Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma

Background: Previous studies have shown that glycosylation of proteins ofen plays an important role in HCC. However, the potential mechanism of glycosylation in HCC has not been described systematically. Methods: We comprehensively evaluated the glycosylation patterns in HCC samples based on 43 glycosylation regulators, and annotated the modification patterns with the enrichment of immune cells and stromal cells. Considering the heterogeneity of HCC patients, the glycosylation score was constructed using single-sample gene set enrichment analysis (ssGSEA). We also explored the drugs that different HCC patients were sensitive to based on glycosylation mode and score. Results: We identified three glycosylation-regulated gene subtypes. By annotating the subtypes, it was found that the glycosylation regulated gene subtypes was highly matched with three immunophenotypes of HCC (immune-inflamed, immune-excluded, and immune-desert), regardless of the characteristics of immune cell infiltration or prognosis. Based on the characteristic genes of glycosylation-regulated gene subtypes, we constructed a glycosylation-related model, and found that glycosylation-related model was highly consistent with the glycosylation regulated gene subtypes. The glycosylation score that evaluates the glycosylation characteristics of a single HCC sample has high prognostic value, and the prognosis of patients with high glycosylation score is significantly worse. Interestingly, we found that the glycosylation score was closely related to tumor node metastasis (TNM) staging. By applying glycosylation-regulated gene subtypes and glycosylation score to explore the sensitivity of different patients to anticancer drugs, it was found that the sensitivity of Thapsigargin, Shikonin, Embelin and Epothilone. B was closely related to the glycosylation mode. Conclusion: This study reveals that the diversity of glycosylation patterns plays an important role in HCC. Therefore, evaluating the glycosylation patterns of patients with HCC will be helpful in identifying the characteristics of immune cell infiltration and selecting accurate treatment methods.
A review on phytochemical and pharmacological facets of tropical ethnomedicinal plants as reformed DPP-IV inhibitors to regulate incretin activity

Type 2 diabetes mellitus is a metabolic disorder resulting from impaired insulin secretion and resistance. Dipeptidyl peptidase (DPP)-IV is an enzyme known to trigger the catalysis of insulinotropic hormones, further abating the endogenous insulin levels and elevating the glucose levels in blood plasma. In the field of drug development, DPP-IV inhibitors have opened up numerous opportunities for leveraging this target to generate compounds as hypoglycemic agents by regulating incretin activity and subsequently decreasing blood glucose levels. However, the practice of synthetic drugs is an apparent choice but poses a great pharmacovigilance issue due to their incessant undesirable effects. The ideology was set to inventively look upon different ethnomedicinal plants for their anti-diabetic properties to address these issues. To date, myriads of phytochemicals are characterized, eliciting an anti-diabetic response by targeting various enzymes and augmenting glucose homeostasis. Antioxidants have played a crucial role in alleviating the symptoms of diabetes by scavenging free radicals or treating the underlying causes of metabolic disorders and reducing free radical formation. Plant-based DPP-IV inhibitors, including alkaloids, phenolic acid, flavonoids, quercetin, and coumarin, also possess antioxidant capabilities, providing anti-diabetic and antioxidative protection. This review article provides a new gateway for exploring the ability of plant-based DPP-IV inhibitors to withstand oxidative stress under pathological conditions related to diabetes and for reforming the strategic role of ethnomedicinal plants as potent DPP-IV inhibitors through the development of polyherbal formulations and nanophytomedicines to regulate incretin activity.
Characterization of polyvalent Escherichia phage Sa157lw for the biocontrol potential of Salmonella Typhimurium and Escherichia coli O157:H7 on contaminated mung bean seeds

Seeds are one of the primary sources of contamination with foodborne pathogens, such as pathogenic Escherichia coli, and various Salmonella serovars, for produce, particularly sprouts. Due to the susceptibility of sprout growth to chemical-based antimicrobials and the rising issue of antimicrobial resistance, developing innovative antimicrobial interventions is an urgent need. Therefore, the objective of this study was to characterize Escherichia phage Sa157lw (or Sa157lw) for the biocontrol potential of Salmonella Typhimurium and E. coli O157:H7 on contaminated mung bean seeds. Phage Sa157lw was subjected to whole-genome sequencing and biological characterization, including morphology, one-step growth curve, and stress stability tests. Later, antimicrobial activity was determined in vitro and upon application on the mung bean seeds artificially contaminated with E. coli O157:H7 or Salmonella Typhimurium. Sa157lw possessed a contractile tail and belonged to the Kuttervirus genus under the Ackermannviridae family, sharing a close evolutionary relationship with E. coli phage ECML-4 and Kuttervirus ViI; however, tail spike genes (ORF_102 and ORF_104) were the primary region of difference. Comparative genomics showed that Sa157lw encoded a cluster of tail spike genes—including ORF_101, ORF_102, and ORF_104—sharing high amino acid similarity with the counterfeits of various Salmonella phages. Additionally, Sa157lw harbored a unique tail fiber (ORF_103), possibly related to the receptors binding of O157 strains. The genomic evidence accounted for the polyvalent effects of Sa157lw against E. coli O157:H7 and various Salmonella serovars (Typhimurium, Enteritidis, Agona, Saintpaul, and Heidelberg). Furthermore, the phage did not contain any virulence, antibiotic-resistant, or lysogenic genes. Sa157lw had a 30-min latent period on both E. coli O157:H7 and Salmonella Typhimurium, with an estimated burst size of 130 and 220 PFU/CFU, respectively, and was stable at a wide range of temperatures (4–60°C) and pH (pH4 to pH10). The phage application demonstrated a strong anti-E. coli O157:H7 and anti-Salmonella Typhimurium effects in 1.1 and 1.8 log reduction on the contaminated mung bean seeds after overnight storage at 22°C. These findings provide valuable insights into the polyvalent Sa157lw as a potential biocontrol agent of Salmonella Typhimurium and E. coli O157:H7 on sprout seeds.
Barcode clonal tracking of tissue-resident immune cells in rhesus macaque highlights distinct clonal distribution pattern of tissue NK cells

Tissue resident (TR) immune cells play important roles in facilitating tissue homeostasis, coordinating immune responses against infections and tumors, and maintaining immunological memory. While studies have shown these cells are distinct phenotypically and functionally from cells found in the peripheral blood (PB), the clonal relationship between these populations across tissues has not been comprehensively studied in primates or humans. We utilized autologous transplantation of rhesus macaque hematopoietic stem and progenitor cells containing high diversity barcodes to track the clonal distribution of T, B, myeloid and natural killer (NK) cell populations across tissues, including liver, spleen, lung, and gastrointestinal (GI) tract, in comparison with PB longitudinally post-transplantation, in particular we focused on NK cells which do not contain endogenous clonal markers and have not been previously studied in this context. T cells demonstrated tissue-specific clonal expansions as expected, both overlapping and distinct from blood T cells. In contrast, B and myeloid cells showed a much more homogeneous clonal pattern across various tissues and the blood. The clonal distribution of TR NK was more heterogenous between individual animals. In some animals, as we have previously reported, we observed large PB clonal expansions in mature CD56-CD16+ NK cells. Notably, we found a separate set of highly expanded PB clones in CD16-CD56- (DN) NK subset that were also contributing to TR NK cells in all tissues examined, both in TR CD56-CD16+ and DN populations but absent in CD56+16- TR NK across all tissues analyzed. Additionally, we observed sets of TR NK clones specific to individual tissues such as lung or GI tract and sets of TR NK clones shared across liver and spleen, distinct from other tissues. Combined with prior functional data that suggests NK memory is restricted to liver or other TR NK cells, these clonally expanded TR NK cells may be of interest for future investigation into NK cell tissue immunological memory, with implications for development of NK based immunotherapies and an understanding of NK memory.
Screening low-methanol and high-aroma produced yeasts for cider fermentation by transcriptive characterization

The commercial active dry yeast strains used for cider production in China are far behind the requirements of the cider industry development in recent decades. In this study, eight yeasts, including Saccharomyces cerevisiae, Schizosaccharomyces pombe, Pichia bruneiensis, and Pichia kudriavzevii, were screened and assessed by growth performance, methanol production, aroma analysis, and their transcriptive characterization. Saccharomyces cerevisiae strains WFC-SC-071 and WFC-SC-072 were identified as promising alternatives for cider production. Strains WFC-SC-071 and WFC-SC-072 showed an excellent growth capacity characterized by 91.6 and 88.8% sugar utilization, respectively. Methanol production by both strains was below 200 mg/L. Key aroma compounds imparting cider appreciably characteristic aroma increased in cider fermented by strains WFC-SC-071 and WFC-SC-072. RT-qPCR analysis suggested that most genes associated with growth capacity, carbohydrate uptake, and aroma production were upregulated in WFC-SC-071 and WFC-SC-072. Overall, two Saccharomyces cerevisiae strains are the optimal starters for cider production to enable the diversification of cider, satisfy the differences in consumer demand, and promote cider industry development.
Carbon monoxide promotes stomatal initiation by regulating the expression of two EPF genes in Arabidopsis cotyledons

The gaseous molecule carbon monoxide (CO) can freely pass through the cell membrane and participate in signal transduction in the cell to regulate physiological activities in plants. Here, we report that CO has a positive regulatory role in stomatal development. Exogenous CO donor CORM-2 [Tricarbonyldichlororuthenium (II) dimer] treatment resulted in an increase of stomatal index (SI) on the abaxial epidermis of cotyledons in wild-type, which can be reversed by the addition of the CO biosynthesis inhibitor ZnPPIX [Protoporphyrin IX zinc (II)]. Consistent with this result, mutation of the CO biosynthesis gene HY1 resulted in a decrease of SI in hy1-100 plants, while overexpression of HY1 led to an increase of SI. Further investigation revealed that CO acts upstream of SPCH and YDA in the stomatal development pathway, since the loss of function mutants spch-1 and yda-2 were insensitive to CORM-2. The expression of EPF2 was inhibited by CORM-2 treatment in wild type and is lower in hy1 than in wild-type plants. In contrast, the expression of STOMAGEN was promoted by CORM-2 treatment and is higher in HY1-overexpression lines. Loss of function mutants of both epf2 and stomagen are insensitive to CORM-2 treatment. These results indicated that CO positively regulates stomatal initiation and distribution by modulating the expression of EPF2 and STOMAGEN.
Stress-induced impairment reveals the stage and features of post-error adaptive adjustment

An increased reaction time often occurs after error responses (post-error slowing, PES). However, the role of top-down regulation in post-error processing remains to be debated. Impairing cognitive control function through acute stress would help to investigate the role and stage of top-down adaptive regulation in post-error processing. Here, we recruited 50 healthy male participants who were randomly assigned to either a stress condition (Trier Social Stress Task, TSST) or a control condition (control version of the TSST). A color-word Stroop task with different response stimulus intervals (RSIs) was used to investigate the effects of acute stress on different stages of post-error processing. The results showed that cortisol, heart rate, perceived stress level, and negative affect were higher in the stress group (n = 24) than in the control group (n = 26), indicating successful stress induction. The accuracy of post-error response in the control group increased with the extension of RSI, and the reaction time decreased. However, the accuracy of 1,200 ms RSI was close to that of 700 ms RSI in the stress group but was significantly lower than that in the control group. The results suggested that acute stress caused the impairment of top-down adaptive regulation after error. Furthermore, our study manifested adaptive adjustment only in the late stages of post-error processing, indicating the phasic and adaptive features of post-error adjustment.
Proposed new prognostic model using the systemic immune-inflammation index for primary central nervous system lymphoma: A prospective-retrospective multicohort analysis

Purpose The systemic immune-inflammation index (SII) has been considered a novel prognostic biomarker in several types of lymphoma. Our aims were to determine the best statistical relationship between pretreatment SII and survival and to combination of SII and the Memorial Sloan Kettering Cancer Center model (MSKCC) to derive the best prognostic mode in primary central nervous system lymphoma (PCNSL). Methods Pretreatment SII and clinical data in 174 newly diagnosed PCNSL patients were included from two retrospective discovery cohorts (n = 128) and one prospective validation cohort (n = 46). A generalized additive model, Kaplan-Meier curve, and Cox analysis were performed. The high risk versus low risk of SII-MSKCC for the PCNSL cutoff point (0–1 vs. 2–4) was determined by the minimum P-value approach. Results The SII showed a U-shaped relationship with the risk of overall survival (OS; P = 0.006). The patients with low SII or high SII had poorer OS and progression-free survival (PFS) than those with median SII. For PFS and OS, SII-MSKCC was a better predictor than MSKCC alone. The area under the receiver operating characteristic curve of the SII-MSKCC score was 0.84 for OS and 0.78 for PFS in the discovery cohorts. The predictive value of the SII-MSKCC score (OS, 0.88; PFS, 0.95) was verified through the validation cohort. Multivariable Cox analysis and Kaplan-Meier curve showed excellent performance for SII-MSKCC, with significant separation of two groups and better performance than MSKCC alone. Conclusions We propose a new prognostic model using SII, age, and Karnofsky score that outperforms MSKCC alone and enables individualized estimates of patient outcome.
Association between remnant cholesterol and arterial stiffness in a Chinese community-based population: A cross-sectional study

Objectives As a surrogate of arterial stiffness, the brachial-ankle pulse wave velocity (baPWV) is a good predictor of incident cardiovascular disease. Remnant cholesterol (RC) is a proven independent risk factor for cardiovascular disease. However, the relationship between RC and baPWV is unknown. The present study was performed to explore this relationship. Design Cross-sectional study. Setting and participants This study involved 8,028 participants of a community-based atherosclerosis cohort from China. Community residents aged ≥40 years were enrolled by responding to detailed research recruitment posters or by phone invitation. The participants comprised 2,938 (36.60%) men, and their mean age was 56.57 ± 9.04 years. Methods and results The baPWV was measured with a standard protocol using the Omron Colin BP-203RPE III device (Omron Healthcare, Kyoto, Japan). RC was calculated as follows: RC = TC – LDL-C – HDL-C. The mean baPWV was 1,646.85 ± 374.11 cm/s. The median RC concentration was 0.56 (0.41–0.74) mmol/L. In the multivariate logistic regression analyses, the concentrations of RC, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) were all positively and independently associated with baPWV. The baPWV was higher in the fourth than first lipid profile quartile. The HDL-C concentration was inversely associated with baPWV. When RC was forced into the model with other lipid profile indices simultaneously, only the RC and TG concentrations remained significantly associated with baPWV. Conclusion Lipids are independently associated with baPWV. The RC and TG concentrations have stronger associations with arterial stiffness than other lipid indices in the Chinese community-based population.
A user-friendly automatic toolbox for hand kinematic analysis, clinical assessment and postural synergies extraction

The clinical assessment of the human hand is typically conducted through questionnaires or tests that include objective (e.g., time) and subjective (e.g., grasp quality) outcome measures. However, there are other important indicators that should be considered to quantify grasp and movement quality in addition to the time needed by a subject to execute a task, and this is essential for human and artificial hands that attempt to replicate the human hand properties. The correct estimation of hand kinematics is fundamental for computing these indicators with high fidelity, and a technical background is typically required to perform this analysis. In addition, to understand human motor control strategies as well as to replicate them on artificial devices, postural synergies were widely explored in recent years. Synergies should be analyzed not only to investigate possible modifications due to musculoskeletal and/or neuromuscular disorders, but also to test biomimetic hands. The aim of this work is to present an open source toolbox to perform all-in-one kinematic analysis and clinical assessment of the hand, as well as to perform postural synergies extraction. In the example provided in this work, the tool takes as input the position of 28 retroreflective markers with a diameter of 6 mm, positioned on specific anatomical landmarks of the hand and recorded with an optoelectronic motion capture system, and automatically performs 1) hand kinematic analysis (i.e., computation of 23 joint angles); 2) clinical assessment, by computing indicators that allow quantifying movement efficiency (Peak Grip Aperture), smoothness (Normalized Dimensionless Jerk Grasp Aperture) and speed (Peak Velocity of Grasp Aperture), planning capabilities (Time to Peak Grip Aperture), spatial posture (Wrist and Finger Joint Angles) and grasp stability (Posture of Hand Finger Joints), and 3) postural synergies extraction and analysis through the Pareto, Scree and Loadings plots. Two examples are described to demonstrate the applicability of the toolbox: the first one aiming at performing a clinical assessment of a volunteer and the second one aiming at extracting and analyzing the volunteer’s postural synergies. The tool allows calculating joint angles with high accuracy (reconstruction errors below 4 mm and 3.2 mm for the fingers and wrist respectively) and automatically performing clinical assessment and postural synergies extraction. Results can be visually inspected, and data can be saved for any desired post processing analysis. Custom-made protocols to extract joint angles, based on different markersets, could be also integrated in the toolbox. The tool can be easily exploitable in clinical contexts, as it does not require any particular technical knowledge to be used, as confirmed by the usability evaluation conducted (perceived usability = 94.2 ± 5.4). In addition, it can be integrated with the SynGrasp toolbox to perform grasp analysis of underactuated virtual hands based on postural synergies.
The mechanism of exercise for pain management in Parkinson’s disease

The research and clinical applications of exercise therapy to the treatment of Parkinson’s disease (PD) are increasing. Pain is among the important symptoms affecting the daily motor function and quality of life of PD patients. This paper reviewed the progress of research on different exercise therapies for the management of pain caused by PD and described the role and mechanism of exercise therapy for pain relief. Aerobic exercise, strength exercise, and mind-body exercise play an effective role in pain management in PD patients. The pain suffered by PD patients is divided into central neuropathic, peripheral neuropathic, and nociceptive pain. Different types of pain may coexist with different mechanistic backgrounds and treatments. The analgesic mechanisms of exercise intervention in PD-induced pain include altered cortical excitability and synaptic plasticity, the attenuation of neuronal apoptosis, and dopaminergic and non-dopaminergic analgesic pathways, as well as the inhibition of oxidative stress. Current studies related to exercise interventions for PD-induced pain suffer from small sample sizes and inadequate research of analgesic mechanisms. The neurophysiological effects of exercise, such as neuroplasticity, attenuation of neuronal apoptosis, and dopaminergic analgesic pathway provide a sound biological mechanism for using exercise in pain management. However, large, well-designed randomized controlled trials with improved methods and reporting are needed to evaluate the long-term efficacy and cost-effectiveness of exercise therapy for PD pain.
The effects of bilateral prostriata lesions on spatial learning and memory in the rat

Area prostriata is the primary limbic structure for rapid response to the visual stimuli in the far peripheral visual field. Recent studies have revealed that the prostriata receives inputs not only from the visual and auditory cortices but also from many structures critical for spatial processing and navigation. To gain insight into the functions of the prostriata in spatial learning and memory the present study examines the effects of bilateral lesions of the prostriata on motor ability, exploratory interest and spatial learning and memory using the open field, elevated plus-maze and Morris water maze tests. Our results show that the spatial learning and memory abilities of the rats with bilateral prostriata lesions are significantly reduced compared to the control and sham groups. In addition, the lesion rats are found to be less interested in space exploration and more anxious while the exercise capacity of the rats is not affected based on the first two behavioral tests. These findings suggest that the prostriata plays important roles in spatial learning and memory and may be involved in anxiety as well.