which was confirmed in the validation set (AUC=0.76). Among the ML models, the XGBoost model achieved the highest AUC (training set=0.89 and validation set=0.85), surpassing that of the nomogram. The XGBoost model exhibited good clinical usefulness. CONCLUSION: Both the nomogram and ML models constructed by non-contrast head CT image-based Radscore integrated with clinical predictors can predict early hematoma expansion of hypertensive intracerebral hemorrhage, and the XGBoost model had the highest prediction performance and best clinical usefulness.

Performance and characterization of snail adhesive mucus as a bioflocculant against toxic Microcystis.

Toxic Microcystis blooms are widespread in aquatic bodies, posing major threats to aquatic and human life. Recently, bioflocculants have attracted considerable attention as a promising biomaterial for Microcystis management. In search of a novel organism that can produce an efficient bioflocculant for controlling harmful algae sustainably, the native gastropod Cipangopaludina chinensis was co-cultured continuously with toxic Microcystis under different initial algal cell densities. The bioflocculation effect of snail mucus on toxic Microcystis, microcystin removal, and toxin accumulation in snails was investigated. In addition, the properties of the adhesive mucus were characterized using microscopic, X-ray diffraction, infrared spectroscopy, and polysaccharide and proteome analyses. Microcystis cells were captured and flocculated by the snail mucus; removal efficiencies of up to 89.9% and 84.8% were achieved for microalgae and microcystin-leucine arginine (MC-LR), respectively, when co-cultured with C. chinensis for only one day. After nine-day exposure, less than 5.49 µg/kg DW microcystins accumulated in the snails, indicating safety for human consumption. The snail mucus contained 104.3 µg/mg protein and 72.7 µg/mg carbohydrate, which provide several functional groups beneficial for Microcystis bioflocculation. The main monosaccharide subunits of polysaccharides are galactose, galactosamine, glucosamine, fucose, glucose, and mannose. Most of them are key components of polysaccharides in many bioflocculants. Gene Ontology analysis indicated the protein enrichment in binding processes and catalytic activity, which may account for Microcystis bioflocculation via protein binding or enzymatic reactions. The findings indicate that native C. chinensis secretes adhesive mucus that can act as bioflocculant for toxic Microcystis from ambient water and can be an effective and eco-friendly tool for Microcystis suppression.

Discovery of Pyrazolo[1,5-a]pyrimidine Derivative as a Novel and Selective ALKBH5 Inhibitor for the Treatment of AML.

M6A (N6-methyladenosine) plays a significant role in regulating RNA processing, splicing, nucleation, translation, and stability. AlkB homologue 5 (ALKBH5) is an Fe(II)/2-oxoglutarate (2-OG)-dependent dioxygenase that demethylates mono- or dimethylated adenosines. ALKBH5 can be regarded as an oncogenic factor for various human cancers. However, the discovery of potent and selective ALKBH5 inhibitors remains a challenge. We identified DDO-2728 as a novel and selective inhibitor of ALKBH5 by structure-based virtual screening and optimization. DDO-2728 was not a 2-oxoglutarate analogue and could selectively inhibit the demethylase activity of ALKBH5 over FTO. DDO-2728 increased the abundance of m6A modifications in AML cells, reduced the mRNA stability of TACC3, and inhibited cell cycle progression. Furthermore, DDO-2728 significantly suppressed tumor growth in the MV4-11 xenograft mouse model and showed a favorable safety profile. Collectively, our results highlight the development of a selective probe for ALKBH5 that will pave the way for the further study of ALKBH5 targeting therapies.

An investigation on power loss of an out-to-in body wireless radio frequency link.

BACKGROUND: Implantable medical sensors for monitoring and transmitting physiological signals like blood glucose, blood oxygen, electrocardiogram, and endoscopic video present a new way for health care and disease prevention. Nevertheless, the signals transmitted by implantable sensors undergo significant attenuation as they propagate through various biological tissue layers. OBJECTIVE: This paper mainly aims to investigate the power loss of an out-to-in body wireless radio frequency link at 2.45 GHz. METHODS: Two simulation models including the single-layer human tissue model and three-layer human tissue model were established, applying the finite element method (FEM). Two experiments using physiological saline and excised porcine tissue were conducted to measure the power loss of a wireless radio frequency link at 2.45 GHz. Various communication distances and implantation depths were investigated in our study. RESULTS: The results from our measurements show that each 2 cm increase in implantation depth will result in an additional power loss of about 10 dB. The largest difference in values obtained from the measurements and the simulations is within 4 dB, which indicates that the experiments are in good agreement with the simulations. CONCLUSIONS: These results are significant for the estimate of how electromagnetic energy changes after propagating through human tissues, which can be used as a reference for the link budget of transceivers or other implantable medical devices.

Assessment of literacy and numeracy skills related to medication labels in patients on chronic in-center hemodialysis.

OBJECTIVES: Patients on hemodialysis have complicated medication regimens requiring the ability to accurately interpret medication information. Literacy and numeracy skills have been shown to differ by the types of materials provided to patients. The aims of this study were to determine prescription and over-the-counter medication label understanding and to assess the prevalence of low health literacy regarding medication labeling among in-center hemodialysis patients. DESIGN, SETTING AND PARTICIPANTS: The Medication Literacy and Numeracy in Dialysis (MedLitD) tool is an assessment of a person's ability to read and understand medication labels. A comparison with the Rapid Estimate of Adult Literacy in Medicine Short Form (REALM-SF), an established literacy tool, was conducted to determine if there were differences in the literacy results from the 2 tools that could be leveraged to target education initiatives for this specialized population. RESULTS: A total of 110 patients receiving hemodialysis from 3 dialysis facilities in the Capital Region of upstate New York were enrolled in the study. Most patients (77%) achieved a maximum REALM-SF score, indicating a high level of literacy proficiency; however, their MedLitD scores varied. Patients who were 65 years and older had lower scores on the MedLitD tool compared with younger patients. Gender, education, and the number of medications did not influence the MedLitD scores. Only 16% of all participants correctly answered the question asking for an indication of the phosphate binder (PB), although the most patients were currently taking PBs. CONCLUSION: A continuum of medication literacy levels exists among patients on hemodialysis. Appropriate evaluation of medication literacy should be done to better inform individualized education and counseling.

Assessment of literacy and numeracy skills related to non-steroidal anti-inflammatory drug labels.

BACKGROUND: Non-steroidal anti-inflammatory drugs are widely used and have a potential for over-the-counter misuse. Limited health literacy is associated with poor health outcomes. Identification of new strategies to assess literacy and numeracy could be useful in targeting effective education initiatives. OBJECTIVE: To characterize numeracy and literacy skills related to non-steroidal anti-inflammatory drug labels in primary care patients. METHODS: Patients were recruited and consented over an 8-month period after their regular primary care visit. Demographic information was collected and two instruments were administered to assess literacy and numeracy skills: (1) a medication label literacy instrument focused on non-steroidal anti-inflammatory drugs (MedLit-NSAID) and (2) a general healthy literacy-screening tool, the Newest Vital Sign. Two questions on the MedLit-NSAID instrument evaluated understanding of the Food and Drug Administration medication guide for non-steroidal anti-inflammatory drugs and the Food and Drug Administration approved over-the-counter label. RESULTS: A total of 145 patients were enrolled. Mean MedLit-NSAID and Newest Vital Sign scores were 6.8 (scale range 0-8) and 4.2 (scale range 0-6), respectively. Higher education level was associated with higher scores for both tools (p ⩽ 0.05). Total MedLit-NSAID scores on average were higher in females compared with males (6.5 vs 6, p = 0.05). Patients with decreased kidney function (n = 18) had significantly lower MedLit-NSAID scores (p ⩽ 0.05). Test-retest scores were not significantly different for MedLit-NSAID (p = 0.32). The correlation between the tools was 0.54 and internal consistency MedLit-NSAID was 0.61. CONCLUSION: A medication information focused instrument provided specific information to assess health literacy related to non-steroidal anti-inflammatory drug labels. This information could be utilized to develop patient education initiatives for medication label comprehension.

Automatic Range Adjustment of the Fluorescence Immunochromatographic Assay Based on Image Processing.

As an emerging technology, fluorescence immunochromatographic assay (FICA) has the advantages of high sensitivity, strong stability and specificity, which is widely used in the fields of medical testing, food safety and environmental monitoring. The FICA reader based on image processing meets the needs of point-of-care testing because of its simple operation, portability and fast detection speed. However, the image gray level of common image sensors limits the detection range of the FICA reader, and high-precision image sensors are expensive, which is not conducive to the popularization of the instrument. In this paper, FICA strips' image was collected using a common complementary metal oxide semiconductor (CMOS) image sensor and a range adjustment mechanism was established to automatically adjust the exposure time of the CMOS image sensor to achieve the effect of range expansion. The detection sensitivity showed a onefold increase, and the upper detection limit showed a twofold increase after the proposed method was implemented. In addition, in the experiments of linearity and accuracy, the fitting degree (R2) of the fitted curves both reached 0.999. Therefore, the automatic range adjustment method can obviously improve the detection range of the FICA reader based on image processing.

Design and feasibility study of human body communication transceiver based on FDM.

BACKGROUND: The body area networks (BAN) are built by many wearable sensors to record, monitor or control the vital signals within the human body continuously. Human body communication (HBC) is a novel physical layer method to implement the BAN with low power consumption, low radiation, and strong anti-interference. However, the most existing HBC rarely consider the situation in which multiple sensors transmit data at the same time. OBJECTIVE: The aim of this paper is to investigate the feasibility of frequency division multiplexing for human body communication multiplex data transmission. METHODS: The signal was injected into the human body, and the human channel gain was measured by the spectrum analyzer. Two frequency signals were selected with smaller gain to design the transceiver. The transmitter used OOK modulation technology to design each functional unit, and the receiver recovered the original signal with a non-coherent demodulation method. RESULTS: The experimental results show that after the dual signals were transmitted through the human body, the receiver could recover the original signal correctly. In both static and dynamic situations, even if the transmission rate was as high as 115.2 kb/s, the bit error rate was only 10-4. CONCLUSIONS: The frequency division multiplexing scheme can be selected for multi-channel data transmission in human body communication.

Electrical exposure analysis of galvanic-coupled intra-body communication based on the empirical arm models.

BACKGROUND: Intra-body communication (IBC) is one of the highlights in studies of body area networks. The existing IBC studies mainly focus on human channel characteristics of the physical layer, transceiver design for the application, and the protocol design for the networks. However, there are few safety analysis studies of the IBC electrical signals, especially for the galvanic-coupled type. Besides, the human channel model used in most of the studies is just a multi-layer homocentric cylinder model, which cannot accurately approximate the real human tissue layer. METHODS: In this paper, the empirical arm models were established based on the geometrical information of six subjects. The thickness of each tissue layer and the anisotropy of muscle were also taken into account. Considering the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines, the restrictions taken as the evaluation criteria were the electric field intensity lower than 1.35 × 104 f V/m and the specific absorption rate (SAR) lower than 4 W/kg. The physiological electrode LT-1 was adopted in experiments whose size was 4 × 4 cm and the distance between each center of adjoining electrodes was 6 cm. The electric field intensity and localized SAR were all computed by the finite element method (FEM). The electric field intensity was set as average value of all tissues, while SAR was averaged over 10 g contiguous tissue. The computed data were compared with the 2010 ICNIRP guidelines restrictions in order to address the exposure restrictions of galvanic-coupled IBC electrical signals injected into the body with different amplitudes and frequencies. RESULTS: The input alternating signal was 1 mA current or 1 V voltage with the frequency range from 10 kHz to 1 MHz. When the subject was stimulated by a 1 mA alternating current, the average electric field intensity of all subjects exceeded restrictions when the frequency was lower than 20 kHz. The maximum difference among six subjects was 1.06 V/m at 10 kHz, and the minimum difference was 0.025 V/m at 400 kHz. While the excitation signal was a 1 V alternating voltage, the electric field intensity fell within the exposure restrictions gradually as the frequency increased beyond 50 kHz. The maximum difference among the six subjects was 2.55 V/m at 20 kHz, and the minimum difference was 0.54 V/m at 1 MHz. In addition, differences between the maximum and the minimum values at each frequency also decreased gradually with the frequency increased in both situations of alternating current and voltage. When SAR was introduced as the criteria, none of the subjects exceeded the restrictions with current injected. However, subjects 2, 4, and 6 did not satisfy the restrictions with voltage applied when the signal amplitude was ≥ 3, 6, and 10 V, respectively. The SAR differences for subjects with different frequencies were 0.062-1.3 W/kg of current input, and 0.648-6.096 W/kg of voltage input. CONCLUSION: Based on the empirical arm models established in this paper, we came to conclusion that the frequency of 100-300 kHz which belong to LF (30-300 kHz) according to the ICNIRP guidelines can be considered as the frequency restrictions of the galvanic-coupled IBC signal. This provided more choices for both intensities of current and voltage signals as well. On the other hand, it also makes great convenience for the design of transceiver hardware and artificial intelligence application. With the frequency restrictions settled, the intensity restrictions that the current signal of 1-10 mA and the voltage signal of 1-2 V were accessible. Particularly, in practical application we recommended the use of the current signals for its broad application and lower impact on the human tissue. In addition, it is noteworthy that the coupling structure design of the electrode interface should attract attention.

Engineering TiO2 supported Pt sub-nanoclusters via introducing variable valence Co ion in high-temperature flame for CO oxidation.

As a typical catalytic reaction model, CO catalytic oxidation has many practical applications in gas purification. TiO2 supported Pt sub-nanoclusters have been prepared by introducing variable valence Co ions into a one step flame spray pyrolysis process. Co2+ was oxidized to Co3+ in the high-temperature flame, and the released electrons were transferred to the surface of Pt and suppressed the aggregation of Pt nanoclusters supported on TiO2. As a result, the average size of Pt nanoclusters reduced from 2.47 nm to 0.72 nm with only 1% Co2+ ion doping. Moreover, due to the presence of Co, surface oxygen species were also affected, and these changes also led to a significant increase in the catalytic activity of CO oxidation. The temperature at 100% conversion was decreased from 120 °C to 70 °C, and the TOF increased by an order of magnitude. In addition, in situ DRIFTS was also used to investigate the cause of the significant increase in activity, and it was shown that adsorbed CO species on Pt could be desorbed more easily because of the electron transfer between Pt and Co species.

Transcriptome responses to heat- and cold-stress in ladybirds (Cryptolaemus montrouzieri Mulasnt) analyzed by deep-sequencing.

BACKGROUND: Changed temperature not only threaten agricultural production, but they also affect individual biological behavior, population and community of many insects, and consequently reduce the stability of our ecosystem. Insect's ability to respond to temperature stress evolved through a complex adaptive process, thus resulting in varied temperature tolerance among different insects. Both high and low extreme temperatures are detrimental to insect development since they constitute an important abiotic stress capable of inducing abnormal biological responses. Many studies on heat or cold tolerance of ladybirds have focused on measurements of physiological and biochemical indexes such as supercooling point, higher/lower lethal temperatures, survival rate, dry body weight, water content, and developmental duration. And studies of the molecular mechanisms of ladybird responses to heat or cold stress have focused on single genes, such as those encoding heat shock proteins, but has not been analyzed by transcriptome profiling. RESULTS: In this study, we report the use of Digital Gene Expression (DGE) tag profiling to gain insight into transcriptional events associated with heat- and cold-stress in C. montrouzieri. About 6 million tags (49 bp in length) were sequenced in a heat stress group, a cold stress group and a negative control group. We obtained 687 and 573 genes that showed significantly altered expression levels following heat and cold shock treatments, respectively. Analysis of the global gene expression pattern suggested that 42 enzyme-encoding genes mapped to many Gene Ontology terms are associated with insect's response to heat- and cold-stress. CONCLUSIONS: These results provide a global assessment of genes and molecular mechanisms involved in heat and cold tolerance.

Transcriptome responses to heat- and cold-stress in ladybirds (Cryptolaemus montrouzieri Mulasnt) analyzed by deep-sequencing

BACKGROUND: Changed temperature not only threaten agricultural production, but they also affect individual biological behavior, population and community of many insects, and consequently reduce the stability of our ecosystem. Insect's ability to respond to temperature stress evolved through a complex adaptive process, thus resulting in varied temperature tolerance among different insects. Both high and low extreme temperatures are detrimental to insect development since they constitute an important abiotic stress capable of inducing abnormal biological responses. Many studies on heat or cold tolerance of ladybirds have focused on measurements of physiological and biochemical indexes such as supercooling point, higher/lower lethal temperatures, survival rate, dry body weight, water content, and developmental duration. And studies of the molecular mechanisms of ladybird responses to heat or cold stress have focused on single genes, such as those encoding heat shock proteins, but has not been analyzed by transcriptome profiling. RESULTS: In this study, we report the use of Digital Gene Expression (DGE) tag profiling to gain insight into transcriptional events associated with heat- and cold-stress in C. montrouzieri. About 6 million tags (49 bp in length) were sequenced in a heat stress group, a cold stress group and a negative control group. We obtained 687 and 573 genes that showed significantly altered expression levels following heat and cold shock treatments, respectively. Analysis of the global gene expression pattern suggested that 42 enzyme-encoding genes mapped to many Gene Ontology terms are associated with insect's response to heat- and cold-stress. CONCLUSIONS: These results provide a global assessment of genes and molecular mechanisms involved in heat and cold tolerance.

Pre-seizure state identified by diffuse optical tomography.

In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Here we demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking such brain activities with high spatiotemporal resolution. We detected early hemodynamic responses with heterogeneous patterns, along with intracranial electroencephalogram gamma power changes, several minutes preceding the electroencephalographic seizure onset, supporting the presence of a "pre-seizure" state. We also observed the decoupling between local hemodynamic and neural activities. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways.

Cortical neurovascular coupling driven by stimulation of channelrhodopsin-2.

While functional imaging is widely used in studies of the brain, how well the hemodynamic signal represents the underlying neural activity is still unclear. And there is a debate on whether hemodynamic signal is more tightly related to synaptic activity or action potentials. This study intends to address these questions by examining neurovascular coupling driven by pyramidal cells in the motor cortex of rats. Pyramidal cells in the motor cortex of rats were selectively transduced with the light sensitive cation channel channelrhodopsin-2 (ChR2). Electrophysiological recordings and optical intrinsic signal imaging were performed simultaneously and synchronously to capture the neural activity and hemodynamics induced by optical stimulation of ChR2-expressing pyramidal cells. Our results indicate that both synaptic activity (local field potential, LFP) and action potentials (multi-unit activity, MUA) are tightly related to hemodynamic signals. While LFPs in γ band are better in predicting hemodynamic signals elicited by short stimuli, MUA has better predictions to hemodynamic signals elicited by long stimuli. Our results also indicate that strong nonlinearity exists in neurovascular coupling.

Next-generation sequencing-based transcriptome analysis of Cryptolaemus montrouzieri under insecticide stress reveals resistance-relevant genes in ladybirds.

As the most efficient natural enemy of mealybugs, the ladybird Cryptolaemus montrouzieri Mulsant plays an important role in integrated pest management. We report here a profiling analysis of C. montrouzieri under insecticide stress to gain a deeper view of insecticide resistance in ladybirds. For transcriptome sequencing, more than 26 million sequencing reads were produced. These reads were assembled into 38,369 non-redundant transcripts (mean size=453 nt). 23,248 transcripts were annotated with their gene description. Using a tag-based DGE (Digital gene expression) system, over 5.7 million tags were sequenced in both the insecticide stress group and the control group, and mapped to 38,369 transcripts. We obtained 993 genes that were significantly up- or down-regulated under insecticide stress in the ladybird transcriptome. These results can contribute to in-depth research into the molecular mechanisms of resistance and enhance our current understanding of the effects of insecticides on natural enemies.

Integrated diffuse optical tomography and photoacoustic tomography: phantom validations.

We designed, fabricated and tested a novel imaging system that fuses diffuse optical tomography (DOT) and photoacoustic tomography (PAT) in a single platform. This platform takes advantages of both DOT and PAT, and can potentially provide dual-modality two dimensional functional and cellular images of the breast quantitatively. Here we describe this integrated platform along with initial tissue phantom validations.

Phase-contrast diffuse optical tomography for in vivo breast imaging: a two-step method.

We present a two-step reconstruction method that can qualitatively and quantitatively improve the reconstruction of tissue refractive index (RI) distribution by phase-contrast diffuse optical tomography (PCDOT). In this two-step method, we first recover the distribution of tissue absorption and scattering coefficients by conventional diffuse optical tomography to obtain the geometrical information of lesions, allowing the incorporation of geometrical information as a priori in the PCDOT reconstruction using a locally refined mesh. The method is validated by a series of phantom experiments and evaluated using in vivo data from 42 human subjects. The results demonstrate clear contrast of RI between the lesion and the surroundings, making the image interpretation straightforward. The sensitivity and specificity from these 42 cases are both 81% when RI is used as an imaging parameter for distinguishing between malignant and benign lesions.