Colorimetric detection of neomycin sulfate in serum based on ultra-small gold nanoparticles with peroxidase-like activity.

Neomycin sulfate (NEO) is a kind of aminoglycoside antibiotics. Because of its strong ototoxicity, nephrotoxicity and other side effects, its content in the body should be strictly monitored during use. In this paper, a rapid colorimetric detection method for NEO based on ultrasmall polyvinylpyrrolidone modified gold nanoparticles (PVP/Au NPs) with peroxidase-like activity was developed. Firstly, ultra small PVP/Au NPs with weak peroxidase-like activity were synthetized. When they were mixed with NEO, strong hydrogen bonds were formed between NEO and PVP, resulting in the aggregation of PVP/Au NPs, and the aggregated PVP/Au NPs showed stronger peroxidase-like activity. Therefore, rapid colorimetric detection of NEO was achieved by utilizing the enhanced peroxidase-like activity mechanism caused by the aggregation of ultra small PVP/Au NPs. The naked eye detection limit of this method is 50 nM. Within the range of 1 nM-300 nM, there was a good linear relationship between NEO concentration and the change in absorbance intensity of PVP/Au NPs-H2O2-TMB solution at 652 nm, with the regression curve of y = 0.0045x + 0.0525 (R2 = 0.998), and the detection limit is 1 nM. In addition, this method was successfully applied to the detection of NEO in mouse serum. The recoveries were 104.4 % -107.6 % compared with HPLC assay results, indicating that this method for NEO detection based on PVP/Au NPs has great potential in actual detection of NEO in serum.

Shared Genetic Architecture Among Gastrointestinal Diseases, Schizophrenia, and Brain Subcortical Volumes.

BACKGROUND AND HYPOTHESIS: The gut-brain axis plays important roles in both gastrointestinal diseases (GI diseases) and schizophrenia (SCZ). Moreover, both GI diseases and SCZ exhibit notable abnormalities in brain subcortical volumes. However, the genetic mechanisms underlying the comorbidity of these diseases and the shared alterations in brain subcortical volumes remain unclear. STUDY DESIGN: Using the genome-wide association studies data of SCZ, 14 brain subcortical volumes, and 8 GI diseases, the global polygenic overlap and local genetic correlations were identified, as well as the shared genetic variants among those phenotypes. Furthermore, we conducted multi-trait colocalization analyses to bolster our findings. Functional annotations, cell-type enrichment, and protein-protein interaction (PPI) analyses were carried out to reveal the critical etiology and pathology mechanisms. STUDY RESULTS: The global polygenic overlap and local genetic correlations informed the close relationships between SCZ and both GI diseases and brain subcortical volumes. Moreover, 84 unique lead-shared variants were identified. The associated genes were linked to vital biological processes within the immune system. Additionally, significant correlations were observed with key immune cells and the PPI analysis identified several histone-associated hub genes. These findings highlighted the pivotal roles played by the immune system for both SCZ and GI diseases, along with the shared alterations in brain subcortical volumes. CONCLUSIONS: These findings revealed the shared genetic architecture contributing to SCZ and GI diseases, as well as their shared alterations in brain subcortical volumes. These insights have substantial implications for the concurrent development of intervention and therapy targets for these diseases.

A segmentation-based algorithm for classification of benign and malignancy Thyroid nodules with multi-feature information.

The aim of this study is to propose a new diagnostic model based on "segmentation + classification" to improve the routine screening of Thyroid nodule ultrasonography by utilizing the key domain knowledge of medical diagnostic tasks. A Multi-scale segmentation network based on a pyramidal pooling structure of multi-parallel void spaces is proposed. First, in the segmentation network, the exact information of the underlying feature space is obtained by an Attention Gate. Second, the inflated convolutional part of Atrous Spatial Pyramid Pooling (ASPP) is cascaded for multiple downsampling. Finally, a three-branch classification network combined with expert knowledge is designed, drawing on doctors' clinical diagnosis experience, to extract features from the original image of the nodule, the regional image of the nodule, and the edge image of the nodule, respectively, and to improve the classification accuracy of the model by utilizing the Coordinate attention (CA) mechanism and cross-level feature fusion. The Multi-scale segmentation network achieves 94.27%, 93.90% and 88.85% of mean precision (mPA), Dice value (Dice) and mean joint intersection (MIoU), respectively, and the accuracy, specificity and sensitivity of the classification network reaches 86.07%, 81.34% and 90.19%, respectively. Comparison tests show that this method outperforms the U-Net, AGU-Net and DeepLab V3+ classical models as well as the nnU-Net, Swin UNetr and MedFormer models that have emerged in recent years. This algorithm, as an auxiliary diagnostic tool, can help physicians more accurately assess the benign or malignant nature of Thyroid nodules. It can provide objective quantitative indicators, reduce the bias of subjective judgment, and improve the consistency and accuracy of diagnosis. Codes and models are available at https://github.com/enheliang/Thyroid-Segmentation-Network.git.

miR-338-5p regulated the NF-κB/MAPK pathway to alleviate inflammation and oxidative stress by targeting IL-6 in rats with atrial fibrillation.

The aim of this study was to investigate the functional effect of miR-338-5p targeting IL-6 on NF-κB/MAPK pathway-mediated inflammation and oxidative stress in atrial fibrillation (AF) rats. AF model rats were generated by tail vein injection of 0.1 mL Ach-CaCl2 mixture. The overexpression and suppression of miR-338-5p were established by injecting a miR-338-5p-agomir and a miR-338-5p-antagomir, respectively, into AF rats. Cardiac morphological changes were detected by H&E and Masson staining. The levels of ROS, SOD, T-AOC, IL-6, IL-1ß, and TNF-α were detected via ELISA. Dual luciferase assays, qRT‒PCR, and western blotting were used to verify that miR-338-5p targets IL-6. The expression of NF-κB/MAPK pathway proteins was detected by western blot. Overexpression of miR-338-5p ameliorated heart damage in AF rats. Increased miR-338-5p reduced the levels of CK, CK-MB, and cTnT to alleviate myocardial injury. Furthermore, overexpression of miR-338-5p relieved inflammation and oxidative stress by downregulating SOD and T-AOC and upregulating IL-6, IL-1ß, TNF-α, and ROS. Further research revealed that upregulation of miR-338-5p reduced the protein levels of p-p38, p-p65 and p-ERK1/2. The opposite results were obtained following miR-338-5p-antagomir treatment. Taken together, these findings indicate that the upregulation of miR-338-5p alleviated inflammation and oxidative stress by targeting IL-6 to inhibit the NF-κB/MAPK pathway, thus providing a new therapeutic target for AF.

In-situ dynamic catalysis electrode electrolyte interphase enabling Mg2+ insertion in 2D metal-organic polymer for high-capacity and long-lifespan magnesium batteries.

Rechargeable magnesium battery is regarded as the promising candidate for the next generation of high-specific-energy storage systems. Nevertheless, issues related to severe Mg-Cl dissociation at the electrolyte-electrode interface impede the insertion of Mg2+ into most materials, leading to severe polarization and low utilization of Mg-storage electrodes. In this study, a metal-organic polymer (MOP) Ni-TABQ (Ni-coordinated tetramino-benzoquinone) with superior surface catalytic activity is proposed to achieve the high-capacity Mg-MOP battery. The layered Ni-TABQ cathode, featuring a unique 2D π-d linear conjugated structure, effectively reduces the dissociation energy of MgxCly clusters at the Janus interface, thereby facilitating Mg2+ insertion. Due to the high utilization of active sites, Ni-TABQ achieves high capacities of 410 mAh/g at 200 mA g-1, attributable to a four-electron redox process involving two redox centers, benzoid carbonyls, and imines. This research highlights the importance of surface electrochemical processes in rechargeable magnesium batteries and paves the way for future development in multivalent metal-ion batteries.

Effects of different observed datasets on the calibration of crop model parameters with GLUE: A case study using the CROPGRO-Soybean phenological model.

Suitable combinations of observed datasets for estimating crop model parameters can reduce the computational cost while ensuring accuracy. This study aims to explore the quantitative influence of different combinations of the observed phenological stages on estimation of cultivar-specific parameters (CPSs). We used the CROPGRO-Soybean phenological model (CSPM) as a case study in combination with the Generalized Likelihood Uncertainty Estimation (GLUE) method. Different combinations of four observed phenological stages, including initial flowering, initial pod, initial grain, and initial maturity stages for five soybean cultivars from Exp. 1 and Exp. 3 described in Table 2 are respectively used to calibrate the CSPs. The CSPM, driven by the optimized CSPs, is then evaluated against two independent phenological datasets from Exp. 2 and Exp. 4 described in Table 2. Root means square error (RMSE) (mean absolute error (MAE), coefficient of determination (R2), and Nash Sutcliffe model efficiency (NSE)) are 15.50 (14.63, 0.96, 0.42), 4.76 (3.92, 0.97, 0.95), 4.69 (3.72, 0.98, 0.95), 3.91 (3.40, 0.99, 0.96) and 12.54 (11.67, 0.95, 0.60), 5.07 (4.61, 0.98, 0.93), 4.97 (4.28, 0.97, 0.94), 4.58 (4.02, 0.98, 0.95) for using one, two, three, and four observed phenological stages in the CSPs estimation. The evaluation results suggest that RMSE and MAE decrease, and R2 and NSE increase with the increase in the number of observed phenological stages used for parameter calibration. However, there is no significant reduction in the RMSEs (MAEs, NSEs) using two, three, and four observed stages. Relatively reliable optimized CSPs for CSMP are obtained by using at least two observed phenological stages balancing calibration effect and computational cost. These findings provide new insight into parameter estimation of crop models.

The ABCF ATPase New1 resolves translation termination defects associated with specific tRNAArg and tRNALys isoacceptors in the P site.

The efficiency of translation termination is determined by the nature of the stop codon as well as its context. In eukaryotes, recognition of the A-site stop codon and release of the polypeptide are mediated by release factors eRF1 and eRF3, respectively. Translation termination is modulated by other factors which either directly interact with release factors or bind to the E-site and modulate the activity of the peptidyl transferase center. Previous studies suggested that the Saccharomyces cerevisiae ABCF ATPase New1 is involved in translation termination and/or ribosome recycling, however, the exact function remained unclear. Here, we have applied 5PSeq, single-particle cryo-EM and readthrough reporter assays to provide insight into the biological function of New1. We show that the lack of New1 results in ribosomal stalling at stop codons preceded by a lysine or arginine codon and that the stalling is not defined by the nature of the C-terminal amino acid but rather by the identity of the tRNA isoacceptor in the P-site. Collectively, our results suggest that translation termination is inefficient when ribosomes have specific tRNA isoacceptors in the P-site and that the recruitment of New1 rescues ribosomes at these problematic termination contexts.

Efficacy and safety of robotic vs. laparoscopic gastrectomy for patients with gastric cancer: systematic review and meta-analysis.

BACKGROUND: The emergence of robotic surgical systems compensated for the technological shortcomings of laparoscopic approaches. However, whether robotic gastrectomy (RG) has better perioperative outcomes and survival than laparoscopic gastrectomy (LG) for gastric cancer is still unclear but increasingly drawing attention. MATERIALS AND METHODS: In this systematic review and meta-analysis, we searched the PubMed, EMBASE, Web of Science, and Cochrane Library as of January 20, 2024 and referenced list of eligible articles for all published studies comparing RG and LG for patients with gastric cancer, Data on study characteristics, individual characteristics, and outcome parameters were extracted. The quality of studies was assessed using the Revised Cochrane risk-of-bias 2 tool and the risk of bias in non-randomized studies of interventions tool. The main outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS: We identified 3641 articles, of which 72 studies (30081 patients) were included in the meta-analysis. Compared with LG, RG was associated with higher OS [hazard ratio (HR)=0.89, 95% CI=0.83 to 0.96), lower rate of overall postoperative complications [odds ratio (OR)=0.77, 95% CI=0.71 to 0.84], longer operating time [mean difference (MD)=35.53, 95% CI=29.23 to 41.83], less estimated blood loss (MD=-37.45, 95% CI=-46.24 to -28.67), a higher number of retrieved lymph nodes (MD=1.88, 95% CI=0.77 to 3.00), faster postoperative recovery, and lower rate of conversion (OR=0.44, 95% CI=0.36 to 0.55). Mortality and DFS were not significantly different between the two groups. The subgroup of meta-analysis results also showed the advantages of robotic surgery over laparoscopic surgery in intracorporeal reconstruction, total gastrectomy, Ⅰ/Ⅱ stage, and BMI≥25, especially for patients with stage Ⅰ/Ⅱ, there is better overall survival and disease-free survival. CONCLUSION: Our findings point to robotic surgery having great benefits compared with laparoscopic surgery in gastric cancer. Our study may help inform decision-making in applying robotic surgical systems to clinical treatment.

The rehabilitation efficacy of diaphragmatic breathing combined with limb coordination training for lower limb lymphedema following gynecologic cancer surgery.

Objective: To investigate the impact of diaphragmatic breathing combined with limb training on lower limb lymphedema following surgery for gynecological cancer. Methods: From January 2022 to May 2022, 60 patients with lower limb lymphedema post-gynecologic cancer surgery were chosen. They were split into a control group (n = 30) and a treatment group (n = 30). The control group underwent complex decongestive therapy (CDT) for managing lower limb lymphedema after gynecologic cancer surgery, while the treatment group received diaphragmatic breathing combined with limb coordination training alongside CDT. Both groups completed a 4-week treatment regimen. The lower limb lymphedema symptoms were evaluated using the genital, lower limb, buttock, and abdomen (GCLQ) scores; bilateral lower limb circumference measurements; and anxiety and depression scores. Results: Compared to sole CDT administration, individuals undergoing diaphragmatic breathing coupled with limb coordination training experienced notable reductions in scores for the self-perceived symptom assessment questionnaire (GCLQ), bilateral lower limb circumference, as well as anxiety and depression scores. Conclusion: The incorporation of diaphragmatic breathing combined withalongside limb coordination training can accelerate and augment the efficacy of treating lower limb lymphedema post-gynecologic cancer surgery.

Effectiveness of Lianhua Qingwen Granule and Jingyin Gubiao Prescription in Omicron BA.2 Infection and Hospitalization: A Real-World Study of 56,244 Cases in Shanghai, China.

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (CT) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS: Patients with a nadir CT value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.

ERß activation improves nonylphenol-induced depression and neurotransmitter secretion disruption via the TPH2/5-HT pathway.

The aim of this study is to investigate the role of estrogen receptor ß (ERß) in nonylphenol (NP) - induced depression - like behavior in rats and its impact on the regulation of the TPH2/5-HT pathway. In the in vitro experiment, rat basophilic leukaemia cells (RBL-2H3) cells were divided into the four groups: blank group, NP group (20 µM), ERß agonist group (0.01 µM), and NP＋ERß agonist group (20 µM＋0.01 µM). For the in vivo experiment, 72 adult male Sprague-Dawley rats were randomly divided into following six groups: the Control, NP (40 mg/kg) group, ERß agonist (2 mg/kg, Diarylpropionitrile (DPN)) group, ERß inhibitor (0.1 mg/kg, 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl) phenol (PHTPP)) group, NP+ERß agonist (40 mg/kg NP ＋ 2 mg/kg DPN) group, and NP+ERß inhibitor (40 mg/kg NP + 0.1 mg/kg PHTPP) group, with 12 rats in each group. Each rat in drug group were given NP by gavage and/or received a single intraperitoneal injection of DPN 2 mg/kg or PHTPP 0.1 mg/kg. Both in vivo and in vitro, NP group showed a decrease in the expression levels of ERß, tryptophan hydroxylase (TPH1), and tryptophan hydroxylase-2 (TPH2) genes and proteins, and reduced levels of DA, NE, and 5-hydroxytryptophan (5-HT) neurotransmitters. RBL-2H3 cells showed signs of cell shrinkage, with rounded cells, increased suspension and more loosely arranged cells. The effectiveness of the ERß agonist stimulation exhibited an increase exceeding 60% in RBL-2H3 cells. The application of ERß agonist resulted in an alleviation the aforementioned alterations. ERß agonist activated the TPH2/5-HT signaling pathways. Compared to the control group, the NP content in the brain tissue of the NP group was significantly increased. The latency to eat for the rats was longer and the amount of food consumed was lower, and the rats had prolonged immobility time in the behavioral experiment of rats. The expression levels of ERß, TPH1, TPH2, 5-HT and 5-HITT proteins were decreased in the NP group, suggesting NP-induced depression-like behaviours as well as disturbances in the secretion of serum hormones and monoamine neurotransmitters. In the NP group, the midline raphe nucleus showed an elongated nucleus with a dark purplish-blue colour, nuclear atrophy, displacement and pale cytoplasm. ERß might ameliorate NP-induced depression-like behaviors, and secretion disorders of serum hormones and monoamine neurotransmitters via activating TPH2/5-HT signaling pathways.

Squamous cell carcinoma of ear and temporal bone: A retrospective study on clinicopathological predictors.

BACKGROUND: Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China. METHODS: A cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index. RESULTS: Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval [CI] = 39-64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model. CONCLUSION: We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients.

Feasibility Study on Constructing Dosimetric Correlated Geometric Parameters for Automatic Segmentation Evaluation.

PURPOSE: To investigate the feasibility of constructing new geometric parameters that correlate well with dosimetric parameters. METHODS: 100 rectal cancer patients were enrolled. The targets were identified manually, while the organs at risk (bladder, small bowel, left and right femoral heads) were segmented both manually and automatically. The radiotherapy plans were optimized according to the automatically contoured organs at risk. Forty cases were randomly selected to establish the relationship between dose and distance for each organ at risk, termed "dose-distance curves," which were then applied to the new geometric parameters. The correlation between these new geometric parameters and dosimetric parameters was analyzed in the remaining 60 test cases. RESULTS: The "dose-distance curves" were similar across the four organs at risk, exhibiting an inverse function shape with a rapid decrease initially and a slower rate at a later stage. The Pearson correlation coefficients of new geometric parameters and dosimetric parameters in the bladder, small intestine, and left and right femur heads were 0.96, 0.97, 0.88, and 0.70, respectively. CONCLUSIONS: The new geometric parameters predicated on "distance from the target" showed a high correlation with corresponding dosimetric parameters in rectal cancer cases. It is feasible to utilize the new geometric parameters to evaluate the dose deviation attributable to automatic segmentation.

Protective effect of rubber seed oil on human endothelial cells.

OBJECTIVE: This study was conducted to characterize the antioxidant and anti-inflammatory properties of Rubber Seed Oil (RSO) against atherosclerosis (AS) through the study of the protective effects and mechanisms on human umbilical vein endothelial cells (HUVECs) injury induced by oxidized low-density lipoprotein (ox-LDL). METHODS: HUVECs were treated with RSO, ox-LDL, RSO + ox-LDL, respectively, followed by cell activity testing, levels of IL-1ß, IL-6, IL-10, TNF-α, ROS, NO, the mRNA expression of eNOS and protein expression of MCP-1, VCAM-1, eNOS, TLR4, NF-κB p65、p-NF-κB p65. RESULTS: Compared with the ox-LDL group, cell viability, NO level and the expression of eNOS mRNA significantly increased. and the levels of pro-inflammatory factors such as IL-1ß, IL-6, TNF-α, IL-10, ROS were significantly decreased, which was accompanied by decreases in TLR4 mRNA, TLR4, MCP-1, VCAM-1 protein expression, as well as the ratio of NF-κB p-p65/p65 in the group treated with 250 µg/ml ox-LDL + 50 µg/ml RSO, 250 µg/ml ox-LDL + 100 µg/ml RSO, 250 µg/ml ox-LDL + 150 µg/ml RSO. CONCLUSIONS: RSO can reduce the expression of pro-inflammatory mediators, oxidative factors involved in injured vascular endothelial cells, exhibiting anti-inflammatory and antioxidant properties HUVECs exposed to ox-LDL. In addition, it may alleviate endothelial cell damage by inhibiting the TLR4/NF-κB signaling pathway.

Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay.

The yeast Saccharomyces cerevisiae and most eukaryotes carry two 5' → 3' exoribonuclease paralogs. In yeast, they are called Xrn1, which shuttles between the nucleus and the cytoplasm, and executes major cytoplasmic messenger RNA (mRNA) decay, and Rat1, which carries a strong nuclear localization sequence (NLS) and localizes to the nucleus. Xrn1 is 30% identical to Rat1 but has an extra ~500 amino acids C-terminal extension. In the cytoplasm, Xrn1 can degrade decapped mRNAs during the last round of translation by ribosomes, a process referred to as "cotranslational mRNA decay." The division of labor between the two enzymes is still enigmatic and serves as a paradigm for the subfunctionalization of many other paralogs. Here we show that Rat1 is capable of functioning in cytoplasmic mRNA decay, provided that Rat1 remains cytoplasmic due to its NLS disruption (cRat1). This indicates that the physical segregation of the two paralogs plays roles in their specific functions. However, reversing segregation is not sufficient to fully complement the Xrn1 function. Specifically, cRat1 can partially restore the cell volume, mRNA stability, the proliferation rate, and 5' → 3' decay alterations that characterize xrn1Δ cells. Nevertheless, cotranslational decay is only slightly complemented by cRat1. The use of the AlphaFold prediction for cRat1 and its subsequent docking with the ribosome complex and the sequence conservation between cRat1 and Xrn1 suggest that the tight interaction with the ribosome observed for Xrn1 is not maintained in cRat1. Adding the Xrn1 C-terminal domain to Rat1 does not improve phenotypes, which indicates that lack of the C-terminal is not responsible for partial complementation. Overall, during evolution, it appears that the two paralogs have acquired specific characteristics to make functional partitioning beneficial.

Description of a pathogenic strain of Aeromonas dhakensis isolated from Ancherythroculter nigrocauda in an inland region of China.

Aeromonas dhakensis is reported as an emerging pathogenic species within the genus Aeromonas and is widely distributed in tropical coastal areas. This study provided a detailed description and characterization of a strain of A. dhakensis (202108B1) isolated from diseased Ancherythroculter nigrocauda in an inland region of China. Biochemical tests identified the isolate at the genus level, and the further molecular analysis of concatenated housekeeping gene sequences revealed that the strain belonged to the species A. dhakensis. The isolated A. dhakensis strain was resistant to five antibiotics, namely, penicillin, ampicillin, clindamycin, cephalexin, and imipenem, while it was susceptible to or showed intermediate resistance to most of the other 15 tested antibiotics. The isolated strain of A. dhakensis caused acute hemorrhagic septicemia and tissue damage in artificially infected A. nigrocauda, with a median lethal dose of 7.76 × 104 CFU/fish. The genome size of strain 202108B1 was 5 043 286 bp, including 1 chromosome and 4 plasmids. This is the first detailed report of the occurrence of infection caused by an A. dhakensis strain causing infection in an aquaculture system in inland China, providing important epidemiological data on this potential pathogenic species.

Decoding glycosylation potential from protein structure across human glycoproteins with a multi-view recurrent neural network.

Glycosylation is described as a non-templated biosynthesis. Yet, the template-free premise is antithetical to the observation that different N-glycans are consistently placed at specific sites. It has been proposed that glycosite-proximal protein structures could constrain glycosylation and explain the observed microheterogeneity. Using site-specific glycosylation data, we trained a hybrid neural network to parse glycosites (recurrent neural network) and match them to feasible N-glycosylation events (graph neural network). From glycosite-flanking sequences, the algorithm predicts most human N-glycosylation events documented in the GlyConnect database and proposed structures corresponding to observed monosaccharide composition of the glycans at these sites. The algorithm also recapitulated glycosylation in Enhanced Aromatic Sequons, SARS-CoV-2 spike, and IgG3 variants, thus demonstrating the ability of the algorithm to predict both glycan structure and abundance. Thus, protein structure constrains glycosylation, and the neural network enables predictive in silico glycosylation of uncharacterized or novel protein sequences and genetic variants.

Cortical structure reorganization and correlation with attention deficit in subcortical stroke: An underlying pattern analysis.

BACKGROUND: Subcortical stroke may significantly alter the cerebral cortical structure and affect attention function, but the details of this process remain unclear. The study aimed to investigate the neural substrates underlying attention impairment in patients with subcortical stroke. MATERIALS AND METHODS: In this prospective observational study, two distinct datasets were acquired to identify imaging biomarkers underlying attention deficit. The first dataset consisted of 86 patients with subcortical stroke, providing a cross-sectional perspective, whereas the second comprised 108 patients with stroke, offering longitudinal insights. All statistical analyses were subjected to false discovery rate correction upon P < 0.05. RESULTS: In the chronic-stage data, the stroke group exhibited significantly poorer attention function compared with that of the control group. The cortical structure analysis showed that patients with stroke exhibited decreased cortical thickness of the precentral gyrus and surface area of the cuneus, along with an increase in various frontal, occipital, and parietal cortices regions. The declined attention function positively correlated with the superior frontal gyrus cortical thickness and supramarginal gyrus surface area. In the longitudinal dataset, patients with stroke showed gradually increasing cortical thickness and surface area within regions of obvious structural reorganization. Furthermore, deficient attention positively correlated with supramarginal gyrus surface area both at the subacute and chronic stages post-stroke. CONCLUSIONS: Subcortical stroke can elicit dynamic reorganization of cortical areas associated with attention impairment. Moreover, the altered surface area of the supramarginal gyrus is a potential neuroimaging biomarker for attention deficits.

The EPRS-ATF4-COLI pathway axis is a potential target for anaplastic thyroid carcinoma therapy.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is recognized as the most aggressive and malignant form of thyroid cancer, underscoring the critical need for effective therapeutic strategies to curb its progression and improve patient prognosis. Halofuginone (HF), a derivative of febrifugine, has displayed antitumor properties across various cancer types. However, there is a paucity of published research focused on the potential of HF to enhance the clinical efficacy of treating ATC. OBJECTIVE: In this study, we thoroughly investigated the antitumor effects and mechanisms of HF in ATC, aiming to discover lead compounds for treating ATC and reveal novel therapeutic targets for ATC tumors. METHODS: A series of assays, including CCK8, colony formation, tumor xenograft models, and ATC tumor organoid experiments, were conducted to evaluate the anticancer properties of HF both in vitro and in vivo. Techniques such as drug affinity responsive target stability (DARTS), western blot, immunofluorescence, and immunohistochemistry were employed to pinpoint HF target proteins within ATC. Furthermore, we harnessed the GEPIA and GEO databases and performed immunohistochemistry to validate the therapeutic potential of the glutamyl-prolyl-tRNA-synthetase (EPRS)- activating transcription factor 4 (ATF4)- type I collagen (COLI) pathway axis in the context of ATC. The study also incorporated RNA sequencing analysis, confocal imaging, and flow cytometry to delve into the molecular mechanisms of HF in ATC. RESULTS: HF exhibited a substantial inhibitory impact on cell proliferation in vitro and on tumor growth in vivo. The DARTS results highlighted HF's influence on EPRS within ATC cells, triggering an amino acid starvation response (AASR) by suppressing EPRS expression, consequently leading to a reduction in COLI expression in ATC cells. The introduction of proline mitigated the effect of HF on ATF4 and COLI expression, indicating that the EPRS-ATF4-COLI pathway axis was a focal target of HF in ATC. Analysis of the expression levels of the EPRS, ATF4, and COLI proteins in thyroid tumors, along with an examination of the relationship between COLI expression and thyroid tumor stage, revealed that HF significantly inhibited the growth of ATC tumor organoids, demonstrating the therapeutic potential of targeting the EPRS-ATF4-COLI pathway axis in ATC. RNA sequencing analysis revealed significant differences in the pathways associated with metastasis and apoptosis between control and HF-treated cells. Transwell assays and flow cytometry experiments provided evidence of the capacity of HF to impede cell migration and induce apoptosis in ATC cells. Furthermore, HF hindered cell metastasis by suppressing the epithelial-mesenchymal transition (EMT) pathway, acting through the inhibition of FAK-AKT-NF-κB/Wnt-ß-catenin signaling and restraining angiogenesis via the VEGF pathway. HF also promoted apoptosis through the mitochondrial apoptotic pathway. CONCLUSION: This study provided inaugural evidence suggesting that HF could emerge as a promising therapeutic agent for the treatment of ATC. The EPRS-ATF4-COLI pathway axis stood out as a prospective biomarker and therapeutic target for ATC.

Streamlining social media information retrieval for public health research with deep learning.

OBJECTIVE: Social media-based public health research is crucial for epidemic surveillance, but most studies identify relevant corpora with keyword-matching. This study develops a system to streamline the process of curating colloquial medical dictionaries. We demonstrate the pipeline by curating a Unified Medical Language System (UMLS)-colloquial symptom dictionary from COVID-19-related tweets as proof of concept. METHODS: COVID-19-related tweets from February 1, 2020, to April 30, 2022 were used. The pipeline includes three modules: a named entity recognition module to detect symptoms in tweets; an entity normalization module to aggregate detected entities; and a mapping module that iteratively maps entities to Unified Medical Language System concepts. A random 500 entity samples were drawn from the final dictionary for accuracy validation. Additionally, we conducted a symptom frequency distribution analysis to compare our dictionary to a pre-defined lexicon from previous research. RESULTS: We identified 498 480 unique symptom entity expressions from the tweets. Pre-processing reduces the number to 18 226. The final dictionary contains 38 175 unique expressions of symptoms that can be mapped to 966 UMLS concepts (accuracy = 95%). Symptom distribution analysis found that our dictionary detects more symptoms and is effective at identifying psychiatric disorders like anxiety and depression, often missed by pre-defined lexicons. CONCLUSIONS: This study advances public health research by implementing a novel, systematic pipeline for curating symptom lexicons from social media data. The final lexicon's high accuracy, validated by medical professionals, underscores the potential of this methodology to reliably interpret, and categorize vast amounts of unstructured social media data into actionable medical insights across diverse linguistic and regional landscapes.