Biosynthesis of the benzylpyrrolidine precursor in anisomycin by a unique ThDP-dependent enzyme.

Anisomycin (compound 1), a multifunctional pyrrolidine antibiotic, primarily inhibits protein biosynthesis by binding to the ribosome. Upon binding to the ribosome, the para-phenol moiety of anisomycin inserts completely into the hydrophobic crevice of the A-site and blocks the access of the incoming aminoacyl-tRNAs, disrupting peptide bond formation. Hence, the para-methoxyphenyl group serves as a starting point for developing novel anisomycin analogs with potent antifungal and insecticidal properties. However, the activation and condensation mechanism of phenylpyruvic acid has not yet been elucidated. In this study, genetic manipulations of aniP and its homologue siAniP confirmed their indispensable role in 1 biosynthesis. Bioinformatics analysis suggested that AniP and siAniP function as transketolase. siAniP was found to catalyzed condensation between 4-hydroxyphenylpyruvic acid (3) and glyceraldehyde (GA), initiating pyrrolidine synthesis. siAniP was specific for aromatic keto acids and tolerant of aliphatic and aromatic aldehydes, and was able to catalyze the asymmetric intermolecular condensation of two keto acids, leading to the formation of 24 α-hydroxy ketone. To the best of our knowledge, siAniP is the first TK that catalyzes the transfer of a C2 ketol and symmetrical intermolecular coupling using aromatic keto acids as donor substrates. Structural analysis, docking model construction, and site-directed mutagenesis identified that I220, H275, R322 and W391 were crucial for substrate binding. Moreover, sequence similarity network (SSN)-based genome neighborhood network (GNN) analyses of AniP suggested the widespread occurrence of the AniP-like-mediated reaction in the biosynthesis of 1 and its analogs, particularly in the assembly of benzylpyrrolidine. These findings not only expand the repertoire of TKs but also provide a potent biocatalyst that could be used for the structural innovation of 1 and its derivatives.

Biocontrol and growth promotion potential of Bacillus velezensis NT35 on Panax ginseng based on the multifunctional effect.

The Bacillus velezensis strain NT35, which has strong biocontrol ability, was isolated from the rhizosphere soil of Panax ginseng. The antifungal effects of the NT35 strain against the mycelium and spore growth of Ilyonectria robusta, which causes ginseng rusty root rot, were determined. The inhibitory rate of I. robusta mycelial growth was 94.12% when the concentration of the NT35 strain was 107 CFU·mL-1, and the inhibitory rates of I. robusta sporulation and spore germination reached 100 and 90.31%, respectively, when the concentration of the NT35 strain was 104 and 108 CFU·mL-1, respectively. Strain NT35 had good prevention effects against ginseng rust rot indoors and in the field with the control effect 51.99%, which was similar to that of commercial chemical and biocontrol agents. The labeled strain NT35-Rif160-Stre400 was obtained and colonized ginseng roots, leaves, stems and rhizosphere soil after 90 days. Bacillus velezensis NT35 can induce a significant increase in the expression of five defensive enzyme-encoding genes and ginsenoside biosynthesis-related genes in ginseng. In the rhizosphere soil, the four soil enzymes and the microbial community improved during different periods of ginseng growth in response to the biocontrol strain NT35. The NT35 strain can recruit several beneficial bacteria, such as Luteimonas, Nocardioides, Sphingomonas, and Gemmatimonas, from the rhizosphere soil and reduce the relative abundance of Ilyonectria, Fusarium, Neonectria and Dactylonectria, which cause root rot and rusty root rot in ginseng plants. The disease indices were significantly negatively correlated with the abundances of Sphingomonas and Trichoderma. Additionally, Sphingomonadales, Sphingomonadaceae and actinomycetes were significantly enriched under the NT35 treatment according to LEfSe analysis. These results lay the foundation for the development of a biological agent based on strain NT35.

Distribution characteristics of antinuclear antibodies in Guillain-Barré syndrome and its relationship with disease severity.

BACKGROUND: Guillain-Barré syndrome (GBS), an acquired immune-mediated autoimmune disorder affecting the peripheral nervous system (PNS), is associated with autoimmunity. The presence of autoantibodies in the blood is an important feature of autoimmune diseases. Herein, we explored the distribution characteristics of the antinuclear antibodies (ANAs) in GBS and the correlation between ANAs and disease severity. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 170 GBS patients. According to ANAs, GBS patients were divided into ANAs positive and negative groups. The clinical characteristics of these two groups were compared. The distribution difference was also compared between male and female GBS patients. In addition, all enrolled patients were divided into more severe group and milder group according to whether the Hughes score at nadir ≥ 3 or not. Gender, age, and ANAs were compared between the two groups. RESULTS: In this study, the positive rate of ANAs was 27.1 % in 170 GBS patients, among which anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 made up the largest proportion. In the ANAs positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, and higher level of CSF IgG than the ANAs negative group. Compared to the ANAs negative group, Medical Research Council (MRC) scores on admission and at nadir were lower, and Hughes functional Grading Scale (HFGS) scores on admission and at nadir were higher in GBS patients with ANAs positive group. Erasmus GBS Respiratory Insufficiency Score (EGRIS) in ANAs positive GBS patients group was significantly higher than ANAs negative group. Gender had no effects on the distribution of ANAs in GBS patients. Moreover, we found that the anti-SSA-60 antibodies and age were positively correlated with GBS severity. In addition, in the anti-SSA-60 antibody positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, higher HFGS scores on admission/at nadir, and lower MRC scores at nadir compared with the anti-SSA-60 antibody negative group. CONCLUSION: Anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 were the most common ANAs in GBS patients. Anti-SSA-60 antibodies and age positively correlated with GBS severity. Positive anti-SSA-60 antibodies and age were independent predictors of GBS patient severity.

Accurate 3D LiDAR SLAM System Based on Hash Multi-Scale Map and Bidirectional Matching Algorithm.

Simultaneous localization and mapping (SLAM) is a hot research area that is widely required in many robotics applications. In SLAM technology, it is essential to explore an accurate and efficient map model to represent the environment and develop the corresponding data association methods needed to achieve reliable matching from measurements to maps. These two key elements impact the working stability of the SLAM system, especially in complex scenarios. However, previous literature has not fully addressed the problems of efficient mapping and accurate data association. In this article, we propose a novel hash multi-scale (H-MS) map to ensure query efficiency with accurate modeling. In the proposed map, the inserted map point will simultaneously participate in modeling voxels of different scales in a voxel group, enabling the map to represent objects of different scales in the environment effectively. Meanwhile, the root node of the voxel group is saved to a hash table for efficient access. Secondly, considering the one-to-many (1 ×103 order of magnitude) high computational data association problem caused by maintaining multi-scale voxel landmarks simultaneously in the H-MS map, we further propose a bidirectional matching algorithm (MSBM). This algorithm utilizes forward-reverse-forward projection to balance the efficiency and accuracy problem. The proposed H-MS map and MSBM algorithm are integrated into a completed LiDAR SLAM (HMS-SLAM) system. Finally, we validated the proposed map model, matching algorithm, and integrated system on the public KITTI dataset. The experimental results show that, compared with the ikd tree map, the H-MS map model has higher insertion and deletion efficiency, both having O(1) time complexity. The computational efficiency and accuracy of the MSBM algorithm are better than that of the small-scale priority matching algorithm, and the computing speed of the MSBM achieves 49 ms/time under a single CPU thread. In addition, the HMS-SLAM system built in this article has also reached excellent performance in terms of mapping accuracy and memory usage.

Transcutaneous Electrical Acupoint Stimulation Combined with Moderate Sedation of Remimazolam Tosilate in Gastrointestinal Endoscopy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. METHODS: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. RESULTS: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. CONCLUSIONS: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. TRIAL REGISTRATION: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

Posterior mediastinal leiomyosarcoma: Case report and literature review.

BACKGROUND: Posterior mediastinal leiomyosarcoma is an extremely rare malignant mesenchymal tumor with no special clinical symptoms, which is easily confused with some common tumors in the posterior mediastinum, affecting the accuracy of the first diagnosis by clinicians and delaying the treatment of patients. CASE SUMMARY: We report a 59-year-old woman with a space-occupying lesion in the posterior mediastinum. The patient was mistakenly diagnosed with lumbar muscle or vertebral body lesions due to chest and back pain and underwent conservative treatment, but her symptoms did not improve significantly and she gradually developed pain in both lower limbs. Chest computed tomography (CT) scan indicated the left lower lung paraspinal space and underwent standard single-aperture video-assisted thoracoscopic surgery (VATS), which was pathologically confirmed as posterior mediastinal leiomyosarcoma. CONCLUSION: Complete surgical resection of posterior mediastinal leiomyosarcoma can achieve good clinical results.

Multicomponent nickel-molybdenum-tungsten-based nanorods for stable and efficient alkaline seawater splitting.

The electrolysis of seawater for hydrogen production holds promise as a sustainable technology for energy generation. Developing water-splitting catalysts with low overpotential and stable operation in seawater is essential. In this study, we employed a hydrothermal method to synthesize NiMoWOX microrods (NiMoWOX@NF). Subsequently, an annealing process yielded a composite N-doped carbon-coated Ni3N/MoO2/WO2 nanorods (NC@Ni3N/MoO2/WO2@NF), preserving the ultrahigh-specific surface area of the original structure. A two-electrode electrolytic cell was assembled using NC@Ni3N/MoO2/WO2@NF as the cathode and NiMoWOX@NF as the anode, demonstrating exceptional performance in seawater splitting. The cell operated at a voltage of 1.51 V with a current density of 100 mA·cm-2 in an alkaline seawater solution. Furthermore, the NC@Ni3N/MoO2/WO2@NF || NiMoWOX@NF electrolytic cell exhibited remarkable stability, running continuously for over 120 h at a current of 1100 mA·cm-2 without any observable delay. These experimental results are corroborated by density functional theory calculations. The NC@Ni3N/MoO2/WO2@NF || NiMoWOX@NF electrolyzer emerges as a promising option for industrial-scale hydrogen production through seawater electrolysis.

STGIC: A graph and image convolution-based method for spatial transcriptomic clustering.

Spatial transcriptomic (ST) clustering employs spatial and transcription information to group spots spatially coherent and transcriptionally similar together into the same spatial domain. Graph convolution network (GCN) and graph attention network (GAT), fed with spatial coordinates derived adjacency and transcription profile derived feature matrix are often used to solve the problem. Our proposed method STGIC (spatial transcriptomic clustering with graph and image convolution) is designed for techniques with regular lattices on chips. It utilizes an adaptive graph convolution (AGC) to get high quality pseudo-labels and then resorts to dilated convolution framework (DCF) for virtual image converted from gene expression information and spatial coordinates of spots. The dilation rates and kernel sizes are set appropriately and updating of weight values in the kernels is made to be subject to the spatial distance from the position of corresponding elements to kernel centers so that feature extraction of each spot is better guided by spatial distance to neighbor spots. Self-supervision realized by Kullback-Leibler (KL) divergence, spatial continuity loss and cross entropy calculated among spots with high confidence pseudo-labels make up the training objective of DCF. STGIC attains state-of-the-art (SOTA) clustering performance on the benchmark dataset of 10x Visium human dorsolateral prefrontal cortex (DLPFC). Besides, it's capable of depicting fine structures of other tissues from other species as well as guiding the identification of marker genes. Also, STGIC is expandable to Stereo-seq data with high spatial resolution.

Tumor blood vessel in 3D reconstruction CT imaging as an risk indicator for growth of pulmonary nodule with ground-glass opacity.

OBJECTIVE: Despite the vital role of blood perfusion in tumor progression, in patients with persistent pulmonary nodule with ground-glass opacity (GGO) is still unclear. This study aims to investigate the relationship between tumor blood vessel and the growth of persistent malignant pulmonary nodules with ground-glass opacity (GGO). METHODS: We collected 116 cases with persistent malignant pulmonary nodules, including 62 patients as stable versus 54 patients in the growth group, from 2017 to 2021. Three statistical methods of logistic regression model, Kaplan-Meier analysis regression analysis were used to explore the potential risk factors for growth of malignant pulmonary nodules with GGO. RESULTS: Multivariate variables logistic regression analysis and Kaplan-Meier analysis identified that tumor blood vessel diameter (p = 0.013) was an significant risk factor in the growth of nodules and Cut-off value of tumor blood vessel diameter was 0.9 mm with its specificity 82.3% and sensitivity 66.7%.While in subgroup analysis, for the GGO CTR < 0.5[C(the maximum diameter of consolidation in tumor)/T(the maximum diameter of the whole tumor including GGO) ratio], tumor blood vessel diameter (p = 0.027) was important during the growing processes of nodules. CONCLUSIONS: The tumor blood vessel diameter of GGO lesion was closely associated with the growth of malignant pulmonary nodules. The results of this study would provide evidence for effective follow-up strategies for pulmonary nodule screening.

Predicting pleural invasion of invasive lung adenocarcinoma in the adjacent pleura by imaging histology.

The aim of the present study was to develop a non-invasive method based on histological imaging and clinical features for predicting the preoperative status of visceral pleural invasion (VPI) in patients with lung adenocarcinoma (LUAD) located near the pleura. VPI is associated with a worse prognosis of LUAD; therefore, early and accurate detection is critical for effective treatment planning. A total of 112 patients with preoperative computed tomography presentation of adjacent pleura and postoperative pathological findings confirmed as invasive LUAD were retrospectively enrolled. Clinical and histological imaging features were combined to develop a preoperative VPI prediction model and validate the model's efficacy. Finally, a nomogram for predicting LUAD was established and validated using a logistic regression algorithm. Both the clinical signature and radiomics signature (Rad signature) exhibited a perfect fit in the training cohort. The clinical signature was overfitted in the testing cohort, whereas the Rad signature showed a good fit. To combine clinical and radiomics signatures for optimal performance, a nomogram was created using the logistic regression algorithm. The results indicated that this approach had the highest predictive performance, with an area under the curve of 0.957 for the clinical signature and 0.900 for the Rad signature. In conclusion, histological imaging and clinical features can be combined in columnar maps to predict the preoperative VPI status of patients with adjacent pleural infiltrative lung carcinoma.

Neoadjuvant therapy for HER2-positive acantholytic squamous cell breast carcinoma: a case report.

HER2-positive acantholytic squamous cell carcinoma (ASCC) of the breast is exceptionally rare, and its clinicopathologic features are poorly understood. The impact of neoadjuvant therapy on HER2-positive breast ASCC is unclear. Here we report on a 58-year-old woman who was diagnosed with HER2-positive ASCC of the right breast, who underwent neoadjuvant treatment with albumin-paclitaxel, carboplatin, and trastuzumab, and surgery. Neoadjuvant therapy was effective, with no recurrence or metastasis after 1.5 years of postoperative follow-up.

GsNAC2 gene enhances saline-alkali stress tolerance by promoting plant growth and regulating glutathione metabolism in Sorghum bicolor.

The quality and yields of Sorghum bicolo r plants are seriously affected by saline-alkali conditions. NAC (NAM, ATAF, and CUC) transcription factors are plant specific and have various functions in plant development and response to various stresses. To investigate how GsNAC2 functions in sorghum responses to saline-alkali treatment, the characteristics of GsNAC2 were analysed by bioinformatics methods, and NaHCO3 :Na2 CO3 (5:1, 75mM, pH 9.63) saline-alkali stress solution was applied when sorghum plants were 2weeks old. The research results show that GsNAC2 belongs to the NAC gene family. GsNAC2 was significantly induced by saline-alkali treatment and strongly expressed in sorghum leaves. GsNAC2 -overexpressing sorghum plants had increased plant height, dry weight, moisture content, root activity, leaf length, chlorophyll content, stomatal conductance, relative root activity, relative chlorophyll content, relative stomatal conductance, and relative transpiration rate after saline-alkali treatment. Lower H2 O2 and O2 - levels, relative permeability of the plasma membrane, and malondialdehyde (MDA) content were found in GsNAC2 -overexpressing sorghum. In transcriptome analysis, clusters of orthologous groups (COG) analysis showed that a high proportion of differentially-expressed genes (DEGs) participated in defence mechanisms at each processing time, and 18 DEGs related to synthetic glutathione were obtained. Gene expression analysis revealed that key genes in glutathione biosynthesis pathways were upregulated. GR and GSH-Px activities were increased, and GSH accumulated more with the overexpression of GsNAC2 after saline-alkali treatment. Furthermore, these results suggest that GsNAC2 acts as a potentially important regulator in response to saline-alkali stress and may be used in molecular breeding to improve crop yields under adverse environmental conditions.

Prognostic significance of Memorial Sloan-Kettering prognostic score in small-cell lung cancer patients.

Aim: To assess the potential factors with predictive value for survival in small-cell lung cancer (SCLC) patients and to develop a nomogram prediction model. Patients & methods: We retrospectively screened and analyzed patients with pathologically confirmed SCLC from April 2015 to December 2021. Results: A total of 167 patients with SCLC were included. According to the Memorial Sloan-Kettering prognostic score (MPS), patients were divided into three groups: group 0 (n = 65), group 1 (n = 69) and group 2 (n = 33). The multivariate analysis showed that MPS was an independent prognostic factor for progression-free and overall survival in SCLC patients (p < 0.05). The nomogram showed that MPS was the most influential factor for overall survival. Conclusion: MPS is an independent prognostic factor for overall and progression-free survival in SCLC patients and performed better than other indicators used in this study.

Sustainable safe and environmentally friendly process to recovery valuable materials from hazardous waste InP.

With the rapid expansion of the market scale for indium phosphide (InP) semiconductors in high-tech industries such as optoelectronics and solar energy, the generation of hazardous waste InP has also increased dramatically, and the task of recycling waste InP is urgent. However, InP as a representative phosphide semiconductor is prone to produce highly toxic substances such as yellow phosphorus and PH3 in the recycling process, which discourages most companies from using it. In this study, a safe and efficient method of "vacuum decomposition-directional condensation (VD-DC)" is proposed to recover valuable materials from waste InP. In this method, briquetting pretreatment is used to improve thermal conductivity. At a decomposition temperature of 1123 K, system pressure of 30 Pa, and holding time of 3.5 h, indium with a purity of 99.43 wt% is obtained, and the direct yield reaches 98.54%. Non-toxic and stable red phosphorus with a purity of 98.14 wt% is recovered by converting the condensed yellow phosphorus at 573 K. Vacuum technology significantly reduces the decomposition temperature of InP and avoids the emission of waste water and waste gas, thus operating in an environmentally friendly manner.

Comparison of surface passivation modification of two mordenite zeolites and their application on the isomerisation of o-ethyltoluene.

During the isomerisation of o-ethyltoluene (O-ET) to produce m-ethyltoluene (M-ET) and p-ethyltoluene (P-ET), it is crucial to improve the isomerisation selectivity and reduce side reactions, such as disproportionation, alkyl transfer, and splitting. In this study, in order to improve the selectivities toward M-ET and P-ET during O-ET isomerisation, both the commercial micropore mordenite (HM) and the prepared micro-mesoporous mordenite (HM-M) were treated through chemical liquid deposition using tetraethyl orthosilicate (TEOS) and 3,5-dimethylphenylmagnesium bromide (DPB), respectively. Thereafter, their structure, porosity, and acidity were characterized via X-ray diffraction, transmission electron microscopy, inductively coupled plasma, N2 sorption, temperature-programmed desorption of ammonia, Fourier-transform infrared spectroscopy of pyridine and 2,6-di-tert-butylpyridine, and thermal analysis. The deposition mechanism of DPB was also discussed. The results showed that TEOS could shrink and block the micropores of mordenite. By contrast, DPB passivated the external surface acidity and did not affect the micropore structure. Moreover, HM modified using DPB significantly shortened the self-coking process, improved the product selectivities for M-PT and P-ET as well as their stability, and prolonged the catalytic life. When the amount of magnesium oxide (MgO) deposited on the HM zeolite was 4%, the product selectivities toward M-ET and P-ET increased from 67.27% to 77.54%, and the yields of M-ET and P-ET increased from 47.57% to 52.98%. However, the performance of the catalyst was not significantly enhanced on the HM-M, owing to the passivation of acidic sites in the mesopores by the TEOS and DPB.

Genome-wide identification and characterization of the C2 domain family in Sorghum bicolor (L.) and expression profiles in response to saline-alkali stress.

The C2 domain family proteins in plants has been recently shown to be involved in the response to abiotic stress such as salt and drought stress. However, less information on C2 domain family members has been reported in Sorghum bicolor (L.), which is a tolerant cereal crop. To elaborate the mechanism of C2 domain family members in response to abiotic stress, bioinformatic methods were used to analyze this family. The results indicated that 69 C2 domain genes belonging to 5 different groups were first identified within the sorghum genome, and each group possessed various gene structures and conserved functional domains. Second, those C2 family genes were localized on 10 chromosomes 3 tandem repeat genes and 1 pair of repeat gene fragments were detected. The family members further presented a variety of stress responsive cis-elements. Third, in addition to being the major integral component of the membrane, sorghum C2 domain family proteins mainly played roles in response to abiotic and biotic stress with their organic transport and catalytic activity by specific location in the cell on the basis of gene ontology analysis. C2 family genes were differentially expressed in root, shoot or leaf, and shown different expression profiling after saline-alkali stress, which indicated that C2 family members played an important role in response to saline-alkali stress based on the transcription profiles of RNA-seq data and expression analysis by quantitative real-time polymerase chain reaction. Besides, most C2 family members were mainly located in cytoplasmi and nucleus. Weighted gene co-expression network analysis revealed three modules (turquoise, dark magenta and pink) that were associated with stress resistance, respectively. Therefore, the present research provides comprehensive information for further analysis of the molecular function of C2 domain family genes in sorghum. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01222-3.

Correction to: Genome-wide identifcation and characterization of the C2 domain family in Sorghum bicolor (L.) and expression profles in response to saline-alkali stress.

[This corrects the article DOI: 10.1007/s12298-022-01222-3.].