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BackgroundChina is a country with a high burden of tuberculosis (TB). TB outbreaks are frequent in schools. Thus, understanding the transmission patterns is crucial for controlling TB.MethodIn this genomic epidemiological study, the conventional epidemiological survey data combined with whole-genome sequencing was used to assess the genotypic distribution and transmission characteristics of Mycobacterium tuberculosis strains isolated from patients with TB attending schools during 2015 to 2019 in Guangzhou, China.ResultThe TB incidence was mainly concentrated in regular secondary schools and technical and vocational schools. The incidence of drug resistance among the students was 16.30% (22/135). The phylogenetic tree showed that 79.26% (107/135) and 20.74% (28/135) of the strains belonged to lineage 2 (Beijing genotype) and lineage 4 (Euro-American genotype), respectively. Among the 135 isolates, five clusters with genomic distance within 12 single nucleotide polymorphisms were identified; these clusters included 10 strains, accounting for an overall clustering rate of 7.4% (10/135), which showed a much lower transmission index. The distance between the home or school address and the interval time of symptom onset or diagnosis indicated that campus dissemination and community dissemination may be existed both, and community dissemination is the main.Conclusion and recommendationTB cases in Guangzhou schools were mainly disseminated and predominantly originated from community transmission. Accordingly, surveillance needs to be strengthened to stop the spread of TB in schools.

In this study, changes in volatile compounds co-fermented by different Pichia kluyveri with Saccharomyces cerevisiae were analyzed using GC-IMS and compared with S. cerevisiae fermentation, to investigate the production of aroma in mulberry wine during the fermentation process. A total of 61 compounds were accurately identified, including 21 esters, 10 alcohols, 8 aldehydes, 6 ketones, and 19 other volatiles. Compared with the single strain fermentation (S. cerevisiae), the content of 2-methylpropyl acetate, allyl Isothiocyanate, ethyl crotonate, isobutyl propanoate, and butyl 2-methylbutanoate, co-fermentation groups (S. cerevisiae with different P. kluyveri) showed a significant decrease. Alcohols, aldehydes, ketones, and organic acid were lower in both the F(S-P1) and F(S-P2) groups than in the F(S) group throughout fermentation. The 2-methylpentanoic acid only was contained in the F(S) group. The co-fermentation with different P. kluyveri could also be well distinguished. The content of Benzaldehyde and 4-methylphenol in the F(S-P1) group was significantly lower than that in the F(S-P2) group. The PCA results revealed effective differentiation of mulberry wine fermented by different fermentation strains from GC-IMS. The result showed that P. kluyveri could establish a new flavor system for mulberry wine, which plays a crucial role in enhancing the flavor of fruit wine.

Metastasis, a major cause of cancer-related mortality worldwide, frequently occurs early in the diagnosis of lung adenocarcinoma (LUAD). However, the precise molecular mechanisms governing the aggressive metastatic behavior of LUAD remain incompletely understood. In this study, we present compelling evidence indicating that the long noncoding RNA linc01703 is significantly downregulated in metastatic lung cancer cells. Intriguingly, in vivo experiments revealed that Linc01703 exerted a profound inhibitory effect on lung cancer metastasis without discernible impact on the in vitro proliferation or invasion capacities of LUAD cells. Mechanistically, Linc01703 enhanced the interaction between Rab27a, SYTL1, and CD81, consequently promoting the secretion of CD81+ exosomes. These exosomes, in turn, suppressed the infiltration of immune cells within the tumor microenvironment, thereby impeding LUAD metastasis. Importantly, our analysis of lung cancer tissues revealed a correlation between reduced CD81 expression and an unfavorable patient prognosis. Collectively, our findings suggest that Linc01703 functions as a metastasis suppressor by facilitating the secretion of CD81+ exosomes through the formation of the Rab27a/SYTL1/CD81 complex.

Voltage-induced heating defect is a type of defect that may occur in transformation substation equipment. Although this type of defect is less common compared to current-induced heating defects, it is crucial to identify it due to its association with severe insulation degradation problems that require prompt intervention. However, the temperature variations caused by these defects may be relatively subtle, making it challenging to distinguish them in thermal images. In this work, considering the characteristics of voltage-induced heating defects and the scarcity of defect data, we propose a two-stage method for defect detection. In the first stage, we employ oriented R-CNN to detect oriented parts of the equipment, accurately localizing the centerline of each part. In the second stage, we extract the temperature distribution along the centerline of specific parts and discretize them as features. Subsequently, we train one-class support vector machines based on the features extracted from normal images for defect diagnosis. Experimental results demonstrate that the proposed method is capable of accurately detecting defects while maintaining a low false positive rate.

Memristors are recognized as crucial devices for future nonvolatile memory and artificial intelligence. Due to their typical neuron-synapse-like metal–insulator–metal(MIM) sandwich structure, they are widely used to simulate biological synapses and have great potential in advancing biological synapse simulation. However, the high switch voltage and inferior stability of the memristor restrict the broader application to the emulation of the biological synapse. In this study, we report a vertically structured memristor based on few-layer MoS2. The device shows a lower switching voltage below 0.6 V, with a high ON/OFF current ratio of 104, good stability of more than 180 cycles, and a long retention time exceeding 3 × 103 s. In addition, the device has successfully simulated various biological synaptic functions, including potential/depression propagation, paired-pulse facilitation (PPF), and long-term potentiation/long-term depression (LTP/LTD) modulation. These results have significant implications for the design of a two-dimensional transition-metal dichalcogenides composite material memristor that aim to mimic biological synapses, representing promising avenues for the development of advanced neuromorphic computing systems.

Extracting river channels from remote sensing images is crucial for locating river water bodies and efficiently managing water resources, especially in cold and arid regions. The dynamic nature of river channels in these regions during the flood season necessitates a method that can finely delineate the edges of perennially changing river channels and accurately capture information about variable fine river branches. To address this need, we propose a river channel extraction method designed specifically for detecting fine river branches in remote sensing images within cold and arid regions. The method introduces a novel river attention U-shaped network structure (RAU-Net++), leveraging the rich convolutional features of VGG16 for effective feature extraction. For optimal feature extraction along channel edges and fine river branches, we incorporate a CBAM attention module into the upper sampling area at the end of the encoder. Additionally, a residual attention feature fusion module (RAFF) is embedded at each short jump connection in the dense jump connection. Dense skip connections play a crucial role in extracting detailed texture features from river channel features with varying receptive fields obtained during the downsampling process. The integration of the RAFF module mitigates the loss of river information, optimizing the extraction of lost river detail feature information in the original dense jump connection. This tightens the combination between the detailed texture features of the river and the high-level semantic features. To enhance network performance and reduce pixel-level segmentation errors in medium-resolution remote sensing imagery, we employ a weighted loss function comprising cross-entropy (CE) loss, dice loss, focal loss, and Jaccard loss. The RAU-Net++ demonstrates impressive performance metrics, with precision, IOU, recall, and F1 scores reaching 99.78%, 99.39%, 99.71%, and 99.75%, respectively. Meanwhile, both ED and ED′ of the RAU-Net++ are optimal, with values of 1.411 and 0.003, respectively. Moreover, its effectiveness has been validated on NWPU-RESISC45 datasets. Experimental results conclusively demonstrate the superiority of the proposed network over existing mainstream methods.

For the residual film recycling machine work, after the recovery of residual film, cotton stalks, crushed soil, and other impurities are not easy to separate; it is challenging to realize the secondary use of the problem. A waste film and impurity wind selection device were designed to recognize waste film recycling and separate soil film rods. The overall structure and working principles of the machine are described. A three-dimensional computational fluid dynamics model of a film rod separation device was developed. The flow field within the film rod separation unit was analyzed by numerical simulation using 2023 R1 ANSYS Fluent software. Based on the differences of impurities such as residual film, soil, and cotton stalks in terms of density, suspension velocity, and their characteristics, the pressure distribution and velocity distribution of the internal flow field of soil, residual film, and cotton stalks at the site were investigated. The air inlet velocity, screen cylinder rotation, and main shaft rotation velocity were changed. Experiments were conducted to obtain wind selection parameters for suitable soil, residual film, and cotton stalk separators. Analysis of orthogonal experiments, polar variance of analysis, and analysis of variance yielded a better combination of working parameters: when the drum sieve velocity is 25 r/min, the spindle velocity is 35 r/min, and inlet wind velocity is 14 m/s, after the separation of residual film impurity rate of 8.9%. The results of the study can provide a theoretical basis for the development of film separation equipment.

Acetaldehyde is an important carbonyl compound commonly detected in wines. A high concentration of acetaldehyde can affect the flavor of wines and result in adverse effects on human health. Alcohol dehydrogenase I (ADH1) in Saccharomyces cerevisiae catalyzes the reduction reaction of acetaldehyde into ethanol in the presence of cofactors, showing the potential to reduce the content of acetaldehyde in wines. In this study, ADH1 was successfully expressed in Pichia pastoris GS115 based on codon optimization. Then, the expression level of ADH1 was enhanced by replacing its promoter with optimized promoters and increasing the copy number of the expression cassette, with ADH1 being purified using nickel column affinity chromatography. The enzymatic activity of purified ADH1 reached 605.44 ± 44.30 U/mg. The results of the effect of ADH1 on the content of acetaldehyde in wine revealed that the acetaldehyde content of wine samples was reduced from 168.05 ± 0.55 to 113.17 ± 6.08 mg/L with the addition of 5 mM NADH and the catalysis of ADH1, and from 135.53 ± 4.08 to 52.89 ± 2.20 mg/L through cofactor regeneration. Our study provides a novel approach to reducing the content of acetaldehyde in wines through enzymatic catalysis.

Endogenous reference genes play a crucial role in the qualitative and quantitative PCR detection of genetically modified crops. Currently, there are no systematic studies on the banana endogenous reference gene. In this study, the MaSPS1 gene was identified as a candidate gene through bioinformatics analysis. The conservation of this gene in different genotypes of banana was tested using PCR, and its specificity in various crops and fruits was also examined. Southern blot analysis showed that there is only one copy of MaSPS1 in banana. The limit of detection (LOD) test showed that the LOD of the conventional PCR method is approximately 20 copies. The real-time fluorescence quantitative PCR (qPCR) method also exhibited high specificity, with a LOD of approximately 10 copies. The standard curve of the qPCR method met the quantitative requirements, with a limit of quantification (LOQ) of 1.14 × 10−2 ng—about 20 copies. Also, the qPCR method demonstrated good repeatability and stability. Hence, the above results indicate that the detection method established in this study has strong specificity, a low detection limit, and good stability. It provides a reliable qualitative and quantitative detection system for banana.

Rolling bearings serve as the fundamental components of rotating machinery. Failure to detect damage early in these components can result in equipment shutdown, leading not only to economic losses but also to a threat to worker safety. Given the diverse range of rotating parts, it is crucial to promptly identify and accurately diagnose early bearing failures during the maintenance of large-scale machinery. To achieve quick and precise fault diagnosis, this study proposes a method based on dilated convolution, a Bidirectional Gated Recurrent Unit (BiGRU), and a multi-head self-attention mechanism. The key advantage lies in its ability to directly process raw 1D sampled data without requiring complex time–frequency domain conversion. To validate the model’s accuracy and stability, we conducted empirical studies using both the HUST bearing dataset proposed by Thuan, Nguyen et al. and the CWRU bearing dataset from Western Reserve University. The results demonstrate that our model achieves an impressive accuracy rate of 99.94%, along with an f1 value for the test set when dealing with multiple operating conditions for all five types of bearings in the HUST dataset. Moreover, when applied to the CWRU dataset, these two metrics even reached 99.95%. Furthermore, the proposed model achieves a significant prediction accuracy of more than 98.5% on two datasets containing different types of noise and different levels of white Gaussian noise, highlighting its great potential in practical applications of early bearing fault diagnosis.

Abstract Current chemical analysis approaches for contaminants have failed to reveal their biotoxicity. Moreover, conventional bioassays are time consuming and exhibit poor repeatability. In this study, we performed the acute toxicity detection of various contaminants (chromium (Cr), cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg), tin (Sn), nickel (Ni), and bisphenol A (BPA)) with four bioluminescent bacteria (Vibrio qinghaiensis Q67, V. fischeri, Photobacterium phosphoreum T3, and P. phosphoreum 502) using a rapid, flexible, and low‐cost bioassay. We found that the temperature affected the bacterial luminescence, and freeze‐dried cells exhibited sensitive toxic responses to contaminants. Indeed, the optimized protectants containing 12% (w/v) trehalose, 4% sucrose, and 2% sorbitol displayed better luminescence and toxic sensitivity. Furthermore, freeze‐dried powders of these strains were prepared and subjected to acute toxicity detection. The results showed that all contaminants exhibited acute toxicity toward Q67, but the other strains did not show obvious response to nickel and tin. The relative half‐maximal effective concentration (EC50) values of BPA, Cr, Cd, Pb, As, Hg, Ni, and Sn to Q67 were 0.674, 1.313, 11.137, 5.921, 4.674, 0.911, 5.941, and 54.077 mg/L, respectively. In addition, the EC50 values of contaminants toward different strains were suggested to be statistically significant. Freeze‐dried Q67 exhibited toxic responses to more contaminants than the other bioluminescent strains; therefore, Q67 was selected to be more suitable than the other strains for single and mixture toxicity detection tests. Compared with other strains, Q67 was more appropriate for the rapid screening of the mixture toxicity of contaminants in samples as a nonspecific screening sensor before the use of standard analysis approaches.

AIM: To evaluate the visual outcomes of Contoura Vision (CV) with automatic eye tracking system in eyes with myopia and myopic astigmatism. METHODS: This prospective study included 160 eyes (80 patients) with moderate myopia and irregular astigmatism between January and August 2018. Subjects were randomly divided into CV group (80 eyes) that underwent CV femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and a control group (80 eyes) that underwent wavefront-optimized FS-LASIK. Visual outcomes and astigmatic vector analysis were evaluated and compared between preoperatively and 3mo postoperatively. RESULTS: Basic details were similar in both groups (P>0.05). At 3mo postoperatively, uncorrected distance visual acuity was 20/16, 20/20, and 20/25 in 24, 76, and 80 eyes of patients in CV group, respectively. The CV group was better in predictability of astigmatism correction at 3mo postoperatively. In CV group, 64 eyes had deviation of astigmatic axis within 15° and 28 eyes had deviation of astigmatic axis within 5°, both were better than those in the control group. The number of eyes with residual astigmatism within 0.5 D were less in CV group (48 eyes) than the control group (40 eyes). Compared with the preoperative, C7 significantly reduced to 0.056±0.030 in CV group at 3mo after the procedure (P

Therapeutic options for patients with triple-negative breast cancer (TNBC) in later-line setting are limited. Here the authors report the results of a phase 2 clinical trial to evaluate efficacy and safety of the combination of camrelizumab (anti-PD1), apatinib (VEGFR2 inhibitor), and eribulin in patients with heavily pre-treated advanced TNBC.

Abstract Background Pichia pastoris (Komagataella phaffii) is a model organism widely used for the recombinant expression of eukaryotic proteins, and it can metabolize methanol as its sole carbon and energy source. Methanol is oxidized to formaldehyde by alcohol oxidase (AOX). In the dissimilation pathway, formaldehyde is oxidized to CO2 by formaldehyde dehydrogenase (FLD), S-hydroxymethyl glutathione hydrolase (FGH) and formate dehydrogenase (FDH). Results The transcriptome and metabolome of P. pastoris were determined under methanol cultivation when its dissimilation pathway cut off. Firstly, Δfld and Δfgh were significantly different compared to the wild type (GS115), with a 60.98% and 23.66% reduction in biomass, respectively. The differential metabolites between GS115 and Δfld were mainly enriched in ABC transporters, amino acid biosynthesis, and protein digestion and absorption. Secondly, comparative transcriptome between knockout and wild type strains showed that oxidative phosphorylation, glycolysis and the TCA cycle were downregulated, while alcohol metabolism, proteasomes, autophagy and peroxisomes were upregulated. Interestingly, the down-regulation of the oxidative phosphorylation pathway was positively correlated with the gene order of dissimilation pathway knockdown. In addition, there were significant differences in amino acid metabolism and glutathione redox cycling that raised our concerns about formaldehyde sorption in cells. Conclusions This is the first time that integrity of dissimilation pathway analysis based on transcriptomics and metabolomics was carried out in Pichia pastoris. The blockage of dissimilation pathway significantly down-regulates the level of oxidative phosphorylation and weakens the methanol assimilation pathway to the point where deficiencies in energy supply and carbon fixation result in inefficient biomass accumulation and genetic replication. In addition, transcriptional upregulation of the proteasome and autophagy may be a stress response to resolve formaldehyde-induced DNA–protein crosslinking.

Primary hepatic angiosarcoma (PHA), a rare soft tissue tumor, accounts for only 2% of all liver malignancies. Pathologically challenging, PHA is difficult to be distinguished from other malignancies with ultrasound, Computed Tomography (CT), or Magnetic Resonance Imaging (MRI). Due to late diagnosis and resistance against traditional chemotherapy and/or radiotherapy, only 3% of PHA patients can survive up to two years after diagnosis. To our best knowledge, this case report presents the first case of an advanced diffuse PHA with ruptured hemorrhage that has been effectively treated with TACE and Anlotinib plus Camrelizumab. So far, the patient has received 10 cycles of treatment and is faring well. Latest MRI results show that the tumor has shrunk by 56% and can be assessed as a partial response (PR). This case report includes our experience in treating such a advanced malignancy, and we hope that larger studies on advanced PHA can better quantify the potential benefit.

An autoimmune condition known as systemic lupus erythematosus (SLE) is characterized by B cell hyperresponsiveness and persistent generation of pathogenic autoantibodies that cause damage to various organs and tissues. The treatments available today are either ineffective or have adverse effects. The dysregulation of B cell activation is crucial for the emergence of SLE. MiR-7 explicitly targeted PTEN mRNA in B cells. Treatment with antagomiR-7 reduced B cell hyperresponsiveness and prevented the onset of lupus. As a result, inhibiting miR-7 may be used therapeutically to treat SLE. We developed a SA (sialic acid)-poly (D, L-lactide-co-glycolide) (SA-PLGA) nano delivery system to deliver antagomiR-7 into splenic B cells since the stability and targeted delivery of miRNA remain significant challenges in vivo. Results show that SA-PLGA nanoparticles (SA-PLGA@antagomiR-7) loaded with antagomiR-7 display good biocompatibility and shield antagomiR-7 from degradation, extending the miRNA’s duration in circulation in vivo. Additionally, in MRL/Ipr lupus mice, SA-PLGA@antagomiR-7 is successfully delivered to the splenic B cells and preferentially enriched in the diseased spleen in MRL/Ipr lupus mice. The SA-PLGA@antagomiR-7 NPs therapy effectively decreases immunological abnormalities, normalizes splenic B cell subtypes, and suppresses B cell activation. The antagomiR-7 NPs exhibit excellent therapeutic efficiency and high biosafety collectively, which may result in a more effective treatment for SLE.

Aim: This study used the Delphi method and clinical expert discussions to develop an acute paraquat poisoning clinical nursing pathway to standardize acute paraquat poisoning nursing care. Background: In clinical practice, especially in basic-level hospitals, there is no unified standard pattern of treatment and nursing care for patients with paraquat poisoning. Methods: An extensive literature search was used to gather current clinical guidelines for treating paraquat poisoning which were then compiled into a Delphi expert letter of inquiry questionnaire which was sent to a panel of 12 experts. Results: A preliminary draft of the clinical nursing pathway table for acute paraquat poisoning with a standard hospitalization period of 21 days was established, with 6, 23, and 152 classes and I, II, and III indicators determined. The clinical nursing pathway table reduced the randomness of work, avoided nursing interruptions or omissions caused by negligence, and simplified the writing of nursing documents. Conclusions: The clinical nursing pathway can promote and improve the nursing care quality and management efficiency and has good clinical application value.

Summary: Background: Accurate identification of pCR to neoadjuvant chemotherapy (NAC) is essential for determining appropriate surgery strategy and guiding resection extent in breast cancer. However, a non-invasive tool to predict pCR accurately is lacking. Our study aims to develop ensemble learning models using longitudinal multiparametric MRI to predict pCR in breast cancer. Methods: From July 2015 to December 2021, we collected pre-NAC and post-NAC multiparametric MRI sequences per patient. We then extracted 14,676 radiomics and 4096 deep learning features and calculated additional delta-value features. In the primary cohort (n = 409), the inter-class correlation coefficient test, U-test, Boruta and the least absolute shrinkage and selection operator regression were used to select the most significant features for each subtype of breast cancer. Five machine learning classifiers were then developed to predict pCR accurately for each subtype. The ensemble learning strategy was used to integrate the single-modality models. The diagnostic performances of models were evaluated in the three external cohorts (n = 343, 170 and 340, respectively). Findings: A total of 1262 patients with breast cancer from four centers were enrolled in this study, and pCR rates were 10.6% (52/491), 54.3% (323/595) and 37.5% (66/176) in HR+/HER2−, HER2+ and TNBC subtype, respectively. Finally, 20, 15 and 13 features were selected to construct the machine learning models in HR+/HER2−, HER2+ and TNBC subtypes, respectively. The multi-Layer Perception (MLP) yields the best diagnostic performances in all subtypes. For the three subtypes, the stacking model integrating pre-, post- and delta-models yielded the highest AUCs of 0.959, 0.974 and 0.958 in the primary cohort, and AUCs of 0.882–0.908, 0.896–0.929 and 0.837–0.901 in the external validation cohorts, respectively. The stacking model had accuracies of 85.0%–88.9%, sensitivities of 80.0%–86.3%, and specificities of 87.4%–91.5% in the external validation cohorts. Interpretation: Our study established a novel tool to predict the responses of breast cancer to NAC and achieve excellent performance. The models could help to determine post-NAC surgery strategy for breast cancer. Funding: This study is supported by grants from the National Natural Science Foundation of China (82171898, 82103093), the Deng Feng project of high-level hospital construction (DFJHBF202109), the Guangdong Basic and Applied Basic Research Foundation (grant number, 2020A1515010346, 2022A1515012277), the Science and Technology Planning Project of Guangzhou City (202002030236), the Beijing Medical Award Foundation (YXJL-2020-0941-0758), and the Beijing Science and Technology Innovation Medical Development Foundation (KC2022-ZZ-0091-5). Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication.

BackgroundObservational studies have suggested the association between atopic dermatitis (AD) and the risks of autoimmune diseases. It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded.ObjectivesOur study seeks to assess the possibility of AD as a cause of autoimmune diseases, and to estimate the magnitude of the causal effect.MethodsTwo-sample mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) summary-level statistics. Specifically, bidirectional MR analyses were conducted to examine the direction of association of AD with autoimmune diseases; multivariable MR analyses (MVMR1) were used to test the independence of causal association of AD with autoimmune diseases after controlling other atopic disorders (asthma and allergic rhinitis), while MVMR2 analyses were conducted to account for potential confounding factors such as smoking, drinking, and obesity. Genetic instruments for AD (Ncases=22 474) were from the latest GWAS meta-analysis. The GWAS summary data for asthma and allergic rhinitis were obtained from UK Biobank. The GWAS summary data for smoking, alcohol consumption, obesity and autoimmune diseases (alopecia areata, vitiligo, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, and type 1 diabetes) were selected from the largest GWASs available. Causal estimates were derived by the inverse-variance weighted method and verified through a series of sensitivity analyses.ResultsGenetically predicted AD linked to higher risks of rheumatoid arthritis (OR, 1.28; P=0.0068) (ORMVMR1, 1.65; P=0.0020) (ORMVMR2, 1.36; P

ObjectiveTo investigate the characteristics of cardiac involvement due to Immune-mediated Necrotizing Myopathy (IMNM).MethodsPatients diagnosed with Immune-mediated Necrotizing Myopathy (IMNM) who attended the Department of Neurology and the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital between February 2011 and June 2022 were collected. Clinicopathological diagnosis of IMNM was performed according to the criteria established by the European Neuromuscular Center (ENMC). All patients underwent muscle biopsy and Myositis-specific antibodies (MSAs) testing. Information included age, gender, disease duration, intramuscular and extramuscular manifestations, laboratory findings (including creatine kinase, lactate dehydrogenase levels, troponin T, myoglobin and atrial natriuretic peptide), electromyography, skeletal muscle pathology and immunohistochemical staining.ResultsA total of 57 patients were included in this study. Of the serological tests, 56.1% (32/57) were positive for SRP, 21.1% (12/57) were positive for HMGCR and 22.8% (13/57) were seronegative. Thirty patients (52.6%, 30/57) presented with varying degrees of cardiac involvement. We performed ECG in 23 patients and found 6 patients with arrhythmia (26.1%), 12 patients with myocardial ischemia (52.2%), and 7 patients with acute coronary syndrome (ST elevation and non-ST elevation myocardial infarction) (30.4%), and 4 patients with left axis deviation or left ventricular high voltage, suggesting left ventricular hypertrophy (17.4%). Cardiac ultrasound was performed in 14 patients and 3 showed pericardial effusion (21.4%); Decreased left ventricular ejection fraction and atrial enlargement were 2 each; 8 showed a decrease in left ventricular diastolic function (57.1%). In addition, one patient had myocardial edema.ConclusionCardiac involvement is not uncommon in IMNM. However, besides clearly statistically significant differences in the disease course, and in the values of troponin T and myoglobin, our data did not show any statistically significant difference in other features of cardiac involvement between patients with different subtypes of IMNM.

Abstract Introduction Cancer‐associated fibroblasts (CAFs) are correlated with the immunotherapy response. However, the culprits that link CAFs to immunotherapy resistance are still rarely investigated in real‐world studies. Objectives This study aims to systematically assess the landscape of fibroblasts in cancer patients by combining single‐cell and bulk profiling data from pan‐cancer cohorts. We further sought to decipher the expression, survival predictive value and association with immunotherapy response of biglycan (BGN), a proteoglycan in the extracellular matrix, in multiple cohorts. Methods Pan‐cancer tumor bulks and 27 single‐cell RNA sequencing cohorts were enrolled to investigate the correlations and crosstalk between CAFs and tumor or immune cells. Specific secreting factors of CAFs were then identified by expression profiling at tissue microdissection, isolated primary fibroblasts and single‐cell level. The role of BGN was further dissected in additional three bulk and five single‐cell profiling datasets from immunotherapy cohorts and validated in real‐world patients who have received PD‐1 blockade using immunohistochemistry and immunofluorescence. Results CAFs were closely correlated with immune components. Frequent crosstalk between CAFs and other cells was revealed by the CellChat analysis. Single‐cell regulatory network inference and clustering identified common and distinct regulators for CAFs across cancers. The BGN was determined to be a specific secreting factor of CAFs. The BGN served as an unfavourable indicator for overall survival and immunotherapy response. In the real‐world immunotherapy cohort, patients with high BGN levels presented a higher proportion of poor response compared with those with low BGN (46.7% vs. 11.8%) and a lower level of infiltrating CD8+ T cells was also observed. Conclusions We highlighted the importance of CAFs in the tumor microenvironment and revealed that the BGN, which is mainly derived from CAFs, may be applicable in clinical practice and serve as a therapeutic target in immunotherapy resistance.

Abstract Background The CRISPR-Cas12a (formerly Cpf1) system is a versatile gene-editing tool with properties distinct from the broadly used Cas9 system. Features such as recognition of T-rich protospacer-adjacent motif (PAM) and generation of sticky breaks, as well as amenability for multiplex editing in a single crRNA and lower off-target nuclease activity, broaden the targeting scope of available tools and enable more accurate genome editing. However, the widespread use of the nuclease for gene editing, especially in clinical applications, is hindered by insufficient activity and specificity despite previous efforts to improve the system. Currently reported Cas12a variants achieve high activity with a compromise of specificity. Here, we used structure-guided protein engineering to improve both editing efficiency and targeting accuracy of Acidaminococcus sp. Cas12a (AsCas12a) and Lachnospiraceae bacterium Cas12a (LbCas12a). Results We created new AsCas12a variant termed “AsCas12a-Plus” with increased activity (1.5~2.0-fold improvement) and specificity (reducing off-targets from 29 to 23 and specificity index increased from 92% to 94% with 33 sgRNAs), and this property was retained in multiplex editing and transcriptional activation. When used to disrupt the oncogenic BRAFV600E mutant, AsCas12a-Plus showed less off-target activity while maintaining comparable editing efficiency and BRAFV600E cancer cell killing. By introducing the corresponding substitutions into LbCas12a, we also generated LbCas12a-Plus (activity improved ~1.1-fold and off-targets decreased from 20 to 12 while specificity index increased from 78% to 89% with 15 sgRNAs), suggesting this strategy may be generally applicable across Cas12a orthologs. We compared Cas12a-Plus, other variants described in this study, and the reported enCas12a-HF, enCas12a, and Cas12a-ultra, and found that Cas12a-Plus outperformed other variants with a good balance for enhanced activity and improved specificity. Conclusions Our discoveries provide alternative AsCas12a and LbCas12a variants with high specificity and activity, which expand the gene-editing toolbox and can be more suitable for clinical applications.

The safe and stable operation of power transmission and transformation equipment is the foundation of power grid safety, so the prediction of power transmission and transformation equipment fault is particularly important, and the prediction of the characteristic parameters that affect the equipment fault is the core of fault prediction. In this paper, a method for predicting the characteristic parameters of power transmission and transformation equipment based on combination prediction is presented. According to the correlation analysis results of various parameters, the key prediction input data with high correlation degree with the predicted parameters are extracted automatically, and the method library including multiple single-factor prediction models, multi-factor prediction models and combined prediction models is established. The error checking method is used to automatically select the optimal prediction method, and then the characteristic parameters of the parameter are automatically predicted. The test results show that the multi-factor power transmission and transformation equipment fault feature parameter prediction method can improve the accuracy of prediction, and is of great significance to improve the scientific evaluation of equipment health status and the prediction of equipment fault.

Abstract Objective This study explores the relationship between nutritional status and oral health quality of life, the self-efficacy of older inpatients and the correlative factors. Methods In this study, the convenience sampling method was used to select 307 older inpatients in the southern section of the Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October to December 2020 as the main research participants. A mini nutritional assessment questionnaire was used to assess nutritional status, and the Chinese version of a geriatric oral health assessment index questionnaire was used to determine the oral health quality of life. Self-efficacy was assessed by a general self-efficacy scale questionnaire. Descriptive statistics were used to analyse data using the SPSS 22.0 software. Pearson correlation and multiple linear regression analysis were applied to explore the correlation between variables and factors concerned with nutritional status, respectively. Results The results of this study showed that the self-efficacy and oral health quality of life of older inpatients were at a moderate level. Among the patients, 263 had one or more tooth defects, and only 128 had oral restorations or wore dentures. The risk of malnutrition in hospitalised older patients was 37.1%, and the incidence of malnutrition was 13.4%. The risk factors of nutritional status of older patients were age, oral-related quality of life, prealbumin index, self-efficacy, chronic disease, monthly income and tooth defect (P

AIM: To identify the predictive factors and laser photocoagulation associated with the use of silicone oil as endotamponade during primary diabetic vitrectomy. METHODS: The medical and surgical records of 690 patients (798 eyes) who underwent primary diabetic vitrectomy at a tertiary eye hospital in China from January 2018 to December 2018 were reviewed in this retrospective cohort study. The patients' baseline characteristics and preoperative treatments were recorded. The binary Logistic regression model was used to evaluate the risk factors for the use of silicone oil as endotamponade agent during primary vitrectomy for proliferative diabetic retinopathy (PDR)-related complications. RESULTS: Among 690 patients with mean age of 52.1±10.5y (range: 18-85y), 299/690 (43.3%) were female. The 31.6% of the eyes received preoperative laser treatment, and 72.4% of the eyes received preoperative anti-VEGF adjuvant therapy. Non-clearing vitreous haemorrhage (VH) alone or combined with retinal detachment was the main surgical indication (89.5%) for primary vitrectomy. Silicone oil was used as endotamponade in 313 (39.2%) eyes. Lack of preoperative laser treatment [odds ratio (OR) 0.66, 95% confidence interval (CI): 0.48-0.92; P=0.015] and older age (OR 0.96, 95%CI: 0.95-0.98; P

Amber suppression has been widely used to incorporate unnatural amino acids (UNAAs) with unique structures or functional side-chain groups into specific sites of the target protein, which expands the scope of protein-coding chemistry. However, this traditional strategy does not allow multiple-site incorporation of different UNAAs into a single protein, which limits the development of unnatural proteins. To address this challenge, the suppression method using multiple termination codons (TAG, TAA or TGA) was proposed, and cell-free unnatural protein synthesis (CFUPS) system was employed. By the analysis of incorporating 3 different UNAAs (p-propargyloxy-l-phenylalanine, p-azyl-phenylalanine and L-4-Iodophenylalanine) and mass spectrometry, the simultaneous usage of the codons TAG and TAA were suggested for better multiple-site UNAA incorporation. The CFUPS conditions were further optimized for better UNAA incorporation efficiency, including the orthogonal translation system (OTS) components, magnesium ions, and the redox environment. This study established a CFUPS approach based on multiple termination codon suppression to achieve efficient and precise incorporation of different types of UNAAs, thereby synthesizing unnatural proteins with novel physicochemical functions.

Abstract Background Despite significant survival improvement in human epidermal growth factor receptor 2 (HER2) blockade for HER2-positive breast cancer, resistance to anti-HER2 remains inevitable. Subsequent anti-HER2 with continuing trastuzumab beyond progression is acceptable with limited efficacy when other anti-HER2 treatment is unavailable. This single-arm, phase II study (SYSUCC-005) aimed to explore the efficacy of switching mode for HER2-positive refractory metastatic breast cancer. Methods Patients with HER2-positive metastatic breast cancer rapidly progressing during pre-trastuzumab from six hospitals in China were designed to switch to lapatinib 1,250 mg orally once per day continuously plus capecitabine (1,000 mg/m2 orally twice per day on days 1–14) or vinorelbine (25 mg/m2 intravenously once per day on days 1 and 8) of each 21-day cycle. The primary endpoint was progression-free survival (PFS). Results Between January 5, 2015 and May 31, 2020, 159 patients were eligible in this study. The median follow-up was 33.1 months, a median PFS of 8.5 months was achieved. Brain metastases (hazard ratio [HR] = 1.582, 95% confidence interval [CI] 1.019- 2.453, P = 0.041) and ≥ 2 metastatic sites (HR = 1.679, 95% CI 1.151–2.450, P = 0.007) were independent prognostic factors for PFS. The most common grade ≥ 3 adverse events were diarrhea (3.8%) and hand-foot syndrome (9.4%). Conclusion The switching mode showed predominant efficacy, which might be a prior therapeutic option over continuing mode in subsequent anti-HER2 therapy for patients with HER2-positive refractory metastatic breast cancer. Trial registration This trial was registered on ClinicalTrials.gov ( NCT02362958 ) on 13/02/2015.

Clonorchiasis, also known as the liver fluke disease, is caused by eating raw freshwater fish or shrimps that contain Clonorchis sinensis cyst larvae, which mainly involves the hepatobiliary system. Chronic abdominal pain and distention, loss of appetite, and hepatomegaly are the most common clinical manifestation. Persistent infection with Clonorchis sinensis would result in chronic inflammation, epithelial hyperplasia, and periductal fibrosis and even progress to cholangiocarcinoma. Nevertheless, the majority of the infected people are asymptomatic or mildly symptomatic, contributing to its high misdiagnosis rate. Alpha-fetoprotein (AFP) is a well-known biomarker for hepatocellular carcinoma (HCC). A high level of AFP can also be caused by several benign diseases, causing confusion and influencing treatment decisions. So far, clonorchiasis with a markedly elevated level of AFP has been rarely reported. We present a case of clonorchiasis with a high level of AFP in a 52-year-old man. We hope to raise clinical awareness of this food-borne disease. Clonorchiasis should be considered in patients with extremely high levels of AFP, excluding HCC and germ cell tumors, especially if the patient has a history of ingesting raw freshwater fish or shrimps.

This study investigated the effects of bacitracin zinc, potassium diformate and lauric acid on duodenal digestive functions, intestinal morphology and caecal microflora of broilers. A total of 240 male broilers were randomly allotted to four treatments consisting of five replicates with 12 birds per replicate. The dietary treatments were CON group (basal diet), ANT group (basal diet + 40 mg/kg bacitracin zinc), KDF group (basal diet + 1 000 mg/kg potassium diformate), and LA group (basal diet + 500 mg/kg lauric acid). The results showed that the chymotrypsin activity was significantly enhanced on days 21 and 42 in KDF group compared with CON group (P < 0.05), but there were no effects on the activities of trypsin and amylase (P > 0.05). No differences in digestive enzyme activities were found between ANT and LA groups (P > 0.05). Compared with CON group, the villus length and the villus-to-crypt ratio were significantly increased on days 21 and 42, and the crypt depth was significantly decreased in ANT, KDF and LA groups (P < 0.05). Compared with CON group, the supplementation of LA increased the relative abundance of Faecalibacterium on day 21 and the relative abundance of Bacillus on day 42 in caecum, while the supplementation of KDF increased the relative abundance of Faecalibacterium and decreased the relative abundance of Dorea on day 42 in caecum (P < 0.05). In conclusion, the supplementation of KDF enhanced the chymotrypsin activity. Dietary KDF and LA maintained the intestinal morphology by improving the villus length and the villus-to-crypt ratio and decreasing the crypt depth, and regulated the caecal microflora.

Abstract Background Papillary thyroid carcinoma (PTC) is one of most prevalent malignant endocrine neoplasms, and it is associated with a high frequency of BRAF gene mutations, which lead to lymphatic metastasis and distant metastasis that promote tumor progression. The molecular mechanism of PTC and the role of BRAF mutation in PTC progression and development need to be further elucidated. Methods In this study, a comprehensive bioinformatics analysis was performed to identify the differentially expressed genes and signaling pathways in thyroid cancer patients carrying mutant BRAF. Then, we confirmed the prognostic role of WT1 in thyroid cancer patients. Immunohistochemistry was performed to measure the expression profile of WT1 in PTC tissue. Lentivirus shWT1 was transfected into BRAFV600E (mutant) PTC cells to stably inhibit WT1 expression. CCK-8, EdU, immunofluorescence, colony formation, cell migration, cell wound healing, apoptosis and autophagy assays were performed to assess the biological functions of WT1 in BRAFV600E PTC cells. RNA sequencing, immunohistochemistry and immunoblotting were performed to explore the molecular mechanism of WT1 in BRAFV600E PTC cells. Results The results confirmed that “epithelial cell proliferation”, “apoptosis” and “selective autophagy” were closely associated with this BRAF mutant in these thyroid cancer patients. Knocking down BRAF-activated WT1 effectively inhibited the proliferation and migration of BRAFV600E PTC cells. Silencing WT1 significantly inhibited autophagy and promoted the apoptosis of BRAFV600E PTC cells. Mechanistic investigations showed that silencing WT1 expression remarkably suppressed the AKT/mTOR and ERK/P65 signaling pathways in BRAFV600E PTC cells. Conclusion All these results indicate that WT1 is a promising prognostic biomarker and facilitates PTC progression and development of cells carrying the BRAFV600E mutation.

Tetrabromobisphenol A (TBBPA), a commonly utilized brominated flame retardant, is found in many types of abiotic and biotic matrices. TBBPA can increase oxidative stress, disrupt the endocrine system, cause neurodevelopmental disorders and activate peroxisome proliferator-activated receptors to modulate lipid deposits in aquatic animals. However, the toxic mechanism of TBBPA on the gut microbiota and intestinal health remains unclear. Apostichopus japonicus is an ideal model for studying the relationship between environmental contaminants and intestinal health due to its unique capacity for evisceration and quickly regenerated intestine. In the present study, we investigated the toxic mechanism of TBBPA on the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. The results show that TBBPA exposure decreased the health of the regenerated intestine and the enzymatic activities, alpha diversity indices, and the relative abundance of the gut microbiota. Transcriptome analysis shows that TBBPA exposure affected lipid metabolism via the PPAR signaling pathway during the process of intestinal regeneration in A. japonicus, suggesting that TBBPA exposure can affect the composition and function of the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. These results provide a basis for further research on the potential toxicity of TBBPA to the intestinal health in animals.

Urbanization has been shown to cause biodiversity loss. However, its effects on butterfly taxonomic and functional diversity still need to be studied, especially in urban waterfront green spaces where mechanisms of impact still need to be explored. We used butterflies as indicators to study how urbanization affects their taxonomic and functional diversity and identify indicator species in different urban ecological gradient areas. From July to September 2022, we surveyed 10 urban waterfront green spaces in Fuzhou City, China. We recorded 1163 butterflies of 28 species from 6 families. First, we explored the effects of urbanization on butterfly communities and made pairwise comparisons of different urban ecological gradients (α-diversity); secondly, we looked for differences between butterfly communities across urban ecological gradients (β-diversity); finally, we investigated differences in the response of butterfly functional groups to different urban ecological gradient areas and identified ecological indicative species. This study found the following: (1) Urbanization has led to the simplification of butterfly community structure, but there are also favorable factors that support the survival of individual butterflies; (2) Urbanization has led to significant differences in butterfly communities and plant-feeding polyphagous butterfly groups; (3) Urbanization has led to differences in the functional diversity of butterfly diet and activity space groups; (4) We identified five eco-indicator species in different urban ecological gradients.

Beauveria bassiana (B. bassiana) is a broad-spectrum entomopathogenic fungus that can control pests in agriculture and forestry. In this study, encoding ecdysteroid uridine diphosphate glucosyltransferase gene (egt) was successfully screened in B. bassiana on the medium containing 500μg/mL G418 sulfate solution through the protoplast transformation method. This enzyme has the function of 20E (20-hydroxyecdysone) inactivation, thus increasing the mortality of the early instar larvae infected with B. bassiana. In this study, we transformed B. bassiana with the egt gene, which deactivates 20-hydroxyecdysone, a key hormone in insect development. The results showed that transgenic B. bassiana killed more silkworms of the 2nd instar larvae than the wild-type with a shorter LT50 time, which was reduced by approximately 20% (day 1 of the 2nd instar silkworm infection of B. bassiana) and 26.4% (day 2 of the 2nd instar silkworm infection of B. bassiana) compared to the wild-type, and also showed a higher mortality number before molting. The transgenic B. bassiana had a higher coverage of the body surface of silkworms compared to the wild type on the 3rd instar. In summary, improving entomopathogenic fungi using biological methods such as genetic engineering is feasible.

Salicylic acid (SA) serves as a pivotal plant hormone involved in regulating plant defense mechanisms against biotic stresses, but the extent of its biological significance in relation to peanut resistance is currently lacking. This study elucidated the involvement of salicylic acid (SA) in conferring broad-spectrum disease resistance in peanuts through the experimental approach of inoculating SA-treated leaves. In several other plants, the salicylate hydroxylase genes are the typical susceptible genes (S genes). Here, we characterized two SA hydroxylase genes (AhS5H1 and AhS5H2) as the first S genes in peanut. Recombinant AhS5H proteins catalyzed SA in vitro, and showed SA 5-ydroxylase (S5H) activity. Overexpression of AhS5H1 or AhS5H2 decreased SA content and increased 2,5-DHBA levels in Arabidopsis, suggesting that both enzymes had a similar role in planta. Moreover, overexpression of each AhS5H gene increased susceptibility to Pst DC3000. Analysis of the transcript levels of defense-related genes indicated that the expression of AhS5H genes, AhNPR1 and AhPR10 was simultaneously induced by chitin. Overexpression of each AhS5H in Arabidopsis abolished the induction of AtPR1 or AtPR2 upon chitin treatment. Eventually, AhS5H2 expression levels were highly correlated with SA content in different tissues of peanut. Hence, the expression of AhS5H1 and AhS5H2 was tissue-specific.

The application of mulching film has significantly contributed to improving agricultural output and benefits, but residual film has caused severe impacts on agricultural production and the environment. In order to realize the accurate recycling of agricultural residual film, the detection of residual film is the first problem to be solved. The difference in color and texture between residual film and bare soil is not obvious, and residual film is of various sizes and morphologies. To solve these problems, the paper proposes a method for detecting residual film in agricultural fields that uses the attention mechanism. First, a two-stage pre-training approach with strengthened memory is proposed to enable the model to better understand the residual film features with limited data. Second, a multi-scale feature fusion module with adaptive weights is proposed to enhance the recognition of small targets of residual film by using attention. Finally, an inter-feature cross-attention mechanism that can realize full interaction between shallow and deep feature information to reduce the useless noise extracted from residual film images is designed. The experimental results on a self-made residual film dataset show that the improved model improves precision, recall, and mAP by 5.39%, 2.02%, and 3.95%, respectively, compared with the original model, and it also outperforms other recent detection models. The method provides strong technical support for accurately identifying farmland residual film and has the potential to be applied to mechanical equipment for the recycling of residual film.

Eucalyptus is a genus of over 900 species and hybrids, and many of them are valuable fast-growing hardwoods. Due to its economic importance, Eucalyptus is one of the early tree species whose genomes were deciphered. However, the lack of efficient genetic transformation systems severely restricts the functional genomic research on the plant. The success of Eucalyptus regeneration and transformation depends greatly on the genotypes and explants. In this study, we systematically screened 26 genotypes from 12 Eucalyptus species in an attempt to obtain Eucalyptus genotypes with high regeneration potential. We developed two common regeneration media that can be applied to most tested Eucalyptus genotypes for both seeding hypocotyls and cloned internodes as explants. We then implemented DsRed2 as a visual marker for genetic transformation efficiency test. Our results suggest that E. camaldulen and E. robusta are amenable for genetic transformation. Finally, we successfully set up a stable Agrobacterium-mediated genetic transformation procedure for both E. camaldulen and E. robusta using seeding hypocotyls and cloned internodes respectively. Taken together, our study provides valuable means for vegetative propagation, gene transformation, CRISPR based gene mutagenesis, activation and suppression, as well as functional characterization of genes in Eucalyptus.

This article studies the control problem of the discrete-time Markov jump systems (MJSs). First, the asynchronous switching between the plant modes and the controller modes is taken into consideration. To handle this issue, the estimated modes are utilized in the controller design. Second, in order to reduce the frequency of data transmission in the control system, a dynamic event-triggered communication scheme is introduced into the controller-to-actuator channel. Third, the exogenous disturbance is considered and the $l_{2}-l_{\infty }$ performance index is introduced. In addition, all the states are unavailable and only the output signals are used for the feedback design. The highlight of this study is that a more general case is considered, in which both the plant modes and the states are assumed to be unavailable. The fundamental issue is to determine the feedback gains and the event-triggering matrix simultaneously such that the closed-loop MJSs are stochastically stabilized with a certain level of $l_{2}-l_{\infty }$ performance. By constructing a mode-dependent Lyapunov function, a set of sufficient conditions is derived and the control algorithm is developed. At last, a numerical example and a DC-DC switched boost converter circuit are given to show the effectiveness and practicability of the proposed control technique.

Background. Intraoperative radiotherapy (IORT) is a novel promising technology that may replace external beam radiation therapy (EBRT) as boost for patients receiving breast-conserving surgery. To better evaluate the efficacy of IORT using low-kilovoltage (low-kV) X-rays as boost, we presented this meta-analysis according to the PRISMA checklist. Methods. Studies reported survival outcomes of intraoperative radiation using low-kilovoltage X-rays system (Intrabeam®, Carl Zeiss Meditec, Dublin, CA, USA) as boost were identified through electronic bibliographic database: PUBMED. The meta-analysis module in Stata (16.0) is used to pool the studies. A Poisson regression model is used to predict a 5-year local recurrence rate. Results. Twelve studies including 3006 cases were included in the final analysis, with a median follow-up of 55 months weighted by sample size. The pooled local recurrence rate is 0.39% per person-year (95% CI: 0.15%–0.71%), with a low degree of heterogeneity (I2 = 0%). The predicted 5-year local recurrence rate was 3.45%. No difference in pooled local recurrence rate was found between non-neoadjuvant patients studies and neoadjuvant patients studies (0.41% per person-year vs. 0.58% per person-year, P=0.580). Conclusions. This study shows that low-kV IORT is an effective method as boost in breast cancer patients, with a low pooled local recurrence rate and low predicted 5-year local recurrence rate. Besides, no difference in the local recurrence rate was found between non-neoadjuvant patients studies and neoadjuvant patients studies. Low-kV IORT boost may be a promising alternative to EBRT boost in the future, which is being tested in the ongoing TARGIT-B trial.

Objective. To compare eye-related quality of life between Chinese children wearing orthokeratology (OK) contact lenses and single-vision spectacles (SVS) using the Pediatric Eye Questionnaire (PedEyeQ) and to evaluate the impact of different myopia correction methods on children and their parents. Methods. Children aged 12–17 years and their parents/legal guardians were recruited. The children’s myopia ranged from −0.50 to −5.00 diopters (D), and their astigmatism was 0.05). Conclusion. Compared with children wearing SVS, children wearing OK contact lenses have better functional vision and eye-related quality of life. Moreover, OK contact lens has a better correction effect, higher acceptance rates, and less impact on parents and families than SVS.

Vitellogenin receptors (VgRs) transport vitellogenin (Vg) into oocytes, thereby promoting egg growth and embryonic development. VgRs recognize and transport multiple ligands in oviparous animals, but their role in insects is rarely reported. In this study, we investigated whether Bombyx mori VgR (BmVgR) binds and transports lipoprotein-1 (BmLP1) and lipoprotein-7 (BmLP7) of the 30 kDa lipoproteins (30 K proteins), which are essential for egg formation and embryonic development in B. mori. Protein sequence analysis showed BmLP7, similar to reported lipoprotein-3 (BmLP3), contains the cell-penetrating peptides and Cysteine position, while BmLP1 has not. Assays using Spodoptera frugiperda ovary cells (sf9) indicated the direct entry of BmLP7 into the cells, whereas BmLP1 failed to enter. However, co-immunoprecipitation (Co-IP) assays indicated that BmVgR could bind BmLP1. Western blotting and immunofluorescence assays further revealed that over-expressed BmVgR could transport BmLP1 into sf9 cells. Co-IP assays showed that SE11C (comprising LBD1+EGF1+OTC domains of BmVgR) or SE22C (comprising LBD2+EGF2+OTC domains of BmVgR) could bind BmLP1. Over-expressed SE11C or SE22C could also transport BmLP1 into sf9 cells. Western blotting revealed that the ability of SE11C to transport BmLP1 might be stronger than that of SE22C. In the vit mutant with BmVgR gene mutation (vit/vit), SDS-PAGE and western blotting showed the content of BmLP1 in the ovary, like BmVg, was lower than that in the normal silkworm. When transgenic with hsp70 promoter over-expressed BmVgR in the vit mutant, we found that the phenotype of the vit mutant was partly rescued after heat treatment. And contents of BmLP1 and BmVg in vit mutant over-expressed BmVgR were higher than in the vit mutant. We conclude that BmVgR and its two repeat domains could bind and transport BmLP1 into the oocytes of the silkworm, besides BmVg. These results will provide a reference for studying the molecular mechanism of VgR transporting ligands in insects.

IntroductionPrimary intracranial malignant lymphoma (PIML) is a rare form of lymphoma that most often occurs in the brain and has an extremely low 5-year survival rate. Although chemotherapy and radiotherapy are widely used in the clinical management of PIML, the choice of treatment regimen and the actual circumstances of patients remain challenges when assessing survival rates in different patients.MethodsConsidering this, we obtained clinical treatment and survival information from the Surveillance, Epidemiology, and End Results database (SEER) on patients with lymphoma, the primary site of which was the brain, and performed statistical analyses of the demographic characteristics. Survival analyses were performed using the Kaplan–Meier method, and univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors.ResultWe identified age, pathology, the Ann Arbor stage, and treatment as the risk factors affecting patient prognosis. The areas under the curve (AUCs) for overall survival at 1, 3, and 5 years were 0.8, 0.818, and 0.81, respectively. The AUCs for cancer-specific survival at 1, 3, and 5 years were 0.8, 0.79, and 0.79. The prediction ability in the development and verification cohorts was in good agreement with the actual values, while we plotted the clinical decision curves for the model, suggesting that the nomogram can provide benefits for clinical decision-making.ConclusionOur model provides a prognostic guide for patients with PIML and a reliable basis for clinicians.

BackgroundPrevious experimental studies have reported an association between microcystin-LR (MC-LR) and glucose homeostasis, but whether exposure to MC-LR is a risk factor for the pathogenesis of gestational diabetes mellitus (GDM) requires further epidemiological study. This study aims to explore the effects of MC-LR on GDM.MethodsA prospective nested case-control study was performed in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. The two independent samples t-test, or chi-square test was used to compare the difference between the GDM group and the non-GDM group. Binary logistic regression was used to obtain odds ratios (ORs) by controlling for confounders.ResultsThe cumulative incidence of GDM in our sample was 13.7%. The detection rate of MC-LR in the GDM group were significantly higher than those in the control group (44.2% vs. 29.4%; p=0.007). Our results show that an elevated serum MC-LR level in the first trimester of pregnancy was related to an increased risk of GDM (OR: 1.924; 95% CI: 1.092-3.391; p30 years, lower income, higher education, none passive smoking, and more likely to be multiparous.ConclusionsOur data reveals that serum MC-LR level in the first trimester is independently associated with GDM.

The unclear molecule structures-compatibility relationship obstructs the enhancement of compatibility between polysiloxane and epoxy resins. Herein, we reveal the molecule structures-compatibility relationship and propose a synergistic design strategy to improve compatibility. Taking three typical terminal molecular structures (-NH2 group, –OH group and epoxy group) as examples, it is found that the solubility parameter and binding energy parameter of polysiloxanes are dominated by van der Waals interaction, which is closely related to the number of terminal atoms. The –NH2 group is with the strongest electrostatic interaction due to the strong electrostatic potential and low steric hindrance. On this basis, silicone prepolymer is successfully synthetized to improve compatibility through synergistically enhancing the van der Waals interaction and electrostatic interaction by increasing the number of terminal atoms and introducing –NH2 group. Consequently, Si element is uniformly distributed in the epoxy resin with silicone prepolymer, which indicates highly compatible effects. The hydrophobicity of epoxy resin is also significantly improved about 19.03% by the silicone prepolymer. The established molecular structure-compatibility relationship and proposed synergistic design strategy open up an alternative design concept for compatibility improvement in multiphase organic polymers and can be applied in insulation, moisture-proof and other fields.

The application of waste materials in the concrete composite is a great contribution to preserving natural resources and enhancing sustainable greener development in the construction industry. This study used Palm Oil Clinker (POC) and steel fibers to manufacture high-strength lightweight concrete (HSLWC). The POC is basically a byproduct of a palm oil industry, which was utilized as coarse aggregates and supplementary cementitious materials in the concrete. The noteworthy brittleness and lower tensile strain and strength of HSLWC were overcome by adding hooked end steel fibers. A total of six different concrete mixes by varying the volume of hooked end steel fibers, e.g., 0, 0.25, 0.50, 0.75, 1.0 and 1.50% of the total volume of the concrete were prepared. The HSLWC with 0% steel fibers was used as a reference. The physical and mechanical characteristics of the HSLWC, such as workability, density, compressive and splitting tensile strength, modulus of rupture (MOR), modulus of elasticity (MOE), stress–strain characteristics along with UPV, sorptivity and water absorption test were conducted. Compared to the reference specimen, the HSLWC increased the compressive and tensile strength, MOR, and MOE by 19%, 172%, 176% and 40%, respectively. Besides, the HSLWC exhibited ductility and had enough energy absorption capacity before failure.

ObjectivesThis study aimed to examine the audiological characteristics and validity of predicting outcomes of cochlear implants (CIs) in children with cochlear nerve deficiency (CND) based on the internal auditory meatus (IAM) nerve grading system.MethodsThe audiological characteristics of 188 ears in 105 children diagnosed with CND were analyzed based on the IAM nerve grading system. In addition, 42 children with CND who underwent CI were also divided into four groups based on the system, and their auditory and speech performance at baseline (preoperative) and 6, 12, and 24 months after CI were analyzed and compared with those of the control group (n = 24) with a normal cochlear nerve (CN) and CI.ResultsThe audiological test results showed no significant differences among the four CND groups in terms of elicited rates of distortion product otoacoustic emission (DPOAE) (p = 1.000), auditory brainstem response (ABR) (p = 0.611), and cochlear microphonic (CM) (p = 0.167). Hearing in the CND IV group was significantly better than that in the CND I group (p < 0.05). In children with CI, the auditory and speech performance of the control group was significantly higher than all CND groups from 6 to 24 months (p < 0.05) and 12 to 24 months (p < 0.05), respectively. Meanwhile, there were no significant differences between each pair group in the four CND groups (p > 0.05).ConclusionChildren with CND, including those in whom the CN was not visualized by MRI, can benefit from CI. Additionally, the IAM nerve grading system could not predict the outcomes of CI in children with CND.

Background: It is critical to train future nursing managers in advance for the prospective development of healthcare organizations, but a widely recognized curriculum content structure for leadership and management competency development for nurturing future nurse managers was lacking in China. Objective: To establish a curriculum content structure for the leadership and management competency cultivation for future nurse managers in Chinese healthcare setting. Methods: A modified Delphi study was conducted. 22 experts who have in-depth knowledge of nursing leadership and management from 4 main geographical regions in China were included. The initial curriculum content structure was constructed based on a previous qualitative study and two team meetings. Subsequently, a two-round Delphi survey was conducted with 22 panelists in the first round and 19 in the second round. Scores of importance and textual comments were collected and used to judge the achievement of consensus. Results: After the two-round Delphi process, consensus was reached, as each item was rated ≥4 by 84.21–100% of the experts and each one had a coefficient of variance (CV) ≤ 0.174. The finalized curriculum content contains 9 modules and 27 items. Conclusions: This study formed a curriculum content structure for leadership and management competency training for nurses preparing for managerial roles, which contribute to the establishment of a nursing management talent pipeline to meet the needs of healthcare institutions for contemporary nurse managers.

Ethnopharmacological relevance: Hepatic fibrosis (HF) occurs in response to chronic liver injury and may easily develop into irreversible liver cirrhosis or even liver cancer. Amydrium hainanense water extract (AHWE) is a water-soluble component extracted from the Yao medicine Amydrium hainanense (H.Li, Y.Shiao & S.L.Tseng) H.Li, which is commonly used for treating inflammatory diseases in folk. Previous evidence suggested that AHWE significantly inhibited hepatic stellate cell activation. However, little is known regarding the therapeutic effect of AHWE in HF and its underlying action mechanism.Objective: Investigation of the therapeutic effect of AHWE in HF and its underlying mechanism.Methods: The therapeutic effect of AHWE was tested in vivo using an HF mouse model via an intraperitoneal injection of carbon tetrachloride (CCl4). Histological evaluation of liver injury and fibrosis were tested by H&E staining and Masson’s trichrome staining. Serum levels of ALT, AST, collagen type I (Col I), and hydroxyproline (HYP) were measured. The mRNA expression of liver fibrotic and inflammatory genes were tested, and the protein levels of alpha smooth muscle actin (α-SMA) and signal transducers and activators of transcription 3 (STAT3) were analyzed. The in vitro experiments were conducted using HSC-T6 and RAW264.7 cell lines.Results: Treatment with AHWE significantly reversed histopathological liver damage and liver function abnormalities in CCl4 mouse model. Also, the serum levels of ALT, AST, Col I, and HYP in CCl4-induced HF mice were improved in AHWE treatment. Further, AHWE showed a remarkable inhibitory effect on the expression of fibrosis markers (Acta2, Col1a1, and Col3a1) and inflammatory factors (Stat3, Tnfa, Il6, and Il1b) induced by CCl4. The results of in vitro experiments were consistent with those obtained in vivo. In addition, it is shown that STAT3 signaling was involved in the anti-fibrotic effects of AHWE as evidenced by STAT3 overexpression.Conclusion: The present study proposed a novel ethnomedicine for HF and suggested the underlying role of STAT3 signaling pathway regulation in this anti-fibrotic effect of the proposed medicine. These findings would serve as solid scientific evidence in support of the development of AHWE as a novel alternative or complementary therapy for HF prevention and treatment.

BackgroundPatients with acute toxic hemoperfusion are prone to deep vein thrombosis. However, there is no risk assessment model for thrombosis in patients with acute toxic hemoperfusion. Therefore, we compared three commonly used risk assessment models for deep vein thrombosis to determine the model most suitable for assessment of deep vein thrombosis in patients with acute toxic hemoperfusion.MethodsCaprini, Autar, and Padua thrombosis risk assessment models were used to assess the risk of deep vein thrombosis in patients with acute poisoning and hemoperfusion admitted to a grade A hospital in Shandong province from October 2017 to February 2019. The predictive values of the three models were compared using receiver operating characteristic (ROC) curve analysis.ResultsThe risk assessment model scores of Caprini, Autar, and Padua were 7.55 ± 1.76, 8.63 ± 2.36, and 3.92 ± 0.55, respectively. The Caprini risk assessment model was significantly different (p < 0.05) in high-risk patients in the thrombus and non-thrombotic groups; the difference between the other two models was not significant (p > 0.05). The areas under the ROC curve of the Caprini, Autar, and Padua risk assessment models were 0.673, 0.585, and 0.535, respectively. The difference in areas under the ROC curve between the Caprini risk assessment model and the Autar risk assessment model as well as the Padua risk assessment model was significant (p < 0.05), but the areas under the ROC curve of the Autar risk assessment model and the Padua risk assessment model were not statistically significant (p > 0.05). The Caprini risk assessment model had a sensitivity of 91.9%, specificity of 33.1%, and a Youden index of 0.249. The sensitivity and specificity of Autar’s risk assessment model were 37.0 and 77.2%, respectively, and the Youden index was 0.141. The Padua risk assessment model had a sensitivity of 91.3%, specificity of 15.0%, and a Youden index of 0.063.ConclusionThe three thrombosis risk assessment models were not suitable for patients with acute poisoning and hemoperfusion.

ObjectiveTo raise awareness of Cytochrome P450 Oxidoreductase Deficiency (PORD, a rare form of congenital adrenal hyperplasia (CAH), through a case of pregnant woman with virilization symptoms.Case descriptionA 30-year-old Chinese woman was referred to hospital after 7 years of presenting signs of virilization, including voice deepening, acromegaly, hirsutism, clitoromegaly, and acne. These symptoms appeared since her third gestation. Her second birth died 9 hours after birth and had signs of clitoris hypertrophy. Her third born was a son who presented with flat nose, radius and humerus bone malformation, and small penis at birth. Panel of POR-related genetic tests revealed that the patient carried c.1370 G>A (p.R457H), which is a POR heterozygous gene, while her husband carried a POR heterozygous gene as well, c.1379 C>A (p.S460Y). Two heterozygous mutations of the POR were found in her son: c.1370 G>A and c.1379 C>A. In PORD, c.1370 G>A (p.R457H) was reported as a susceptible gene, while c.1379 C>A (p.S460Y) has not been reported as responsible for the disease so far.Discussion and literature reviewPORD is a rare form of CAH and caused by POR gene mutations. Most PORD patients are identified and diagnosed in pediatrics department. Internal medicine and obstetrics physicians are unfamiliar with the disease. As clinical manifestations are diverse, PORD could be easy to miss or to be misdiagnosed. Typical clinical manifestation includes adrenal insufficiency-related symptoms, such as bone malformations and sexual development disorders. PORD is diagnosed through genetic testing. Investigations of steroid metabolic products in urine through gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry are also helpful for the diagnosis, but neither of them are widely available in China. In this case, the patient had a history of infertility, and her third child was born with congenital defect and carried a PORD-related gene. In general clinical practice, if a pregnant woman presents with abnormal virilization symptoms, CAH possibilities should be considered, including rare causes such as PORD.ConclusionPORD is a rare autosomal recessive genetic disease. We summarised the clinical characteristics and genotypes that were previously reported in the Chinese population and identified a novel mutation.

Objective Acupuncture is emerging as a potential therapy for relieving pain, but the effectiveness of acupuncture for relieving low back and/or pelvic pain (LBPP) during the pregnancy remains controversial. This meta-analysis aims to investigate the effects of acupuncture on pain, functional status and quality of life for women with LBPP pain during the pregnancy.Design Systematic review and meta-analysis.Data sources The PubMed, EMBASE databases, Web of Science and Cochrane Library were searched for relevant randomised controlled trials (RCTs) from inception to 15 January 2022.Eligibility criteria for selecting studies RCTs evaluating the effects of acupuncture on LBPP during the pregnancy were included.Data extraction and synthesis The data extraction and study quality assessment were independently performed by three reviewers. The mean differences (MDs) with 95% CIs for pooled data were calculated. We assessed the confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework.Main outcomes and measures The primary outcomes were pain, functional status and quality of life. The secondary outcomes were overall effects (a questionnaire at a post-treatment visit within a week after the last treatment to determine the number of people who received good or excellent help), analgesic consumption, Apgar scores >7 at 5 min, adverse events, gestational age at birth, induction of labour and mode of birth.Results This meta-analysis included 10 studies, reporting on a total of 1040 women. Overall, acupuncture significantly relieved pain during pregnancy (MD=1.70, 95% CI: (0.95 to 2.45), p