Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlations of insulin resistance and HbA1c with cytokines IGF-1, bFGF and IL-6 in the aqueous humor of patients with diabetic cataract.

OBJECTIVE The study aimed to investigate the correlations of insulin resistance and hemoglobin A1c (HbA1c) with cytokines [insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF) and interleukin-6 (IL-6)] in the aqueous humor of patients with diabetic cataract. PATIENTS AND METHODS 59 patients with diabetic cataract and 58 patients with simple cataract treated in Jining No. 1 People´s Hospital (Jining, China) from January 2017 to February 2018, were selected randomly. The levels of homeostasis model assessment of insulin resistance (HOMA-IR) and HbAlc, as well as IGF-1, bFGF and IL-6 in the aqueous humor were compared between the two groups. The correlations of HOMA-IR and HbAlc with IGF-1, bFGF and IL-6 were analyzed. In control group, the levels of HOMA-IR and HbAlc, as well as IGF-1, bFGF and IL-6 in the aqueous humor were significantly lower than those in observation group (p<0.05). RESULTS Compared with the group with HbAlc ≤ 7%, the groups with HbAlc ≥ 9% and 7% <HbAlc< 9% had increased relevant indexes. HbAlc was positively correlated with IGF-1, bFGF and IL-6 (r=0.8309, p<0.001; r=0.8968, p<0.001; r=0.8205, p<0.001). HOMA-IR had positive correlations with IGF-1, bFGF and IL-6 (r=0.9091, p<0.001; r=0.9605, p<0.001; r=0.8118, p<0.001). IGF-1 was positively related to bFGF and IL-6 (r=0.9475, p<0.001; r=0.9112, p<0.001). CONCLUSIONS For patients with diabetic cataract, HOMA-IR and HbAlc were associated with IGF-1, bFGF and IL-6 in the aqueous humor. The measurement of those indexes can help to judge the disease conditions accurately, having good predictive value.
Inhibition of polarity-regulating kinase PAR1b contributes to Helicobacter pylori inflicted DNA Double Strand Breaks in gastric cells

ABSTRACT The serine/threonine kinase Par1 is a core component of the machinery that sets up polarity in the embryo and regulates cell fate decisions but its role in the homeostasis of adult tissues is poorly understood. Inhibition of Par1 by the bacterium Helicobacter pylori (H. pylori) represents the only established pathology that affects Par1 function in an adult epithelium. Thus, during chronic H. pylori infection of the gastric mucosa Par1 is one of the targets of the non-obligate H.pylori cytotoxic protein and oncogene CagA, which stimulates inflammation and triggers morphological changes, both believed to contribute to the gastric cancer risk imposed by H. pylori infection. Based on Par1’s role in cell polarity, it has been speculated that Par1 inhibition affects epithelial polarity. Here we report the unexpected finding that CagA-mediated Par1-inhibition promotes the generation of DNA Double Strand Breaks in primary gastric epithelial cells, which likely contributes to the reported accumulation of mutations in chronically infected mucosal cells. Abbreviations: AGS: human gastric adenocarcinoma cell line; CM: CagA Multimerization (and Par1 binding) domain; H. pylori: Helicobacter pylori; DSB: Double Strand Break; HGECs: human (primary) gastric epithelial cells; IB: immunoblot; IF: immunofluorescence; MOI: Multiplicity of Infection; ROS: reactive oxygen species; Par1: Partitioning Defective 1 kinase; WT: wild type
Cbs overdosage is necessary and sufficient to induce cognitive phenotypes in mouse models of Down syndrome and interacts genetically with Dyrk1a

Identifying dosage sensitive genes is a key to understand the mechanisms underlying intellectual disability in Down syndrome (DS). The Dp(17Abcg1-Cbs)1Yah DS mouse model (Dp1Yah) show cognitive phenotype and needs to be investigated to identify the main genetic driver. Here, we report that, in the Dp1Yah mice, 3 copies of the Cystathionine-beta-synthase gene (Cbs) are necessary to observe a deficit in the novel object recognition (NOR) paradigm. Moreover, the overexpression of Cbs alone is sufficient to induce NOR deficit. Accordingly targeting the overexpression of human CBS, specifically in Camk2a-expressing neurons, leads to impaired objects discrimination. Altogether this shows that Cbs overdosage is involved in DS learning and memory phenotypes. In order to go further, we identified compounds that interfere with the phenotypical consequence of CBS overdosage in yeast. Pharmacological intervention in the Tg(CBS) with one selected compound restored memory in the novel object recognition. In addition, using a genetic approach, we demonstrated an epistatic interaction between Cbs and Dyrk1a, another human chromosome 21 gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1a and an already known target for DS therapeutic intervention. Further analysis using proteomic approaches highlighted several pathways, including synaptic transmission, cell projection morphogenesis, and actin cytoskeleton, that are affected by DYRK1A and CBS overexpression. Overall we demonstrated that CBS overdosage underpins the DS-related recognition memory deficit and that both CBS and DYRK1A interact to control accurate memory processes in DS. In addition, our study establishes CBS as an intervention point for treating intellectual deficiencies linked to DS. SIGNIFICANT STATEMENT Here, we investigated a region homologous to Hsa21 and located on mouse chromosome 17. We demonstrated using three independent genetic approaches that the overdosage of the Cystathionine-beta-synthase gene (Cbs) gene, encoded in the segment, is necessary and sufficient to induce deficit in novel object recognition (NR). In addition, we identified compounds that interfere with the phenotypical consequence of CBS overdosage in yeast and in mouse transgenic lines. Then we analyzed the relation between Cbs overdosage and the consequence of DYRK1a overexpression, a main driver of another region homologous to Hsa21 and we demonstrated that an epistatic interaction exist between Cbs and Dyrk1a affecting different pathways, including synaptic transmission, cell projection morphogenesis, and actin cytoskeleton.
Random Forest Analysis of Untargeted Metabolomics Data Suggests Increased Use of Omega Fatty Acid Oxidation Pathway in Drosophila Melanogaster Larvae Fed a Medium Chain Fatty Acid Rich High-Fat Diet

Obesity is a complex disease, shaped by both genetic and environmental factors such as diet. In this study, we use untargeted metabolomics and Drosophila melanogaster to model how diet and genotype shape the metabolome of obese phenotypes. We used 16 distinct outbred genotypes of Drosophila larvae raised on normal (ND) and high-fat (HFD) diets, to produce three distinct phenotypic classes; genotypes that stored more triglycerides on a ND relative to the HFD, genotypes that stored more triglycerides on a HFD relative to ND, and genotypes that showed no change in triglyceride storage on either of the two diets. Using untargeted metabolomics we characterized 350 metabolites: 270 with definitive chemical IDs and 80 that were chemically unidentified. Using random forests, we determined metabolites that were important in discriminating between the HFD and ND larvae as well as between the triglyceride phenotypic classes. We found that flies fed on a HFD showed evidence of an increased use of omega fatty acid oxidation pathway, an alternative to the more commonly used beta fatty acid oxidation pathway. Additionally, we observed no correlation between the triglyceride storage phenotype and free fatty acid levels (laurate, caprate, caprylate, caproate), indicating that the distinct metabolic profile of fatty acids in high-fat diet fed Drosophila larvae does not propagate into triglyceride storage differences. However, dipeptides did show moderate differences between the phenotypic classes. We fit Gaussian graphical models (GGMs) of the metabolic profiles for HFD and ND flies to characterize changes in metabolic network structure between the two diets, finding the HFD to have a greater number of edges indicating that metabolome varies more across samples on a HFD. Taken together, these results show that, in the context of obesity, metabolomic profiles under distinct dietary conditions may not be reliable predictors of phenotypic outcomes in a genetically diverse population.
Characterisation and classification of Citri Reticulatae Pericarpium varieties based on UHPLC-Q-TOF-MS/MS combined with multivariate statistical analyses.

INTRODUCTION Citri Reticulatae Pericarpium (CRP), comprising dried pericarps of Citrus reticulata Blanco and its cultivars, is popularly used for its great medicinal and dietary values. Generally, the pericarps from C. reticulate "Chachi" ("Guangchenpi" in Chinese, GCP) is considered to have superior qualities and merit premium price compared with CRP derived from other cultivars (collectively called "Chenpi" in Chinese, CP). Since its multiple origins and derived economic adulteration, it is significant to systematically compare the chemical profiles of different CRP varieties. OBJECTIVE The main objective of this work was to identify the chemical profiles of CRP from different varieties and find out potential chemical markers for differentiating GCP and CP. METHODS In the present study, a total of 42 CRP samples from 10 varieties (including GCP and CP) were analysed by ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) for chemical profiling. Obtained MS/MS data were further employed in multivariate statistical methods to screen the main compounds which contributed to the characterisation and classification of CRP. RESULTS As a result, 73 compounds (mainly flavonoids) were identified or tentatively characterised in these CRP samples. Based on the obtained chemical profiles data, GCP and CP samples could be easily discriminated from each other by statistical analyses. Moreover, seven compounds were selected as having the most discriminating features which contributed to the classification of CRP. CONCLUSION This work obtains a better understanding of the chemical profiles of different CRP varieties and provides a practical strategy for the authentication of GCP and CP.
Association Between Low-Density Lipoprotein Cholesterol Levels and Risk for Sepsis Among Patients Admitted to the Hospital With Infection

Key Points Question What is the association between low levels of low-density lipoprotein cholesterol and risk of sepsis in patients admitted to the hospital with serious infection? Findings In this cohort study of deidentified electronic medical records of patients admitted to the hospital with infection, measured levels of low-density lipoprotein cholesterol in 3961 patients and a low-density lipoprotein cholesterol genetic risk score in 7804 patients were not associated with increased risk of sepsis after adjusting for comorbidities. Meaning Levels of low-density lipoprotein cholesterol are not directly associated with the risk of sepsis or poor outcomes in patients hospitalized with infection.
Effect of Interventional Therapy on IL-1β, IL-6, and Neutrophil-Lymphocyte Ratio (NLR) Levels and Outcomes in Patients with Ischemic Cerebrovascular Disease

Background This study investigated the clinical effect of interventional therapy in ischemic cerebrovascular disease (ICD). Material/Methods A retrospective analysis was performed on 260 ICD patients who were divided into a control group (122 patients, conventional drug treatment) and an observation group (138 patients, interventional therapy plus conventional drug treatment). Enzyme-linked immunosorbent assay was used to examine the expression of IL-1β, IL-6, and NLR. Furthermore, neurological deficit scores and Barthel index scores as well as the correlation of IL-1β, IL-6 and NLR were examined in these 2 groups. Results The expression of IL-1β, IL-6, and NLR significantly decreased in both groups after 1 week or 4 weeks of treatment compared with before treatment (P<0.05). Significant differences in neurological impairment scores were detected between these 2 groups after 4 weeks of treatment (P<0.05), and the control group showed higher neurological deficit scores than did the observation group (P<0.05). Barthel index scores were significantly higher after treatment than before treatment in the control and observation group (P<0.05), and the control group had lower Barthel index scores than did the observation group (P<0.05). Pearson correlation analysis showed that IL-1β, IL-6, and NLR expression were positively correlated in ICD patients (P<0.05). Conclusions Interventional surgery combined with conventional drug therapy can reduce serum IL-1β and IL-6 levels, decrease neurological impairment, and improve the quality of life of patients. The combined treatment group showed better outcomes than did the group that received the drug alone; therefore, combined therapy is suitable for promoting better clinical outcomes.
News about non-secretory exocytosis: mechanisms, properties, and functions

Abstract The fusion by exocytosis of many vesicles to the plasma membrane induces the discharge to the extracellular space of their abundant luminal cargoes. Other exocytic vesicles, however, do not contain cargoes, and thus, their fusion is not followed by secretion. Therefore, two distinct processes of exocytosis exist, one secretory and the other non-secretory. The present review deals with the knowledge of non-secretory exocytosis developed during recent years. Among such developments are the dual generation of the exocytic vesicles, initially released either from the trans-Golgi network or by endocytosis; their traffic with activation of receptors, channels, pumps, and transporters; the identification of their tethering and soluble N-ethylmaleimide-sensitive factor attachment protein receptor complexes that govern membrane fusions; the growth of axons and the membrane repair. Examples of potential relevance of these processes for pathology and medicine are also reported. The developments presented here offer interesting chances for future progress in the field.
Ultrafast Charge Separation in Two-Dimensional CsPbBr3 Perovskite Nanoplatelets.

Two-dimensional (2D) cesium lead halide perovskite colloidal nanoplatelets show sharper excitonic absorption/emission peaks and larger absorption cross section in comparison to bulk materials and quantum dots. It remains unclear how 2D exciton and charge separation properties can be utilized to further enhance the performance of perovskite materials for optoelectrical applications. Herein, we report a study of exciton and interfacial charge-transfer dynamics of CsPbBr3 nanoplatelets via transient absorption spectroscopy. The exciton binding energy (∼260 meV) is determined via detailed spectral analysis. The exciton bleach is caused by band-edge exciton state-filling with negligible single carrier (electron or hole) contributions. Efficient charge separation can be achieved by selective electron and hole transfers to adsorbed molecular acceptors (benzoquinone and phenothiazine, respectively), and the half-life of the charge-separated state (≫100 ns) in nanoplatelet-phenothiazine complexes is >100 fold longer than that in quantum dot-phenothiazine complexes. Our results suggest that CsPbBr3 nanoplatelets are promising materials for photocatalysis and photovoltaic applications.
Posttraumatic Stress Disorder in African American and Latinx Adults: Clinical Course and the Role of Racial and Ethnic Discrimination

Research has suggested that African American and Latinx adults may develop posttraumatic stress disorder (PTSD) at higher rates than White adults, and that the clinical course of PTSD in these minority groups is poor. Factors that may contribute to higher prevalence and poorer outcome in these groups are sociocultural factors and racial stressors, such as experiences with discrimination. To date, however, no research has explored the relationship between experiences with discrimination and risk for PTSD, and very little research has examined the course of illness for PTSD in African American and Latinx samples. The present study examined these variables in the only longitudinal clinical sample of 139 Latinx and 152 African American adults with anxiety disorders, the Harvard/Brown Anxiety Research Project—Phase II. Over 5 years of follow-up, remission rates for African Americans and Latinx adults with PTSD in this sample were 0.35 and 0.15, respectively, and reported frequency of experiences with discrimination significantly predicted PTSD diagnostic status in this sample, but did not predict any other anxiety or mood disorder. These findings demonstrate the chronic course of PTSD in African American and Latinx adults, and highlight the important role that racial and ethnic discrimination may play in the development of PTSD among these populations. Implications for an increased focus on these sociocultural stressors in the assessment and treatment of PTSD in African American and Latinx individuals are discussed.
Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome

Background Numerous preclinical studies have supported the theory that enhanced activation of mGluR5 signaling, due to the absence or reduction of the FMR1 protein, contributes to cognitive and behavioral deficits in patients with fragile X syndrome (FXS). However multiple phase 2 controlled trials in patients with FXS have failed to demonstrate efficacy of compounds that negatively modulate mGluR5, including two phase 2b randomized controlled trials (RCT) of mavoglurant (AFQ056, Novartis Pharma AG), when the primary measures of interest were behavioral ratings. This has cast some doubt onto the translation of the mGluR5 theory from animal models to humans with the disorder. Methods We evaluated social gaze behavior–a key phenotypic feature of the disorder—and sympathetic nervous system influence on pupil size using a previously-validated eye tracking paradigm as a biobehavioral probe, in 57 adolescent or adult patients with FXS at baseline and following three months of blinded treatment with one of three doses of mavoglurant or placebo, within the context of the AFQ056 RCTs. Results Patients with FXS treated with mavoglurant demonstrated increased total absolute looking time and number of fixations to the eye region while viewing human faces relative to baseline, and compared to those treated with placebo. In addition, patients had greater pupil reactivity to faces relative to baseline following mavoglurant treatment compared to placebo. Discussion The study shows that negative modulation of mGluR5 activity improves eye gaze behavior and alters sympathetically-driven reactivity to faces in patients with FXS, providing preliminary evidence of this drug’s impact on behavior in humans with the disorder.
Mohs micrographic surgery versus wide local excision for melanoma in situ: analysis of a nationwide database

With the rising incidence of melanoma in situ (MIS) or cutaneous melanoma, there is an increasing emphasis on the need to understand optimal treatment strategies. The current standard of surgical care is wide local excision (WLE). Alternative surgical techniques have been proposed including Mohs micrographic surgery (MMS). We aimed to compare survival rates following WLE versus MMS surgery for MIS.
Serum 25-hydroxyvitamin D fluctuations in military personnel during 6-month summer operational deployments in Afghanistan

Abstract Soldier operational performance is determined by their fitness, nutritional status, quality of rest/recovery, and remaining injury/illness free. Understanding large fluctuations in nutritional status during operations is critical to safeguarding health and well-being. There are limited data world-wide describing the effect of extreme climate change on nutrient profiles. This study investigated the effect of hot-dry deployments on vitamin D status (assessed from 25-hydroxyvitamin D (25(OH)D) concentration) of young, male, military volunteers. Two data sets are presented (pilot study, n 37; main study, n 98), examining serum 25(OH)D concentrations before and during 6-month summer operational deployments to Afghanistan (March to October/November). Body mass, percentage of body fat, dietary intake and serum 25(OH)D concentrations were measured. In addition, parathyroid hormone (PTH), adjusted Ca and albumin concentrations were measured in the main study to better understand 25(OH)D fluctuations. Body mass and fat mass (FM) losses were greater for early (pre- to mid-) deployment compared with late (mid- to post-) deployment (P<0·05). Dietary intake was well-maintained despite high rates of energy expenditure. A pronounced increase in 25(OH)D was observed between pre- (March) and mid-deployment (June) (pilot study: 51 (sd 20) v. 212 (sd 85) nmol/l, P<0·05; main study: 55 (sd 22) v. 167 (sd 71) nmol/l, P<0·05) and remained elevated post-deployment (October/November). In contrast, PTH was highest pre-deployment, decreasing thereafter (main study: 4·45 (sd 2·20) v. 3·79 (sd 1·50) pmol/l, P<0·05). The typical seasonal cycling of vitamin D appeared exaggerated in this active male population undertaking an arduous summer deployment. Further research is warranted, where such large seasonal vitamin D fluctuations may be detrimental to bone health in the longer-term.
ParST is a widespread toxin–antitoxin module that targets nucleotide metabolism

Significance Toxin–antitoxin (TA) systems are pairs of genes found throughout bacteria that function in DNA maintenance and bacterial survival. The toxins in these systems function by inactivating critical cell processes like protein synthesis. This work describes a TA system found in 17% of all sequenced bacteria. A high-resolution crystal structure and an array of biochemical tests revealed that this toxin targets an essential enzyme in nucleotide biosynthesis, a unique way in which TA systems can halt bacterial growth. Toxin–antitoxin (TA) systems interfere with essential cellular processes and are implicated in bacterial lifestyle adaptations such as persistence and the biofilm formation. Here, we present structural, biochemical, and functional data on an uncharacterized TA system, the COG5654–COG5642 pair. Bioinformatic analysis showed that this TA pair is found in 2,942 of the 16,286 distinct bacterial species in the RefSeq database. We solved a structure of the toxin bound to a fragment of the antitoxin to 1.50 Å. This structure suggested that the toxin is a mono-ADP-ribosyltransferase (mART). The toxin specifically modifies phosphoribosyl pyrophosphate synthetase (Prs), an essential enzyme in nucleotide biosynthesis conserved in all organisms. We propose renaming the toxin ParT for Prs ADP-ribosylating toxin and ParS for the cognate antitoxin. ParT is a unique example of an intracellular protein mART in bacteria and is the smallest known mART. This work demonstrates that TA systems can induce bacteriostasis through interference with nucleotide biosynthesis.