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BackgroundFatigue driving is an important cause of road traffic accidents in modern society, and the fatigue condition of heavy-duty commercial truck drivers has attracted widespread attention. Research on the fatigue status and influencing factors of heavy-duty commercial truck drivers in China is relatively rare at present. ObjectiveTo analyze the main characteristics of fatigue among heavy-duty commercial truck drivers and the impacts of factors such as working hours, insomnia, and occupational burnout on their fatigue status. MethodsUsing cluster sampling method, a cross-sectional study was conducted from July to August 2023, enrolling heavy-duty commercial truck drivers in long-distance freight logistics markets (stations) located in three administrative regions of W City, Xinjiang Uygur Autonomous Region. A self-designed questionnaire was used to collect demographic and occupational characteristics of heavy-duty commercial truck drivers, and the Chinese versions of Fatigue Scale-14 (FS-14), Athens Insomnia Scale (AIS), and Maslach Burnout Inventory General Survey (MBI-GS) were used to evaluate their fatigue, insomnia, and occupational burnout status, respectively. Mann-Whitney U test and Kruskal-Walls H test were used to compare intergroup differences, and Spearman correlation coefficient was used to analyze the correlation between variables. Hierarchical regression models were used to study the impacts of selected variables on fatigue status. ResultsThis study obtained 311 valid questionnaires, with a valid recovery rate of 88.86% (311/350). The physical fatigue, mental fatigue, and total fatigue scores of the survey subjects in M (P25, P75) were 3.00 (2.00, 4.00), 2.00 (1.00, 3.00), and 5.00 (4.00, 6.00), respectively. The comparison results showed that, except for smoking, there were statistically significant differences in total fatigue scores between different groups of age, marital status, number of children, educational level, service length of freight transportation, average daily working time, and average monthly income (P

Summary: Background: Vascular dysfunction is closely associated with the progression of Alzheimer's disease (AD). A critical research gap exists that no studies have explored the in vivo temporal changes of cerebrovascular alterations with AD progression in mouse models, encompassing both structure and flow dynamics at micron-scale resolution across the early, middle, and late stages of the disease. Methods: In this study, ultrasound localisation microscopy (ULM) was applied to image the cerebrovascular alterations of the transgenic female 5×FAD mouse model across different stages of disease progression: early (4 months), moderate (7 months), and late (12 months). Age-matched non-transgenic (non-Tg) littermates were used as controls. Immunohistology examinations were performed to evaluate the influence of disease progression on the β-amyloid (Aβ) load and microvascular alterations, including morphological changes and the blood–brain barrier (BBB) leakage. Findings: Our findings revealed a significant decline in both vascular density and flow velocity in the retrosplenial cortex of 5×FAD mice at an early stage, which subsequently became more pronounced in the visual cortex and hippocampus as the disease progressed. Additionally, we observed a reduction in vascular length preceding diminished flow velocities in cortical penetrating arterioles during the early stages. The quantification of vascular metrics derived from ULM imaging showed significant correlations with those obtained from vascular histological images. Immunofluorescence staining identified early vascular abnormalities in the retrosplenial cortex. As the disease advanced, there was an exacerbation of Aβ accumulation and BBB disruption in a regionally variable manner. The vascular changes observed through ULM imaging exhibited a negative correlation with amyloid load and were associated with the compromise of the BBB integrity. Interpretation: Through high-resolution, in vivo imaging of cerebrovasculature, this study reveals significant spatiotemporal dysfunction in cerebrovascular dynamics accompanying disease progression in a mouse model of AD, enhancing our understanding of its pathophysiology. Funding: This study is supported by grants from National Key Research and Development Program of China (2020YFA0908800), National Natural Science Foundation of China (12074269, 82272014, 82327804, 62071310), Shenzhen Basic Science Research (20220808185138001, JCYJ20220818095612027, JCYJ20210324093006017), STI 2030-Major Projects (2021ZD0200500) and Guangdong Natural Science Foundation (2024A1515012591, 2024A1515011342).

Abstract Visualization of photothermal therapy mediated by photothermal transduction agents (PTAs) is important to promote individual treatment of patients with low side effects. Photoacoustic detection has emerged as a promising noninvasive method for the visualization of PTAs distribution but still has limitations in temperature measurement, including poor measurement accuracy and low tissue penetration depth. In this study, we developed biocompatible semiconducting polymer dots (SPD) for in situ coupling of photothermal and photoacoustic detection in the near-infrared II window. SPD has dual photostability under pulsed laser and continuous-wave laser irradiation with a photothermal conversion efficiency of 42.77%. Meanwhile, a strong correlation between the photoacoustic signal and the actual temperature of SPD can be observed. The standard deviation of SPD-mediated photoacoustic thermometry can reach 0.13 °C when the penetration depth of gelatin phantom is 9.49 mm. Preliminary experimental results in vivo show that SPD-mediated photoacoustic signal has a high signal-to-noise ratio, as well as good performance in temperature response and tumor enrichment. Such a study not only offers a new nanomaterial for the visualization of photothermal therapy but will also promote the theranostic platform for clinical applications.

Background: Although amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease and unfortunately incurable yet, incremental attention has been drawn to targeting the health of corticospinal motor neurons. Focused ultrasound combined with systemically circulating microbubbles (FUS/MB) is an emerging modality capable of site-specific molecular delivery temporarily and noninvasively within a range of appropriate parameters. Objective: To investigate the effect of FUS/MB–enhanced delivery of therapeutics to the motor cortex on the disease progression by using a transgenic mouse model of ALS. Methods: Multiple FUS/MB–enhanced deliveries of Edaravone (Eda) to the motor cortex were performed on the SOD1G93A mouse model of ALS. The motor function of the animals was evaluated by gait analysis, grip strength and wire hanging tests. Corticospinal and spinal motor neuronal health, misfolded SOD1 protein and neuroinflammation after treatments were evaluated by histological examination. Results: Ultrasound–enhanced delivery of Eda in the targeted motor cortex was achieved by a two-fold increase without gross tissue damage. Compared with the ALS mice administered Eda treatments only, the animals given additionally FUS/MB–enhanced brain delivery of Eda (FUS/MB + Eda) exhibited further improvements in neuromuscular functions characterized by gait patterns, muscular strength, and motor coordination along with rescued muscle atrophy. FUS/MB + Eda treatments conferred remarkable neuroprotection to both upper and lower motor neurons revealed by normalized neuronal morphology with increasing cell body size and profoundly alleviated neuroinflammation and misfolded SOD1 protein in the brains and lumbar spinal cords. Conclusion: We report a pilot study that non-invasive ultrasound–enhanced brain delivery of Eda provides additive amelioration on disease progression of ALS and suggest that broadening the target from spinal to cortical network functions using the FUS/MB–enhanced delivery can be a rational therapeutic strategy of this debilitating disorder.

Abstract Pancreatic diseases, a serious threat to human health, have garnered considerable research interest, as they are associated with a high mortality rate. However, owing to the uncertain etiology and complex pathophysiology, the treatment of pancreatic diseases is a challenge for clinicians and researchers. Exosomes, carriers of intercellular communication signals, play an important role in the diagnosis and treatment of pancreatic diseases. Exosomes are involved in multiple stages of pancreatic disease development, including apoptosis, immune regulation, angiogenesis, cell migration, and cell proliferation. Thus, extensive alterations in the quantity and variety of exosomes may be indicative of abnormal biological behaviors of pancreatic cells. This phenomenon could be exploited for the development of exosomes as a new biomarker or target of new treatment strategies. Several studies have demonstrated the diagnostic and therapeutic effects of exosomes in cancer and inflammatory pancreatic diseases. Herein, we introduce the roles of exosomes in the diagnosis and treatment of pancreatic diseases and discuss directions for future research and perspectives of their applications.

Abstract Background We have improved and named a new reverse rolling-mat type lymph node dissection, which effectively solves the dilemma faced by the traditional lymph node dissection in hand-assisted laparoscopic D2 radical gastrectomy through the optimization of the surgical procedure. However, the relevant clinical data are still scarce. The study aims to compare the clinical effects of two surgical procedure and explore the safety and feasibility of “reverse procedure”. Study design The clinicopathological data of 195 patients who underwent hand-assisted D2 radical total gastrectomy (HALTG) in our hospital from January 2011 to September 2017 were collected. A retrospective case–control study was used to compare the clinical outcomes of the two patterns of lymph node dissection. Among them, 89 patients underwent “cabbage type” lymph node dissection and 106 patients underwent the “reverse procedure” lymph node dissection. Results There were no significant differences between the two groups of patients in terms of gender, age, tumor location, incision length, postoperative hospitalization duration, pathological classification, recent complications, long-term recurrence and metastasis. The operation time of “cabbage type” group was shorter than that of “reverse procedure” group (178.35 ± 31.52 min vs 191.25 ± 32.77 min; P = 0.006). While, in the “reverse procedure” group, intraoperative blood loss was less (249.4 ± 143.12 vs 213.58 ± 101.43; P = 0.049), and there were more numbers of lymph nodes dissected (18.04 ± 7.00 vs 32.25 ± 14.23; P

Recently, emerging evidence has demonstrated that cavitation actually creates important bidirectional channels on biological barriers for both intratumoral drug delivery and extratumoral biomarker release. To promote the barrier-breaking effects of cavitation for both therapy and diagnosis, we first reviewed recent technical advances of ultrasound and its contrast agents (microbubbles, nanodroplets, and gas-stabilizing nanoparticles) and then reported the newly-revealed cavitation physical details. In particular, we summarized five types of cellular responses of cavitation in breaking the plasma membrane (membrane retraction, sonoporation, endocytosis/exocytosis, blebbing and apoptosis) and compared the vascular cavitation effects of three different types of ultrasound contrast agents in breaking the blood-tumor barrier and tumor microenvironment. Moreover, we highlighted the current achievements of the barrier-breaking effects of cavitation in mediating drug delivery and biomarker release. We emphasized that the precise induction of a specific cavitation effect for barrier-breaking was still challenged by the complex combination of multiple acoustic and non-acoustic cavitation parameters. Therefore, we provided the cutting-edge in-situ cavitation imaging and feedback control methods and suggested the development of an international cavitation quantification standard for the clinical guidance of cavitation-mediated barrier-breaking effects.

Rapid, sensitive and visual detection of plant viruses is conducive to effective prevention and control of plant viral diseases. Therefore, combined with reverse transcription and recombinase-aided amplification, we developed a CRISPR/Cas12a-based visual nucleic acid detection system targeting sorghum mosaic virus and rice stripe mosaic virus, which cause harm to crop production in field. When the RT-RAA products were recognized by crRNA and formed a complex with LbCas12a, the ssDNA labeled with a quenched green fluorescent molecule will be cleaved by LbCas12a, and then a significant green fluorescence signal will appear. The entire detection process can be completed within 30 min without using any sophisticated equipment and instruments. The detection system could detect samples at a dilution of 107, about 104-fold improvement over RT-PCR, so the system was successfully to detect rice stripe mosaic virus in a single leafhopper, which is the transmission vector of the virus. Finally, the CRISPR/Cas12a-based detection system was utilized to on-site detect the two viruses in the field, and the results were fully consistent with that we obtained by RT-PCR in laboratory, demonstrating that it has the application prospect of detecting important crop viruses in the field.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive deposition of fatty acids in the liver. Further deterioration leads to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, creating a heavy burden on human health and the social economy. Currently, there are no effective and specific drugs for the treatment of NAFLD. Therefore, it is important to further investigate the pathogenesis of NAFLD and explore effective therapeutic targets for the prevention and treatment of the disease. Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a STEAP family protein, is a metalloreductase. Studies have shown that it can participate in the regulation of liver ischemia-reperfusion injury, hepatocellular carcinoma, myocardial hypertrophy, and other diseases. In this study, we found that the expression of STEAP3 is upregulated in NAFLD. Deletion of STEAP3 inhibits the development of NAFLD in vivo and in vitro, whereas its overexpression promotes palmitic acid/oleic acid stimulation-induced lipid deposition in hepatocytes. Mechanistically, it interacts with transforming growth factor beta-activated kinase 1 (TAK1) to regulate the progression of NAFLD by promoting TAK1 phosphorylation and activating the TAK1-c-Jun N-terminal kinase/p38 signaling pathway. Taken together, our results provide further insight into the involvement of STEAP3 in liver pathology.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common liver diseases. Ultrasound elastography has been used for the diagnosis of NAFLD. However, clinical research on steatosis by elastography technology has mainly focused on steatosis with fibrosis or non-alcoholic steatohepatitis (NASH), while steatosis without fibrosis has been poorly studied. Moreover, the relationship between liver viscoelasticity and steatosis grade is not clear. In this study, we evaluated the degree of liver steatosis in a simple steatosis rat model using shear wave elastography (SWE). Results The viscoelasticity values of 69 rats with hepatic steatosis were measured quantitatively by SWE in vivo and validated by a dynamic mechanical analysis (DMA) test. Pathological sections were used to determine the steatosis grade for each rat. The results showed that the elasticity values µ obtained by the two methods followed the same trend, and µ is significantly correlated with liver steatosis. The Pearson’s correlation coefficients indicate that $$\mu$$ μ obtained by SWE is positively linear correlated with DMA (r = 0.628, p = 7.85 × 10–9). However, the viscosity values $$\eta$$ η obtained by SWE were relatively independent of those obtained by DMA with a correlation coefficient of − 0.01. The combined Voigt elasticity measurements have high validity in the prediction of steatosis (S0 vs. S1–S4), with an AUROC of 0.755 (95% CI 0.6175–0.8925, p

Ultrasound computed tomography (USCT) can visualize a target with multiple imaging contrasts, which were demonstrated individually previously. Here, to improve the imaging quality, the dynamic speed of sound (SoS) map derived from the transmission USCT will be adapted for the correction of the acoustic speed variation in the reflection USCT. The variable SoS map was firstly restored via the optimized simultaneous algebraic reconstruction technique with the time of flights selected from the transmitted ultrasonic signals. Then, the multi-stencils fast marching method was used to calculate the delay time from each element to the grids in the imaging field of view. Finally, the delay time in conventional constant-speed-assumed delay and sum (DAS) beamforming would be replaced by the practical computed delay time to achieve higher delay accuracy in the reflection USCT. The results from the numerical, phantom, and in vivo experiments show that our approach enables multi-modality imaging, accurate target localization, and precise boundary detection with the full-view fast imaging performance. The proposed method and its implementation are of great value for accurate, fast, and multi-modality USCT imaging, particularly suitable for highly acoustic heterogeneous medium.

Fetal heart rate (FHR) is an essential indicator of fetal well-being. The ultrasonic Doppler FHR detector is widely used to monitor the fetus’s health due to its advantages of non-invasion, high sensitivity, and good directivity. However, the existing commercial Doppler FHR detector primarily uses an analog multiplier for demodulation, which has limited functions and insufficient sensitivity. The analog demodulation is performed only on a single-sideband signal(in-phase or quadrature) (IQ), which is impossible to derive the fetal heart movement’s vector velocity. Moreover, repetitive recognition of the mitral valve’s positive and negative motion easily causes the measured FHR twice the actual one (FHR doubling). Although the traditional digital demodulation FHR detector can obtain in-phase and quadrature demodulation signals, it needs a high-level field-programmable gate array chip and therefore cannot meet low-power consumption requirements in battery-powered situations. Herein we proposed a novel digital demodulation FHR algorithm using time-domain windowing. Then, we applied the algorithm into a low-power complex programmable logic device to achieve low-cost acquisition of vector velocity and suppress FHR doubling and finally designed a hand-held, noninvasive digital Doppler FHR detection system for continuous perinatal detection. In this work, the comparison curve between the TREND curve generated by the simulator and the measured curve of our FHR detector was obtained. The comparative experiment between the commercial FM-3A FHR detector and our proposed FHR detector was performed, and the relative error and standard error of the obtained FHR data were used to evaluate the two FHR detectors’ detection accuracy. The results showed that our FHR detector showed excellent detection accuracy at an accuracy rate of 98%, which was much higher than the average accuracy of the FM-3A FHR detector and indicated our proposed digital FHR detector showed excellent detection performance. It means that the proposed digital windowed FHR demodulation algorithm is practical, the multi-FHR monitoring system is feasible, and our proposed FHR detector has high detection accuracy, effectively suppresses FHR doubling, and meets the requirements of Chinese national standards. It provides an alternative scheme towards the low-cost hand-held digital demodulation FHR detection application.

Abstract Background Salmonella is one of the main causative agents of diarrhea which results in substantial disease burden. To determine the prevalence, serotype distribution, and antimicrobial resistance profiles of clinical Salmonella isolates in Shenzhen, a 6-year surveillance study was conducted. Results A total of 297 (5.7%) Salmonella strains were isolated from stool samples from 5239 patients. Among the 42 serotypes identified, serotype Typhimurium was the most common one which represented 39.7% of the isolates (118), followed by serotype Enteritidis (71, 23.9%), London (12, 4.0%), 4, 5, 12: i: - (11, 3.7%), and Senftenberg (8, 2.7%). A high frequency of resistance was found in ampicillin (70.6%), piperacillin (64.5%), tetracycline (63.5%), and streptomycin (54.3%). Resistance to ampicillin and tetracycline was observed in 95.3% of S. Typhimurium isolates; and nalidixic acid in 93.1% of S. Enteritidis isolates. Resistance to 5 or more antimicrobial agents was found in 78.8% of S. Typhimurium and 69.0% of S. Enteritidis isolates. A decreased susceptibility to ciprofloxacin and levofloxacin was associated with amino acid alteration in gyrA gene. Point mutations without amino acid changes were seen in gyrB, parC, and parE genes. Conclusions A broad range of serotypes are responsible for Salmonellosis in Shenzhen, with Enteritidis and Typhimurium being the most common serotypes. The high level of antibiotic resistance is of public health significance and ongoing monitoring combined with rational use of antibiotics are recommended. Point mutations in gyrA gene might play an important role in the resistance to fluoroquinolones.

Abstract Background Colorectal cancer is the third leading cause of cancer-related deaths worldwide. Sonodynamic therapy (SDT) is an emerging cancer therapy, and in contrast to photodynamic therapy, could non-invasively reach deep-seated tissues and locally activates a sonosensitizer preferentially accumulated in the tumor area to produce cytotoxicity effects. In comparison with traditional treatments, SDT may serve as an alternative strategy for human colon cancer treatment. Here, we investigated the sonodynamic effect using sinoporphyrin sodium (DVDMS) as a novel sonosensitizer on human colon cancer cells in vitro. Results The absorption spectra of DVDMS revealed maximum absorption at 363 nm wavelength and emission peak at 635 nm. Confocal microscopy images revealed the DVDMS was primarily localized in the cytoplasm, while no evident signal was detected within the nuclei. Flow cytometry analysis showed rapid intracellular uptake of DVDMS by two types of human colon cancer cells (HCT116 and RKO). Cell viability of HCT116 was tolerant with the concentration of DVDMS up to 20 µg/mL, while the case of RKO was 5 µg/mL. In comparison with the control group, the SDT-treated groups of these two types of human colon cancer cells showed significant increase in cellular apoptosis and necrosis ratio. Increased intracellular reactive oxygen species (ROS) production was detected, indicating the involvement of ROS in mediating SDT effects. Conclusion DVDMS results an effective sonosensitizer for the ultrasound-mediated cancer cell killing, and its anticancer effect seems to rely on its ability to produce ROS under ultrasound exposure.

Magneto-Acousto-Electrical Tomography (MAET) is a novel multi-physics imaging method, which promises to offer a unique biophysical property of tissue electrical impedance with the additional benefit of excellent spatial resolution of the ultrasonic imaging. It opens the potential for early diagnosis of cancer by revealing changes of dielectric characteristics. However, direct MAET is unable to image the irregularly-shaped lesions fully due to the dependence on the angle between conductivity boundary and ultrasound beam direction. In this paper, a numerical simulation of multi-angle MAET is presented for an improved image reconstruction for MAET in order to discern irregularly-shaped tumors in different positions. The results show that the conductivity boundary interfaces are invisible in single angle B-mode reconstructed image, wherever the ultrasound beam and conductivity boundary are nearly parallel. When the multi-angle scanning was adopted, the image reconstructed with image rotation method reproduced the original object pattern. Furthermore, the relationship between reconstruction error and the number of angles was also discussed. It is found that 12 angles would be necessary to achieve nearly the optimal reconstruction. Finally, reconstructed images in L2 norm of the error with the measurement noise are presented.

As the conductivities of healthy tissue and cancerous tissue are different, methods for detecting conductivity variations of biological tissue are potential medical imaging modalities for early diagnosis of cancer in the future. Magneto-acousto-electrical tomography (MAET) is a noninvasive and hybrid conductivity imaging technology that integrates the advantage of high contrast. It has been demonstrated to have an excellent capability to distinguish conductivity variations along the direction of acoustic propagation and extremely promising as an alternative medical imaging technology for early detection of cancer. However, the existing MAET has a low resolution, and the factors affecting the imaging resolution of MAET are rarely studied systematically. Therefore, we firstly designed an MAET detection system and performed several verification experiments. A B-scan algorithm was then proposed for enhancing the system resolution. Subsequently, two uniform phantoms with different intermediate gaps in the middle and a B-mode imaging experiment on pork tissue were used for testing the performance of detection resolution. Finally, comparative analyses were performed to verify whether the frequency, the cycle number of the excitation signal, and the B-scan algorithm can influence the detection resolution. We obtained the following results: 1) The longitudinal resolution of the conductivity B-scan image increases as the number of cycle excitation decreases. 2) Vertical resolution using a 2.5 MHz probe excitation is significantly better than using a 500 kHz probe excitation. 3) The B-scan algorithm can improve conductivity resolution, and it reveals that our proposed detection system's longitudinal resolution can reach 1mm. 4) we obtained the conductivity profile of pork tissue. The results showed that our detection platform could accurately distinguish the target sample's interfaces of conductivity variations, increasing the excitation frequency, reducing the cycle number, and adopting the B-mode imaging algorithm could improve its conductivity detection resolution, which laid the foundation for the design of a high-resolution MAET detection system.

Abstract Background Rice stripe mosaic virus (RSMV) is a tentative new Cytorhabdovirus species in family Rhabdoviridae transmitted by the leafhopper Recilia dorsalis. Although the virus was first detected in southern China in 2015, few studies have investigated rice symptoms and yield losses caused by RSMV infection. Methods In this study, we observed and systematically compared symptoms of three virally infected, representative varieties of indica, hybrid and japonica rice and determined the yield parameters of the artificially inoculated plants. Results The three RSMV-infected cultivated rice varieties exhibited slight dwarfing, striped mosaicism, stiff, crinkled or even twisted leaves, an increased number of tillers, delayed heading, cluster-shaped shortening of panicles and mostly unfilled grains. Slight differences in symptom occurrence time were observed under different environmental conditions. For example, mosaic symptoms appeared earlier and crinkling symptoms appeared later, with both symptoms later receding in some infected plants. Yield losses due to RSMV also differed among varieties. The most serious yield reduction was experienced by indica rice (cv. Meixiangzhan), followed by hybrid indica rice (cv. Wuyou 1179) and then japonica (cv. Nipponbare). Single panicle weight, seed setting rate and 1000-kernel weight were reduced in the three infected varieties compared with healthy plants—by 85.42, 94.85 and 31.56% in Meixiangzhan; 52.43, 53.06 and 25.65% in Wuyou 1179 and 25.53, 49.32 and 23.86% in Nipponbare, respectively. Conclusions Our findings contribute basic data for field investigations, formulation of prevention and control strategies and further study of the pathogenesis of RSMV.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The noninvasive and accurate classification of NAFLD is still a challenging problem. In this study we proposed a new quantitative ultrasound (QUS) technique, which combined multiple QUS parameters for distinguishing steatosis stages. NAFLD was induced in the livers of 57 rats by gavage feeding with a high fat emulsion, while 8 rats were given a standard diet to serve as controls. Ex vivo ultrasound measurement was conducted for capturing the radiofrequency signal. Six QUS parameters were extracted and selected for linear combination. The results show that the overall performance of the combined parameter is better than that of the single QUS parameter. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) while using our proposed method to distinguish mild steatosis (stage S1) from the steatosis under stage S0 are 90.1%, 0.93, 0.88 and 0.97 respectively. In conclusion, the proposed method in this study can make up for the deficiency of single parameter and improve the quantitative staging ability of fatty liver, and thus could play an important role in the diagnosis of NAFLD.

Abstract Background The development and utilization of genetic markers play a pivotal role in marker-assisted breeding of rice cultivars during pyramiding of valuable genes. Among molecular markers, SNPs have become the most promising due to their wide distribution within genomes and suitability for high -throughput automated genotyping. Although metadata of SNPs have been identified via next generation sequencing in rice, a large gap between the development of SNP markers and the application in breeding still exists. To promote the application of SNP markers based on the KASP (Kompetitive Allele-Specific PCR) method in rice breeding, a set of core SNP arrays was built via the screening of SNP databases and literature resources based on the KASP method. Results Five hundred and ninety six SNPs classified into eight subsets including quality control, indica-indica variation, highly polymorphic, functional genes, key genes targeting sites, gene cloned region, important trait associated and gap filling sites were chosen to design KASP primers and 565 out of them were successfully designed, and the assay design success rate was 94.8%. Finally, 467 out of the 565 successfully-designed SNPs can display diversity at the loci were used to develop a set of core SNP arrays. To evaluate the application value of the core SNP markers in rice breeding, 481 rice germplasms were genotyped with three functional KASP markers designed from the sequences of GBSSI, SSIIa, and Badh2 from the core SNP arrays for estimation of their grain quality performance. Eighteen rice lines, including Xiangwanxian 13, Basmati 370, Ruanhua A, and PR 33319–9–1-1-5-3-5-4-1, harbor all three favorable alleles. The core KASP arrays were also used for rice germplasm assessment, genetic diversity and population evaluation. Four hundred and eighty-one rice germplasms were divided into 3 groups: POP1, POP2 and POP3. POP1 and POP2 were indica rice subgroups consisting of 263 and 186 rice germplasms, respectively. POP3 was a japonica rice subgroup consisting of 32 rice germplasms. The average F ST value for the three subgroups was 0.3501; the F ST value of POP1 and POP3 was the largest (0.5482), while that of POP1 and POP2 was the smallest (0.0721). The results showed that the genetic distance between the japonica and indica rice subspecies was large, indicating that the core SNP markers were effective at discriminating the population structure of the germplasms. Finally, the core KASP arrays were used for association analysis with milled grain traits. A total of 31 KASP markers were significantly associated (P

Based on the Hall effect, a magneto-acousto-electrical tomography (MAET) has been indicated to have a good ability for distinguishing the conductivity variations along the acoustic propagation direction, and B-scan imaging of the MAET is expected to obtain pathological information of the tissue. For achieving a clear B-scan image, in this paper, we designed and implemented a MAET system with a planar transducer and conducted a series of experiments to explore the characteristics of the magneto-acoustic-electrical (MAE) signal and electromagnetic interference (EMI) signal. The influence of the EMI signal on the MAE voltage signal was demonstrated experimentally, and the generation mechanism of the EMI signal was explained. Concurrently, several effective methods were proposed for reducing the EMI signal and improving the imaging resolution of the B-scan image. Additionally, for obtaining a B-scan image with high resolution, the detection front end was redesigned and algorithms applying the characteristics of the MAE signal were proposed. The accuracy, feasibility, and effectiveness of the improved methods were verified. Finally, a B-scan image was reconstructed with the relative amplitude of the conductivity. The results showed that: 1) the MAE signal obtained by the redesigned platform could be well separated from the EMI signal and had a higher SNR than that obtained by the previous detection system; 2) the proposed imaging algorithms had a high detection accuracy and achieved an axis resolution of 1 mm on the z-axis; and 3) the interfaces of the conductivity changes of homogeneous phantoms with 0.5% salinity were clearly presented by measuring the MAE wave packets, and the measured thicknesses of the phantoms were highly consistent with the actual thicknesses. This paper provides a theoretical and experimental basis for detecting the interface positions of conductivity variation, and the presented MAET technology is expected to become an alternative medical imaging modality for the early diagnosis and detection of biological cancerous tissues.

Fine-grained classification of cervical cells into different abnormality levels is of great clinical importance but remains very challenging. Contrary to the traditional classification methods that rely on hand-crafted or engineered features, convolution neural network (CNN) can classify cervical cells based on automatically learned deep features. However, CNN in previous studies does not involve cell morphological information, and it is unknown whether morphological features can be directly modeled by CNN to classify cervical cells. This paper presents a CNN-based method that combines cell image appearance with cell morphology for classification of cervical cells in Pap smear. The training of cervical cell dataset consists of adaptively re-sampled image patches coarsely centered on the nuclei. Several CNN models (AlexNet, GoogLeNet, ResNet, and DenseNet) pre-trained on ImageNet dataset were fine-tuned on the cervical dataset for comparison. The proposed method is evaluated on the Herlev cervical dataset by five-fold cross-validation at patient-level splitting. The results show that by adding cytoplasm and nucleus masks as raw morphological information into appearance-based CNN learning, higher classification accuracies can be achieved in general. Among the four CNN models, GoogLeNet fed with both morphological and appearance information obtains the highest classification accuracies of 94.5%, 71.3%, and 64.5%, for two-class (abnormal versus normal), four-class (“The Bethesda System”), and seven-class (“World Health Organization classification system”) classification tasks, respectively. Our method demonstrates that combining cervical cell morphology with appearance information can provide improved classification performance. Although the initial results are promising, deep learning-based fine-grained cervical cell classification remains a very challenging task for a high-precision diagnosis.

Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. It is mainly characterized by the absence of sperm in semen repeatedly or the number of sperm is small and not fully developed. At present, its pathogenesis remains largely unknown. The goal of this study is to identify hub genes that might affect biomarkers related to spermatogenesis. Using the clinically significant transcriptome and single-cell sequencing data sets on the Gene Expression Omnibus (GEO) database, we identified candidate hub genes related to spermatogenesis. Based on them, we performed Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses, protein-protein interaction (PPI) network analysis, principal component analysis (PCA), cell cluster analysis, and pseudo-chronological analysis. We identified a total of 430 differentially expressed genes, of which three have not been reported related to spermatogenesis (C22orf23, TSACC, and TTC25), and the expression of these three hub genes was different in each type of sperm cells. The results of the pseudo-chronological analysis of the three hub genes indicated that TTC25 was in a low expression state during the whole process of sperm development, while the expression of C22orf23 had two fluctuations in the differentiating spermatogonia and late primary spermatocyte stages, and TSACC showed an upward trend from the spermatogonial stem cell stage to the spermatogenesis stage. Our research found that the three hub genes were different in the trajectory of sperm development, indicating that they might play important roles in different sperm cells. This result is of great significance for revealing the pathogenic mechanism of NOA and further research.

Autophagy is a primary protective process that involves removing damaged organelles or dysfunctional proteins in eukaryotes. The autophagy pathway not only maintains cellular homeostasis, but also modulates the host's cellular response to pathogen infection. Several studies proved that autophagy plays a dominant role in plant fitness and immunity. As intracellular parasites, the replication and spread of viruses entirely rely upon the molecular machinery of the host cell, including the autophagy process. Plant viruses severely affect crop yields and quality. During infection, complex interactions occur between viral proteins and host factors in relation to plant defense and virus counter-defense. An increasing number of studies demonstrated that plants use autophagy to eliminate and inhibit viruses; some viruses were shown to manipulate the process of autophagy to promote their own replication and survival in plant cells. In this review, we summarize recent advances in plant autophagy, with an emphasis on the role of autophagy in plant virus infection.

Abstract Background The pathological or physiological changes of a crystalline lens directly affect the eye accommodation and transmittance, and then they increase the risk of presbyopia and cataracts for people in the middle and old age groups. There is no universally accepted quantitative method to measure the lens' mechanical properties in vivo so far. This study aims to investigate the possibility of assessing the age-related stiffness change of crystalline lens by acoustic-radiation-force-based ultrasound elastography (ARF-USE) in a rabbit model in vivo. Methods There were 13 New Zealand white rabbits that were divided into four groups and fed normally until they were 60 (n = 4), 90 (n = 2), 120 (n = 4), and 150 (n = 3) days old, respectively. An ARF-USE platform was built based on the Verasonics™ Vantage 256 system. The shear waves were excited and traced in the lens by a linear ultrasound probe after a rabbit was anaesthetized. Results The average group velocities were 1.38 ± 0.2 m/s, 2.06 ± 0.3 m/s, 2.07 ± 0.29 m/s, and 2.30 ± 0.28 m/s, respectively, for the four groups of rabbits. The results shows that the group velocity has a strong correlation with the day age (r = 0.84, p < 1 × 10−7) and the weight (r = 0.83, p < 1×10−7) of the rabbits while the maximum displacement has no correlations with the day age (r = 0.27, p > 0.1) and the weight (r = 0.32, p > 0.1). Conclusion This study demonstrated that the group velocity measured by ARF-USE had a strong correlation with age-related stiffness in a rabbit model, suggesting that group velocity is a good biomarker to characterize the stiffness of a crystalline lens. This study also demonstrated the feasibility of using this USE technique to assess the mechanical properties of the lens in vivo for clinical or research purposes.

As a non-invasive and hybrid imaging modality, magneto-acoustic-electrical tomography (MAET) is extremely useful for the electrical conductivity measurement in vivo. Based on the Verasonics system and the MC600 displacement platform, we designed and implemented a novel MAET system with a chirp pulse stimulation (MAET-CPS) method for electrical conductivity measurement. In the system, a 2-3 MHz chirp signal was exploited for stimulating ultrasound power probe. Then, the interface positions of conductivity variation were obtained by digital demodulation of the excitation signal and the received voltage signal. Finally, five different homogeneous phantoms with same size were used to investigate the feasibility, accuracy, and repeatability of MAET-CPS. The results showed that: 1) when a chirp signal with pulse duration of 1000 μs was used to stimulate a homogeneous phantom with 0.5% NaCl, the reconstructed B-scan image of the conductivity distribution was highly consistent with the ultrasound B-scan imaging and physical size; 2) the signal-to-noise ratio of the system and the detection resolution of the interface of conductivity variations could be influenced by the linear frequency modulation period. The resolution obtained by using chirp signal with pulse duration of 1000 μs was better than that of 500 μs and 1500 μs; and 3) the interfaces of conductivity variations of homogeneous phantoms with five different concentrations (0.4%, 0.5%, 0.6%, 0.7%, and 0.8%) were clearly presented and the measured thicknesses of each phantom showed good agreement with the thickness of the target sample. This paper has laid the foundation for the MAET-CPS modality in the phantom sample, and MAET-CPS is expected to become an alternative imaging method for early diagnosis and detection of biological cancerous tissues.

Abstract Background Ultrasound transient elastography technology has found its place in elastography because it is safe and easy to operate. However, it’s application in deep tissue is limited. The aim of this study is to design an ultrasound transient elastography system with coded excitation to obtain greater detection depth. Methods The ultrasound transient elastography system requires tissue vibration to be strictly synchronous with ultrasound detection. Therefore, an ultrasound transient elastography system with coded excitation was designed. A central component of this transient elastography system was an arbitrary waveform generator with multi-channel signals output function. This arbitrary waveform generator was used to produce the tissue vibration signal, the ultrasound detection signal and the synchronous triggering signal of the radio frequency data acquisition system. The arbitrary waveform generator can produce different forms of vibration waveform to induce different shear wave propagation in the tissue. Moreover, it can achieve either traditional pulse-echo detection or a phase-modulated or a frequency-modulated coded excitation. A 7-chip Barker code and traditional pulse-echo detection were programmed on the designed ultrasound transient elastography system to detect the shear wave in the phantom excited by the mechanical vibrator. Then an elasticity QA phantom and sixteen in vitro rat livers were used for performance evaluation of the two detection pulses. Results The elasticity QA phantom’s results show that our system is effective, and the rat liver results show the detection depth can be increased more than 1 cm. In addition, the SNR (signal-to-noise ratio) is increased by 15 dB using the 7–chip Barker coded excitation. Conclusions Applying 7-chip Barker coded excitation technique to the ultrasound transient elastography can increase the detection depth and SNR. Using coded excitation technology to assess the human liver, especially in obese patients, may be a good choice.

The aim of the study is to screen the significant sonographic features by logistic regression analysis and fit a model to diagnose thyroid nodules. A total of 525 pathological thyroid nodules were retrospectively analyzed. All the nodules underwent conventional ultrasonography (US), strain elastosonography (SE), and contrast -enhanced ultrasound (CEUS). Those nodules' 12 suspicious sonographic features were used to assess thyroid nodules. The significant features of diagnosing thyroid nodules were picked out by logistic regression analysis. All variables that were statistically related to diagnosis of thyroid nodules, at a level of p < 0.05 were embodied in a logistic regression analysis model. The significant features in the logistic regression model of diagnosing thyroid nodules were calcification, suspected cervical lymph node metastasis, hypoenhancement pattern, margin, shape, vascularity, posterior acoustic, echogenicity, and elastography score. According to the results of logistic regression analysis, the formula that could predict whether or not thyroid nodules are malignant was established. The area under the receiver operating curve (ROC) was 0.930 and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 83.77%, 89.56%, 87.05%, 86.04%, and 87.79% respectively.

Ultrasound microbubble combined optic protection drugs have obvious protective effect on optic nerve damage. This way of targeting drug delivery is becoming more simple, not through the whole body metabolism, avoiding drug via blood circulation when facing the decomposition and the environment in the interference and destruction process of drugs, to maximize the guarantee to reach target organs of drug concentration and to reache the maximum therapeutic effect. The technique of ultrasound microbubbles is safe, controllable, nonimmunogenic, and repeatable. It provides us with a novel idea in the administration of neuroprotective drugs.

As magneto-acoustic-electrical tomography (MAET) combines the merits of high contrast and high imaging resolution, and is extremely useful for electrical conductivity measurement, so it is expected to be a promising medical imaging modalities for diagnosis of early-stage cancer. Based on the Verasonics system and the MC600 displacement platform, we designed and implemented a MAET system with a chirp pulse stimulation (MAET-CPS) method and a focal probe was utilized for stepscan focus excitation to enhance the imaging resolution. The relevant experiments were conducted to explore the influence of excitation positions of the single-focus point, and the effect of the excitation position on the amplitudes of the conductivity variation was clearly demonstrated. In order to take advantage of the merits of multifocus imaging, we firstly proposed a single focus MAET system with a chirp pulse stimulation (sfMAET-CPS) method and a multifocus MAET system with a chirp pulse stimulation (mfMAET-CPS) method for high-resolution conductivity imaging, and a homogenous gelatin phantom with a cuboid-shaped hole was used to investigate the accuracy of mfMAET-CPS. Comparative experiments were carried out on the same uniform phantom by the sfMAET-CPS and the mfMAET-CPS, respectively. The results showed that: (1) the electrical conductivity distributions of the homogenous phantom with a cuboid-shaped hole were detected by the sfMAET-CPS but were easily affected by the focal point, which demonstrated that the sfMAET-CPS had a low imaging resolution. (2) Compared with the sfMAET-CPS, the imaging effect of the mfMAET-CPS was much better than that of the sfMAET-CPS. (3) A linear interpolation algorithm was used to process the 2D conductivity distribution; it increased the smoothness of the conductivity distribution and improved the imaging effect. The stepscan focus excitation and the linearly frequency-modulated theory provide an alternative scheme for the clinical application of MAET.

Acquisition of the standard plane is the prerequisite of biometric measurement and diagnosis during the ultrasound (US) examination. In this paper, a new algorithm is developed for the automatic recognition of the fetal facial standard planes (FFSPs) such as the axial, coronal, and sagittal planes. Specifically, densely sampled root scale invariant feature transform (RootSIFT) features are extracted and then encoded by Fisher vector (FV). The Fisher network with multi-layer design is also developed to extract spatial information to boost the classification performance. Finally, automatic recognition of the FFSPs is implemented by support vector machine (SVM) classifier based on the stochastic dual coordinate ascent (SDCA) algorithm. Experimental results using our dataset demonstrate that the proposed method achieves an accuracy of 93.27% and a mean average precision (mAP) of 99.19% in recognizing different FFSPs. Furthermore, the comparative analyses reveal the superiority of the proposed method based on FV over the traditional methods.

T-rays is sensitive to covalently cross-linked proteins and can be used to probe unique dynamic properties of water surrounding a protein. In this paper, we demonstrate the unique absorption properties of the dynamic hydration shells determined by hemagglutinin (HA) protein in terahertz frequency. We study the changes arising from different concentrations in detail and show that nonlinear absorption coefficient is induced by the dynamic hydration water. The binary and ternary component model were used to interpret the nonlinearity absorption behaviors and predict the thickness of the hydration shells around the HA protein in aqueous phase.

The purpose of ultrasound elastography is to identify lesions by reconstructing the hardness characteristics of tissue reconstructed from ultrasound data. Conventional quasi-static ultrasound elastography is easily applied to obtain axial strain components along the compression direction, with the results inverted to represent the distribution of tissue hardness under the assumption of constant internal stresses. However, previous works of quasi-static ultrasound elastography have found it difficult to obtain the lateral and shear strain components, due to the poor lateral resolution of conventional ultrasound probes. The physical nature of the strain field is a continuous vector field, which should be fully described by the axial, lateral, and shear strain components, and the clinical value of lateral and shear strain components of deformed tissue is gradually being recognized by both engineers and clinicians. Therefore, a biomechanical-model-constrained filtering framework is proposed here for recovering a full displacement field at a high spatial resolution from the noisy ultrasound data. In our implementation, after the biomechanical model constraint is integrated into the state-space equation, both the axial and lateral displacement components can be recovered at a high spatial resolution from the noisy displacement measurements using a robust H∞ filter, which only requires knowledge of the worst-case noise levels in the measurements. All of the strain components can then be calculated by applying a gradient operator to the recovered displacement field. Numerical experiments on synthetic data demonstrated the robustness and effectiveness of our approach, and experiments on phantom data and in-vivo clinical data also produced satisfying results.

The GP2 peptide is derived from the Human Epidermal growth factor Receptor 2 (HER2/nue), a marker protein for breast cancer present in saliva. In this paper we study the temperature dependent behavior of hydrated GP2 at terahertz frequencies and find that the peptide undergoes a dynamic transition between 200 and 220 K. By fitting suitable molecular models to the frequency response we determine the molecular processes involved above and below the transition temperature (T(D)). In particular, we show that below T(D) the dynamic transition is dominated by a simple harmonic vibration with a slow and temperature dependent relaxation time constant and that above T(D), the dynamic behavior is governed by two oscillators, one of which has a fast and temperature independent relaxation time constant and the other of which is a heavily damped oscillator with a slow and temperature dependent time constant. Furthermore a red shifting of the characteristic frequency of the damped oscillator was observed, confirming the presence of a non-harmonic vibration potential. Our measurements and modeling of GP2 highlight the unique capabilities of THz spectroscopy for protein characterization.