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Ramie fibers, one of the most important natural fibers in China, are mainly composed of lignin, cellulose, and hemicellulose. As the high lignin content in the fibers results in a prickly texture, the lignin content is deemed to be an important trait of the fiber quality. In this study, the genetic basis of the fiber lignin content was evaluated, resulting in the identification of five quantitative trait loci (QTLs). Three genes, whole_GLEAN_10021050, whole_GLEAN_10026962, and whole_GLEAN_10009464 that were identified on the QTL regions of qLC7, qLC10, and qLC13, respectively, were found to be homologs of the Arabidopsis lignin biosynthetic genes. Moreover, all three genes displayed differential expression in the barks located in the top and middle parts of the stem, where lignin was not being synthesized and where it was being biosynthesized, respectively. Sequence comparison found that these three genes had wide variations in their coding sequences (CDSs) and putative promoter regions between the two parents, especially the MYB gene whole_GLEAN_10021050, whose protein had insertions/deletions of five amino acids and substitutions of two amino acids in the conserved domain. This evidence indicates that these three genes are potentially involved in lignin biosynthesis in ramie fibers. The QTLs identified from this study provide a basis for the improvement of lignin content and fiber quality in ramie breeding. The characterization of the three candidate genes here will be helpful for the future clarification of their functions in ramie. [ABSTRACT FROM AUTHOR]

Aim: To elucidate the safety and visual quality of implantable collamer lens with central hole (ICL V4c) implantation for correcting moderate and high myopia for at least 5y., Methods: This retrospective study was conducted on 58 patients (114 eyes) who were followed up for at least 5y after ICL V4c implantation. The observation was done before and on 1d, 1mo, 1 and 5y or more after the surgical procedure. The visual acuity, subjective refraction, intraocular pressure, vault, axial length, central hole position, pupil diameter, visual quality, and adverse events were analyzed. The visual quality includes aberration, the modulation transfer function cutoff frequency (MTF cutoff), objective scattering index (OSI), Stroller's ratio (SR), and visual quality questionnaire., Results: The average follow-up period was 69.25±3.80mo (range 60-82mo) and the preoperative spherical equivalent (SE) was -8.66±1.97 D. At 5y after operation, the safety index was 1.01±0.02 and the efficacy index was 0.99±0.42 and SE was -0.65±0.63 D. The 59.6% of the eyes achieved an uncorrected distance visual acuity of 20/20, 76.3% of the eyes had SE within ±1.0 D at the last visit. The axial length increased by 0.29±0.71 mm 5y after the surgery ( t =-3.843, P <0.001). The mean vault at the last follow-up was 510.59±245.61 µm. The central hole was on the temporal side in 80 eyes (84.2%). The visual quality questionnaire showed that 98.2% patients were satisfied with the surgical procedure. Adverse events occurred in 4 eyes (3.5%), including the posttraumatic toric ICL rotation (2 eyes), iris incarceration (1 eye), and posttraumatic ICL displacement (1 eye) at the last follow-up., Conclusion: Long-term ICL V4c implantation is safe, effective, and stable for correcting moderate and to high myopia, and the visual quality with patients is excellent and satisfactory, but the progression of axial length still needs attention after surgery., (International Journal of Ophthalmology Press.)

Phage therapy has re-emerged as a promising solution for combating antimicrobial-resistant bacterial infections. Increasingly, studies have revealed that phages possess therapeutic potential beyond their antimicrobial properties, including regulating the gut microbiome and maintain intestinal homeostasis, as a novel nanocarrier for targeted drug delivery. However, the complexity and unpredictability of phage behavior during treatment pose a significant challenge in clinical practice. The intricate interactions established between phages, humans, and bacteria throughout their long coexistence in the natural ecosystem contribute to the complexity of phage behavior in therapy, raising concerns about their efficacy and safety as therapeutic agents. Revealing the mechanisms by which phages interact with the human body will provide a theoretical basis for increased application of promising phage therapy. In this review, we provide a comprehensive summary of phage-mammal interactions, including signaling pathways, adaptive immunity responses, and phage-mediated anti-inflammatory responses. Then, from the perspective of phage-mammalian immune system interactions, we present the first systematic overview of the factors affecting phage therapy, such as the mode of administration, the physiological status of the patient, and the biological properties of the phage, to offer new insights into phage therapy for various human diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

The Lamb wave reciprocity-based method is an effective candidate for the health monitoring of composite plates. However, if the damage is located symmetrically between the transmitter-receiver pair, the reciprocity still holds true and the method misjudges its presence. In the present work, a new method for computing the reciprocity index (RI) from Lamb wave signals with extended data length is proposed. This method exploits extra indirect waves that bounce one or more times between the damage and other reflectors. These waves probe the damage through different paths and from different directions. Thus, the damage missed by the direct wave may be exposed by the indirect waves. Benefiting from that, two modified RIs are defined and their performance is validated by two experimental examples. As expected, both indices demonstrate excellent sensitivity to damage even in the middle of the transmitter-receiver pair and ensure a low threshold for the pristine condition, illustrating an excellent ability to distinguish between health and illness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To alleviate the mechanical instability of major shear bands in metallic glasses at room temperature, topologically heterogeneous structures were introduced to encourage the multiplication of mild shear bands. Different from the former attention on topological structures, here we present a compositional design approach to build nanoscale chemical heterogeneity to enhance homogeneous plastic flow upon both compression and tension. The idea is realized in a Ti-Zr-Nb-Si-XX/Mg-Zn-Ca-YY hierarchically nanodomained amorphous alloy, where XX and YY denote other elements. The alloy shows ~2% elastic strain and undergoes highly homogeneous plastic flow of ~40% strain (with strain hardening) in compression, surpassing those of mono- and hetero-structured metallic glasses. Furthermore, dynamic atomic intermixing occurs between the nanodomains during plastic flow, preventing possible interface failure. Our design of chemically distinct nanodomains and the dynamic atomic intermixing at the interface opens up an avenue for the development of amorphous materials with ultrahigh strength and large plasticity., (© 2023. The Author(s).)

Famitinib is a tyrosine kinase inhibitor under clinical investigation for the treatment of solid tumors. Here, a 3-period crossover trial investigated the effect of high-fat or low-fat food intake on the single-dose pharmacokinetic properties of oral famitinib. Twenty-four healthy Chinese participants were enrolled and received a single 25-mg dose of famitinib malate capsule following a high-fat or low-fat breakfast before dosing. Blood samples were collected before dosing (0 hour) to 192 hours after dosing, and famitinib concentrations in plasma were determined with validated liquid chromatography-tandem mass spectrometry. Compared with the fasting condition, the geometric mean ratios for low-fat/fasting were 98.6%, 107.7%, and 107.5% for maximum plasma concentration, area under the plasma concentration-time curve (AUC) over the dosing interval, and AUC from time 0 to infinity, respectively. Those for high-fat/fasting were 84.4%, 105.0%, and 105.1% for maximum plasma concentration, AUC over the dosing interval, and AUC from time 0 to infinity, respectively. There was no significant difference in adverse events between fasting and fed conditions, and no serious adverse events occurred during the trial. In conclusion, oral famitinib bioavailability is not affected by food intake, implying that patients with cancer do not need to consider dietary status when using famitinib. This is considered important for convenience and treatment compliance., (© 2023, The American College of Clinical Pharmacology.)

Objective: To investigate the clinical efficacy and prognostic factors of transnasal endoscopic optic decompression in the treatment of traumatic optic neuropathy (TON)., Methods: A retrospective analysis was performed on 13 TON patients in The Seventh Affiliated Hospital of Sun Yat-sen University and Shenzhen Eye Hospital in Shenzhen City (China) from June 2020 to April 2022. These patients had received transnasal endoscopic optic decompression, and hormonal and neurotrophic drugs were given after surgery. Visual acuity (VA) improvement was used as the criterion to judge clinical efficacy., Results: In a total of 13 patients, 13 injured eyes (12 men and 1 woman; mean age, 28.0 ± 11.8 years) received transnasal endoscopic optic decompression. After surgery, nine patients had improved VA, whereas four patients failed to show any improvement, resulting in a total effective rate of 69.2%. Of the six patients with no light perception preoperatively, three had effective results after the operation, giving an effective rate of 50.0%. Of the seven patients with residual light sensation preoperatively, six had effective results after the operation, giving an effective rate of 85.7%. Of the 10 patients operated on within 7 days after injury, seven had effective results, giving an effective rate of 70%. Of the three patients injured and operated on after 7 days, two had effective results, giving an effective rate of 66.7%., Conclusion: Transnasal endoscopic optic nerve decompression is an effective treatment method for TON. The presence of residual light perception and the timing of surgery within 7 days are crucial to the prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tu, Xiong, Qi, Ou, Rao, Sun, Fan and Liu.)

Accurate detection and characterization of defects in high-density polyethylene (HDPE) pipe materials are very important in assessing the structural integrity of critical structures in the nuclear industry. One specific challenge here is the presence of the viscoelastic attenuation of this material, which can lead to resolution degradation and loss of detail in ultrasound imaging. In this work, an effective ultrasonic imaging technique using the least-squares reverse time migration with preconditioned stochastic gradient descent (LSRTM-PSGD) is developed to improve image quality. Compared with standard ultrasonic imaging methods which only consider the direct ray path of ultrasound, least-squares reverse time migration (LSRTM) is a powerful wave-equation-based approach and it has the ability to account for rapid spatial velocity variations and to utilize all wavefield information. The LSRTM is an inversion method, which iteratively updates the reflectivity model by minimizing the modeled data and measured data. The proposed LSRTM-PSGD combines the advantages of stochastic gradient descent (SGD) and adaptive learning rate. The SGD updates the parameter on each transmitter and the fluctuation of SGD can enable it to reach a better minimum, thus improving the imaging quality. Compared with the conventional LSRTM algorithm using a fixed step size, the proposed LSRTM-PSGD algorithm can use the adaptive moment estimation to calculate the adaptive learning rate for the parameter, thereby updating the parameter appropriately. The performance of the LSRTM-PSGD algorithm is tested with experimental data. The results show high-quality reconstructed images with good resolution for defect identification in HDPE pipe materials, especially for deep defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Porcine respiratory disease complex (PRDC) is a serious disease caused by multiple pathogens which inflicts huge economic losses on the pig industry. Investigating the epidemiology of porcine respiratory bacterial pathogens (PRBPs) in specific geographic areas and exploring the antibiotic susceptibility of local strains will contribute to the prevention and control of PRDC. However, the epidemiology of PRBPs in Guangxi Province remains unclear, and existing diagnostic methods have multiple limitations, such as high costs and the detection of only a single pathogen at a time. In this study, we developed a multiplex PCR assay for Streptococcus suis, Glaesserella parasuis, Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma hyopneumoniae, and investigated the prevalence of PRBPs in pigs with respiratory symptoms in Guangxi Province. The isolates from positive samples were subjected to susceptibility tests to 16 antibiotics. Our results indicated that of the 664 samples from pigs with respiratory symptoms, 433 (65.21%), 320 (48.19%), 282 (42.47%), 23 (3.46%), and 9 (1.36%), respectively, carried each of these 5 pathogens; 533 samples were positive; and 377 (56.78%) carried multiple pathogens simultaneously. The dominant PRBPs in pigs with respiratory symptoms in Guangxi province were S. suis, G. parasuis, and A. pleuropneumoniae, which frequently co-infected swine herds. Most of the isolates (A. pleuropneumoniae, G. parasuis, S. suis, and P. multocida) were sensitive to cefquinome, ceftiofur, trimethoprim-sulfamethoxazole (TMP-SMX), and tiamulin antibiotics. We developed a rapid specific multiplex PCR assay for PRBPs. Our findings provide new information on the epidemiology of PRBPs in Guangxi Province and offer a reference for developing drug targets against PRDC. IMPORTANCE Pigs are closely associated with humans as the most common food animals and the vectors of numerous pathogens. PRDC, caused by multiple pathogens, is a serious disease that can cause growth retardation in swine and even sudden death. Due to the droplet transmission of PRBP and the similar clinical signs of different pathogen infections, most pig farms struggle to identify and control PRBPs, leading to the abuse of antibiotics. In addition, some PRBPs have the potential to infect humans and threaten human health. Therefore, this study developed a multiplex PCR method targeting PRBPs, investigated the prevalence of these pathogens, and tested their antibiotic susceptibility. Our studies have important implications for public health safety and the development of the pig industry.

Introduction: Objective, accurate, and efficient measurement of exophthalmos is imperative for diagnosing orbital diseases that cause abnormal degrees of exophthalmos (such as thyroid-related eye diseases) and for quantifying treatment effects. Methods: To address the limitations of existing clinical methods for measuring exophthalmos, such as poor reproducibility, low reliability, and subjectivity, we propose a method that uses deep learning and image processing techniques to measure the exophthalmos. The proposed method calculates two vertical distances; the distance from the apex of the anterior surface of the cornea to the highest protrusion point of the outer edge of the orbit in axial CT images and the distance from the apex of the anterior surface of the cornea to the highest protrusion point of the upper and lower outer edges of the orbit in sagittal CT images. Results: Based on the dataset used, the results of the present method are in good agreement with those measured manually by clinicians, achieving a concordance correlation coefficient (CCC) of 0.9895 and an intraclass correlation coefficient (ICC) of 0.9698 on axial CT images while achieving a CCC of 0.9902 and an ICC of 0.9773 on sagittal CT images. Discussion: In summary, our method can provide a fully automated measurement of the exophthalmos based on orbital CT images. The proposed method is reproducible, shows high accuracy and objectivity, aids in the diagnosis of relevant orbital diseases, and can quantify treatment effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Rao, Wu, Zhou, Liu and Zhang.)

Objective: Microelectrode recording (MER) guided subthalamic nucleus deep brain stimulation (STN-DBS) under local anesthesia (LA) is widely applied in the management of advanced Parkinson's disease (PD). Whereas, awake DBS under LA is painful and burdensome for PD patients. We analyzed the influence of general anesthesia (GA) on intraoperative MER, to assess the feasibility and effectiveness of GA in MER guided STN-DBS., Methods: Retrospective analysis was performed on the PD patients, who underwent bilateral MER guided STN-DBS in Wuhan Union Hospital from July 2019 to December 2021. The patients were assigned to LA or GA group according to the anesthetic methods implemented. Multidimensional parameters, including MER signals, electrode implantation accuracy, clinical outcome and adverse events, were analyzed., Results: A total of 40 PD patients were enrolled in this study, including 18 in LA group and 22 in GA group. There were no statistically significant differences in patient demographics and baseline characteristics between two groups. Although, the parameters of MER signal, including frequency, inter-spike interval (ISI) and amplitude, were obviously interfered under GA, the waveforms of MER signals were recognizable and shared similar characteristics with LA group. Both LA and GA could achieve effective electrode implantation accuracy and clinical outcome. They also shared similar adverse events postoperatively., Conclusion: GA is viable and comparable to LA in MER guided STN-DBS for PD, regarding electrode implantation accuracy, clinical outcome and adverse events. Notably, GA is more friendly and acceptable to the patients who are incapable of enduring intraoperative MER under LA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qian, Wang, Rao, Zhang, Sun, Hu, Hao, Jiang and Fu.)

Bacterial defense barriers, such as DNA methylation-associated restriction-modification (R-M) and the CRISPR-Cas system, play an important role in bacterial antimicrobial resistance (AMR). Recently, a novel R-M system based on DNA phosphorothioate (PT) modification has been shown to be widespread in the kingdom of Bacteria as well as Archaea . However, the potential role of the PT R-M system in bacterial AMR remains unclear. In this study, we explored the role of PT R-Ms in AMR with a series of common clinical pathogenic bacteria. By analyzing the distribution of AMR genes related to mobile genetic elements (MGEs), it was shown that the presence of PT R-M effectively reduced the distribution of horizontal gene transfer (HGT)-derived AMR genes in the genome, even in the bacteria that did not tend to acquire AMR genes by HGT. In addition, unique gene variation analysis based on pangenome analysis and MGE prediction revealed that the presence of PT R-M could suppress HGT frequency. Thus, this is the first report showing that the PT R-M system has the potential to repress HGT-derived AMR gene acquisition by reducing the HGT frequency. IMPORTANCE In this study, we demonstrated the effect of DNA PT modification-based R-M systems on horizontal gene transfer of AMR genes in pathogenic bacteria. We show that there is no apparent association between the genetic background of the strains harboring PT R-Ms and the number of AMR genes or the kinds of gene families. The strains equipped with PT R-M harbor fewer plasmid-derived, prophage-derived, or integrating mobile genetic element (iMGE)-related AMR genes and have a lower HGT frequency, but the degree of inhibition varies among different bacteria. In addition, compared with Salmonella enterica and Escherichia coli, Klebsiella pneumoniae prefers to acquire MGE-derived AMR genes, and there is no coevolution between PT R-M clusters and bacterial core genes.

In this study, the drug-loading and antibacterial activity of carbodiimide/N-hydroxysuccinimide (EDC/NHS) crosslinked decellularized lenticules (CDLs) were evaluated. Small incision lenticule extraction derived lenticules were decellularized and modified with crosslinking concentrations of 0.00 (E/L00, non-crosslinked), 0.01 (E/L01), 0.05 (E/L05) and 0.25 mmol (E/L25) EDC per mg lenticules at 5:1 EDC/NHS ratios with non-decellularized non-crosslinked lenticules (NDLs) as controls. NDLs and EDC/NHS CDLs had similar water contents. The light transmittance percentages (400-800 nm) were 91.55 ± 1.16%, 88.68 ± 1.19%, 80.86 ± 1.94%, 85.12 ± 2.42% and 85.62 ± 2.84% for NDLs, E/L00, E/L01, E/L05 and E/L25, respectively ( P < 0.01). The EDC/NHS CDLs (diameter: 6.36 ± 0.18 mm; central thickness: 117.31 ± 3.46 μm) were soaked in 3% (wt./vol.) levofloxacin (LEV) solution for 3 h. The drug release concentrations of LEV-impregnated EDC/NHS CDLs were determined by high-performance liquid chromatography. Zone inhibition (ZOI) against Staphylococcus aureus of E/L01, E/L05 and E/L25 were superior to E/L00 CDLs ( P < 0.01) and among the different crosslinked groups, E/L05 lenticules produced the largest ZOIs and their drug concentration release over 21 d was the highest. EDC/NHS crosslinking can improve the drug-loading effect and antibacterial activity of decellularized lenticules. LEV-impregnated EDC/NHS CDLs are promising drug delivery carriers., (© 2023 IOP Publishing Ltd.)

With the increasing use of high density polyethylene (HDPE) pipes in nuclear industry which puts safety at the forefront, ultrasonic array imaging methods play a vital role in the structural integrity of HDPE pipe materials. However, the viscoelastic attenuation of HDPE pipe materials significantly decreases the level of signals, leading to a low signal-to-noise ratio caused by electronic noise. In this work, a domain-adapted spatio-temporal singular value decomposition (STSVD) processing algorithm combined with the total focusing method is proposed to improve the ultrasonic array image quality. First, the real-valued radio frequency (RF) data or A-scan signals are demodulated into the complex analytic signals containing in-phase and quadrature (I/Q) components. Then, the STSVD processing algorithm is used to filter the I/Q data, and the filtered I/Q data is converted into RF signals. Finally, the total focusing method is applied to the processed RF signals to produce the image of the region under detection as a stage of post-processing. Experiments are carried out with an ultrasonic linear phased array in contact with the HDPE pipe materials containing multiple side-drilled holes and through-wall notches. Results show that the proposed method can produce images with high quality to provide good inspection and characterization of defects in highly attenuative materials, especially the deeper defects., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To explore the internal mechanism of hepatocellular carcinoma (HCC) induced by chronic hepatitis B virus (HBV) infection., Methods: L02, HepG2 and Huh7 cells stably overexpressing HBV preS1 antigen were analyzed by flow cytometry, qRT-PCR and tumorigenesis in nude mice to evaluate the effect of preS1 antigen in HBV-related hepatocarcinogenesis., Results: Our results showed that the expression of cancer stem cell (CSCs) related factors and cell surface markers in preS1 overexpressing cells were up-regulated, and the tumorigenicity of these cells was enhanced in nude mice. In addition, preS1 overexpression could down-regulate the expression of major histocompatibility complex Ⅰ (MHC-Ⅰ). The expression of MHC-Ⅰ on the cell surface could be restored by adding interferon gamma (IFN-γ) in the process of cell culturing and the tumorigenicity of cells in nude mice could thus be reduced., Conclusion: Based on the above results, we believe that preS1 is a carcinogen of HBV and that it promotes the formation of liver cancer through down regulating MHC-Ⅰ on the surface of hepatocytes., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: The efficacy and safety of deep brain stimulation (DBS) under general anesthesia for the treatment of dystonia have not yet been confirmed with high level of evidence. This meta-analysis with pooled individual patient data aims to assess the clinical outcomes and identify the potential prognostic factors of dystonia patients who underwent general anesthesia DBS., Methods: We searched PubMed, Web of Science, and Embase for articles describing patients with dystonia who underwent asleep DBS and had individual Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores. The relative improvement in BFMDRS scores was considered the primary outcome. Pearson correlation analyses and multivariate linear regression analysis were conducted to explore the prognostic factors., Results: A total of 34 studies involving 341 patients were included. The mean postoperative improvement in BFMDRS-M (BFMDRS movement subscale) and BFMDRS-D (BFMDRS disability subscale) scores were 58.6±36.2% and 48.5±38.7% at the last follow-up visit, respectively, with a mean follow-up time of 22.4±27.6 months. Age at surgery and disease duration showed a negative correlation with the percent improvement of BFMDRS-M (%) at the last visit (r=-0.134, P=0.013; r=-0.165, P=0.006). In the stepwise multivariate regression, only disease duration remained a relevant factor. Additionally, the adverse events were acceptable., Conclusion: General anesthesia DBS is a safe, effective, and feasible option for dystonia patients in the long term. Shorter disease duration predicts better clinical outcomes.

This paper presented a novel ultrasonic wireless power link (UWPL) to provide power supply for embedded condition monitoring of enclosed metallic structures, where recharging or replacing batteries can be problematic. Two piezoelectric transducers are adopted to establish the wireless power links, within which one transducer is used to generate ultrasonic waves and the other is to receive the transferred ultrasonic energy and to energize the associated embedded condition monitoring units. A power management solution is established to regulate the receiver output into a constant voltage suitable for sensing application. A theoretical model was established to understand the UWPL dynamics and to analyze the energy budget balance between the UWPL and the sensing power demands. A finite element model was built to validate the proposed idea. The UWPL was then experimentally implemented using two piezoelectric transducers and tested in aluminium plates with different thickness. A power management sub-system was developed and tested for sensing applications. An output power of 1.73 mW was obtained on a 1.5 kΩ resister with the input voltage of 15 V at 42.6 kHz through a 6 mm-thick aluminium plate. Sufficient power can be transferred over a large distance via metallic structures, showing the capability in implementing battery-free condition monitoring of enclosed metallic structures, such as petroleum pipelines, engines, and aluminium airframe., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A non-catalytic, mild, and easy-to-handle protecting group switched 1,3-dipolar cycloaddition (1,3-DC) between bi- or mono-N-protected Dha and C,N-cyclic azomethine imines, which afford various quaternary amino acids with diverse scaffolds, is disclosed. Specifically, normal-electron-demand 1,3-DC reaction occurs between bi-N-protected Dha and C,N-cyclic azomethine imines, while inverse-electron-demand 1,3-DC reaction occurs between mono-N-protected Dha and C,N-cyclic azomethine imines. Above all, the reactions can be carried out between peptides with Dha residues at the position of interest and C,N-cyclic azomethine imines, both in homogeneous phase and on resins in SPPS. It provides a new toolkit for late-stage peptide modification, labeling, and peptide-drug conjugation. To shed light on the high regioselectivity of the reaction, DFT calculations were carried out, which were qualitatively consistent with the experimental observations., (© 2020 Wiley-VCH GmbH.)

Objective: Deep brain stimulation (DBS) is considered an effective and safe treatment for patients with primary Meige syndrome (MS). Both the subthalamic nucleus (STN) and globus pallidus pars internus (Gpi) have been shown to be optional targets for electrode implantation to improve clinical symptoms, but the relationship between clinical outcomes and target is still unclear. The current study aims to compare the clinical outcomes of DBS with different electrode targets for primary MS., Materials and Methods: We performed a retrospective study to assess the clinical outcomes for 17 consecutive patients with primary MS in Wuhan Union Hospital from January 2016 to September 2019. Six patients were treated by Gpi-DBS and 11 patients were treated by STN-DBS. All patients were assessed before surgery and at the last follow-up after surgery. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) including the movement and disability scales was used to evaluate the dystonia severity of the eyes, the mouth, speech, and swallowing. The median follow-up duration was 30.1 ± 13.1 months (range 6 months-52 months)., Results: In our study, DBS improved the BFMDRS-M scores by 70.52 ± 7.45% and the BFMDRS-D scores by 70.51 ± 8.38% for patients with MS. STN-DBS and Gpi-DBS had similar effects not only on the BFMDRS-M and BFMDRS-D scores, but also on the subitems including eyes, mouth, speech, and swallowing. The stimulation voltage for the Gpi was significantly higher than that for the STN. The improvements were similar in the general anesthesia and local anesthesia groups (p > 0.05)., Conclusion: The curative effects of STN-DBS and Gpi-DBS on patients with primary MS are similar. Both the STN and Gpi could be effective targets of DBS for primary MS., (© 2020 International Neuromodulation Society.)

In this paper, an ultrasonic tomography method based on acoustic multi-parameter full waveform inversion (FWI) is developed for high-resolution reconstructions of velocity and density in metal components. The challenging issue in multi-parameter FWI is to deal with the trade-off effects between different parameters of different natures. Moreover, different parameters have different orders of amplitudes in the wave-field which make the inversion ill-conditioned. The inverse Hessian has been shown to mitigate the coupling effects and rescale the amplitudes of different parameters, and then the reliable updates of different parameters are available. The simultaneous reconstructions of velocity and density by using the truncated Gauss-Newton method, in which the inverse Hessian can be considered through a matrix-free conjugate gradient solution of the Gauss-Newton normal equation, are investigated by simulation as well as experiment on the centred inclusions. The results show that this method can effectively alleviate the trade-off effects between velocity and density, and thus the velocity of the inclusion is accurately reconstructed and the reconstruction of the density is well achieved., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The redundancy of genomic resources, including transcript and molecular markers, and their uncertain position in the genome have dramatically hindered the study of traits in ramie, an important natural fiber crop., Results: We obtained a high-quality transcriptome consisting of 30,591 non-redundant transcripts using single-molecule long-read sequencing and proposed it as a universal ramie transcriptome. Additionally, 55,882 single nucleotide polymorphisms (SNPs) were identified and a high-density genetic map was developed. Based on this genetic map, 181.7 Mb ramie genome sequences were assembled into 14 chromosomes. For the convenient use of these resources, 29,286 (~ 95.7%) of the transcripts and all 55,882 SNPs, along with 1827 previously reported sequence repeat markers (SSRs), were mapped into the ramie genome, and 22,343 (~ 73.0%) transcripts, 50,154 (~ 89.7%) SNPs, and 1466 (~ 80.3%) SSRs were assigned to a specific location in the corresponding chromosome., Conclusion: This is the first study to characterize the ramie transcriptome by long-read sequencing, and the substantial number of transcripts of significant length obtained will accelerate our understanding of ramie growth and development. This integration of genome sequences, expressed transcripts, and genetic markers will provide an extremely useful resource for genetic, molecular, and breeding studies of ramie.

In this study, we investigated the anticancer potentials of Rhein, an anthraquinone derivative of most commonly used Chinese rhubarb on the rat F98 glioma cells. The experimental studies revealed that Rhein induced cell cycle arrest, caspase mediated apoptosis. It results in the formation of intracellular acidic vesicles in cytoplasm, leading to autophagy. Differentiation of viable cells towards elongation of matured astrocytes was proved by monitoring dramatic changes in morphological characteristics as well as identified from the elevation of glial fibrillary acidic protein (GFAP) expression. Rhein treatment did not alter the phosphorylated MAPKs activation including p-38, JNK and NF-κB, transcription unit whereas rhein significantly inhibited ERK1/2 activation in F98 glioma cells. PD98059, a specific inhibitor for ERK activation imitates rhein effects on morphology and expressions of GFAP but did not help to induce any apoptosis or autophagy. Collective data exhibited that potentials of rhein in anti-cancer property in ERK-independent apoptosis and autophagy in association with downregulated ERK-dependent differentiation process of glioma cell lines., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Huperzine A is a potent, reversible, and blood-brain barrier permeable acetylcholinesterase inhibitor. The aim of this study was to compare the pharmacokinetics, tolerability, and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting, healthy Chinese male population. This was a randomized, single-dose, 3-period, 6-sequence crossover study. The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry. Tolerability was assessed based on subject interview, vital sign monitoring, physical examination, and routine blood and urine tests. The mean (SD) pharmacokinetic parameters of the reference drug were C max , 1.550 (0.528) ng/mL; t 1/2 , 12.092 (1.898) h; AUC 0-72h , 17.550 (3.794) ng·h/mL. Those of the test formulation A and test formulation B were C max , 1.412 (0.467), 1.521 (0.608) ng/mL; t 1/2 , 12.073 (2.068), 12.271 (1.678) h; AUC 0-72h , 15.286 (3.434) ng·h/mL, 15.673 (3.586) ng·h/mL. The 90% confidence intervals for the AUC 0-72h and C max were between 0.80 and 1.25. No adverse events were reported by the subjects or found with results of clinical laboratory test. The test and reference products met the regulatory criteria for bioequivalence in these fasting, healthy Chinese male volunteers. All three formulations appeared to be well tolerated.

Hepatic adverse reaction associated with Polygoni Multiflori Radix (PMR) has been frequently reported in recent years. Highly-enriched anthraquinones (AQs) in PMR, such as emodin, chrysophanol and physcion, have been found to be hepatotoxic. In the present study, sandwich-cultured rat hepatocytes (SCRHs) were employed to investigate the effect of individual and combined AQs on the disposition of endogenous bile acids (BAs) and exogenous probe substrates including deuterium-labeled taurocholate (d 5 -TCA), glycochenodeoxycholic acid (d 4 -GCDCA) and 5 (and 6)-carboxy-2',7'-dichlorofluorescein (CDF). Emodin and chrysophanol significantly inhibited bile salt export pump and multidrug resistance-associated protein 2 (Mrp2), respectively, as evidenced by decreased biliary excretion index (BEI) of d 5 -TCA and CDF. Moreover, basolateral efflux transporters were inhibited by all individual and combined AQs. As a result, cellular accumulation of total and specific endogenous BAs were significantly elevated by individual AQs, alone or combined. In addition, down-regulation of Mrps in both gene and protein levels by AQs served as another critical contributing factor for BA accumulation in SCRHs. To be noted, subsequent adaptive gene regulation, including reduced Ntcp expression, upregulated Bsep levels, and downregulated Cyp8b1, alleviated, to a certain extent, but not prevented from toxic BA accumulation. In summary, all three AQs of interest are likely to alter BA disposition through direct inhibition of BA transporters as well as regulated expression of BA transporters and enzymes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To investigate the association of non-bacterial respiratory pathogens with asthmatic diseases in children, and the clinical significance of total serum IgE levels and peripheral eosinophil count in infection with non-bacterial respiratory pathogens., Methods: Indirect immunofluorescence assay was used to detect IgM antibodies against nine types of non-bacterial respiratory pathogens in the sera of 490 children with asthmatic diseases between September 2010 and September 2011. Pathogens were analyzed and total serum IgE levels and peripheral eosinophil count were measured in IgM-positive cases., Results: Of the 490 children with asthmatic diseases, 47.6% (233 cases) were positive with IgM antibodies against non-bacterial respiratory pathogens, the most common being Mycoplasma pneumoniae (MP) (25.3%), followed by adenovirus (ADV) (8.9%) and influenza B virus (Flu B) (8.8%). Thirty-six cases suffered from co-infection of two or more non-bacterial pathogens, mainly comprising MP and other pathogens (94%). There were significant differences in the total detection rate of IgM antibodies among all age groups (0-30 days: 50.0%; 1-6 months: 67.3%; 0.5-1 year: 33.1%; 1-3 years: 57.3%; 3-8.9 years: 61.7%). The positive rate of IgM antibodies against respiratory pathogens was highest in children with bronchial asthma, followed by children with asthmatic bronchitis, and it was lowest in children with bronchiolitis. IgM-positive children had significantly decreased blood eosinophils and significantly increased total serum IgE levels., Conclusions: The main non-bacterial respiratory pathogens include MP, ADV and Flu B in children with asthmatic diseases, and co-infection of MP and other non-bacterial pathogens is common. Infants aged 1 to 6 months have a higher infection rate than other age groups. Monitoring the changes in total serum IgE levels and peripheral eosinophil count has great significance for the clinical diagnosis and treatment of asthmatic diseases in children.

Medulloblastoma is the most common malignant tumor of the central nervous system in children. The insulin-like growth factor-I receptor (IGF-IR) is an important growth factor for medulloblastoma. The novel IGF-I receptor (IGF-IR) kinase inhibitor NVP-ADW742 has in vitro activity against tumors. Daoy cells were treated with NVP-ADW742 combined with temozolomide, which is commonly used in the chemotherapy of medulloblastoma. The effects on proliferation were assayed by CCK-8 assay. Cell cycle status and apoptosis were assayed by FACS analysis. The IGF-IR signaling pathway was analyzed by RT2 Profiler™ PCR arrays and Western blotting. NVP-ADW742 inhibited IGF-IR-mediated proliferation with an IC50 of 11.12 µmol/l. The PCR array data suggested that 14 genes were down-regulated at the mRNA level after NVP-ADW742 treatment. Western blot analysis suggested that NVP-ADW742 induced early suppression of Akt, P38 and GSK-3β phosphorylation, as well as a decrease in the intracellular levels of PI3K, Akt, P38, GSK-3β and Bcl-2. Combined with NVP-ADW742 (2 µmol/l), IC50 of Daoy to temozolomide was decreased from 452.12 to 256.81 µmol/l. Cell apoptosis was enhanced from 16.18±2.47% to 23.20 ± 2.80%. G phase arrest was also found in both the temozolomide alone group and the temozolomide combined with NVP-ADW742 group. NVP-ADW742 inhibited the activation of PI3K, Akt, P38 and GSK-3β caused by temozolomide. NVP-ADW742 enhanced the chemosensitivity of Daoy to temozolomide in vitro, as a potent anti-tumor agent highly selective against IGF-IR.

Objective: To investigate the application of proton magnetic resonance spectroscopy (1HMRS) and computerized tomography (CT) in evaluating nonalcoholic fatty liver disease (NAFLD)., Methods: Twenty-two NAFLD patients were selected, according to the Chinese Medical Association standard, and compared with 20 healthy persons (as the control group). Their body mass index (BMI), waist to hip ratio (WHR), and blood pressure (BP) were examined. The serum ALT, the concentration of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and uric acid (UA) were tested simultaneously. The severity of hepatosteatosis was evaluated by 1HMRS and CT scans of their livers. The intrahepatic content of lipid (IHCL) and CT liver and spleen ratios were measured., Results: The BMI, WHR, serum ALT, FBG, TG, and UA were all elevated significantly in the NAFLD group and were (28.4+/-2.4) kg/m2, 0.91+/-0.04, (71.5+/-24.8) U/L, (5.67+/-0.61) mmol/L, (2.48+/-1.46) mmol/L, (420.7+/-57.5)micromol/L, respectively, P less than 0.01 or 0.05. Meanwhile, in the NAFLD group, the IHCL calculated by 1HMRS were increased and CT value ratios were decreased significantly compared with those of the control group (27.49%+/-12.27% vs 1.34%+/-0.79%, P less than 0.01). However, there was no correlation between the clinical features and the IHCL and between the clinical features and CT value ratios, but a negative correlation existed in the CT value ratio and IHCL., Conclusions: The intrahepatic content of lipids can be measured precisely by 1HMRS, and 1HMRS is better than CT in quantitative evaluations of NAFLD.