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Predicting major amputation risk in diabetic foot ulcers using comparative machine learning models for enhanced clinical decision-making

Kerr non-linearity enhances the response of a graphene Josephson bolometer

Resveratrol aggravated H2O2-induced the HK-2 cell damage by inhibiting AKT phosphorylation

Aims Reactive oxygen species (ROS) can induce renal damage when renal ischemia-reperfusion occurs as a result of factors such as renal transplant and shock. It is well established that oxidant damage plays an important role in the mechanism of ischemia-reperfusion. Resveratrol (RSV) is known for its antioxidant properties. However, in our investigations we found that RSV could aggravate human proximal tubular cells (HK-2 cells) damage when exposed to H2O2. Consequently, our findings suggested that RSV may potentially aggravate renal damage in the context of renal ischemia-reperfusion. Methods CCK-8 reagent kits were utilized to assess cell proliferation. Western blot analysis was employed to determine the expression level of protein about γ-H2ax, PTEN, AKT, P-AKT and Cleave-caspase3. Additionally, the process of apoptosis was examined using flow cytometry. Result The CCK-8 assays results revealed a dose-dependent inhibition of cell proliferation when HK-2 cells were exposed to varying concentrations of H2O2. Furthermore, when HK-2 cells were cultured with 250uM H2O2 and different concentrations of RSV, the CCK-8 results indicated a significant reduction in HK-2 cell viability with increasing RSV dosage. Flow cytometry analysis of HK-2 cells exposed to 250uM H2O2 and 10uM RSV demonstrated that RSV exacerbated apoptosis in H2O2-induced HK-2 cells. Western blot analysis revealed that RSV inhibited the expression of P-AKT and exacerbated damage to H2O2-induced HK-2 cells. Subsequently, we selected 10uM MK for further investigation, with CCK-8 results showed a significant reduction in HK-2 cell viability when the AKT phosphorylation process was inhibited by MK. Western blot analysis indicated that the cleave-caspase-3 was further activated when the AKT phosphorylation process was inhibited by MK. Flow cytometry demonstrated a significant increase in the apoptosis of HK-2 cells when the AKT phosphorylation process was inhibited by MK. In the case of P-AKT overexpression, Western blot analysis showed a significant increase in P-AKT expression, while a significant decrease in cleave-caspase-3. Flow cytometry revealed a significant decrease in the apoptosis of HK-2 cells. Finally, Western blot analysis demonstrated a decrease in P-AKT levels along with the expression of PTEN. Conclusions Our research substantiated that RSV could aggravate H2O2 induced HK-2 cells damage by upregulating the expression of PTEN and inhibiting AKT phosphorylation. It suggested that RSV may deteriorate renal damage in the context of renal ischemia-reperfusion injury.

How getting tenure changes researchers’ publication habits — and citations

Disentangling extracellular current of electroactive bacteria with oblique-incidence reflection difference imaging

Spatiotemporal patterns of water and vegetation in Poyang Lake from 2013 to 2021 using remote sensing data

Continuous monitoring and research on Poyang Lake is essential to understand its ecological dynamics and promote sustainable development. Spatial and temporal dynamic monitoring and analyses of vegetation changes in the water body of Poyang Lake are still limited. This study fills this gap by using remote sensing and GIS techniques for dynamic monitoring and analysing the changes of water bodies and vegetation in Poyang Lake from 2013 to 2021. We used a combination of Maximum Likelihood Classification (MLC) and Support Vector Machine (SVM) to preprocess and classify 42 Landsat 8 OLI images. The results showed that the stability of the water body and vegetation varied greatly, with the water body showing the obvious change pattern of water rises, vegetation recedes and water recedes, vegetation grows, and the high-frequency inundation area was concentrated in the northeastern part of the lake (accounting for 60% of the total inundation area). Vegetation frequency distribution showed a pattern of sparse in the north and dense in the south, with the middle frequency area being the most, accounting for 19.88%, and the low frequency area being the least, accounting for 16.09%. The results show that the spatial and temporal distribution characteristics of water body and vegetation in Poyang Lake show low stability, which is a highly dynamic ecosystem. This study relatively makes up for the missing analysis of the stability change of water body and vegetation in the cycle of Poyang Lake, and provides a solid scientific basis for the protection and sustainable management work.

Health risks and genetic architecture of objectively measured multidimensional sleep health

Factors affecting quality of life in connective tissue disease-related interstitial lung disease

Background Connective tissue disease-related interstitial lung disease (CTD-ILD) results in an unrelenting symptom burden and may progress to death. The morbidity and mortality associated with CTD-ILD likely has a profound impact on individuals’ health-related quality of life (HRQOL). The factors associated with HRQOL in other chronic lung diseases have been described, but because of the different clinical and demographic characteristics of CTD-ILD, it is unknown if these same factors are associated with HRQOL in CTD-ILD. Research questions What is the association between patient demographic and disease characteristics, symptoms, and HRQOL in CTD-ILD? Study design and methods A cross-sectional design was used to describe HRQOL in CTD-ILD utilizing a secondary data analysis from the Pulmonary Fibrosis Foundation Patient Registry (PFFPR). Data extracted included demographic (age, gender, and race) and disease characteristics [type of CTD-ILD, duration of disease, forced vital capacity (FVC), supplemental oxygen, immunosuppressant medication use, and pulmonary rehabilitation]. Questionnaires were used to evaluate HRQOL and symptoms of shortness of breath, cough, and fatigue. Results The majority of participants were female (66%), white (78%), had a disease duration of 1–3 years (30%), had scleroderma (25%). The average age was 61 years and FVC of 67% predicted. The majority of participants were not on supplemental oxygen (62%), taking immunosuppressive medications (66%), or active in pulmonary rehabilitation (89%). Female gender, lower FVC, supplemental oxygen use, pulmonary rehabilitation participation, shortness of breath, cough, and fatigue were all correlated with poorer HRQOL. Shortness of breath mediated the relationships between HRQOL and the factors of gender, FVC, supplemental oxygen use, and pulmonary rehabilitation. Fatigue mediated the relationship between HRQOL and pulmonary rehabilitation. Interpretation Disease severity, symptom burden, gender, and disease treatments are associated with poor HRQOL. Recognition of these factors, treating symptoms, and consideration of palliative care may impact HRQOL in CTD-ILD.

Fully exposed Ptn cluster catalysts enable cascade oxidation of polyol to dicarboxylic acid

A computational Evo-Devo approach for elucidating the roles of PLETHORA transcription factors in regulating root development

PLETHORA (PLT) transcription factors play essential roles in regulating various developmental processes in plants, including embryogenesis, rhizotaxis, phyllotaxis, and most prominently, root development, by regulating cell proliferation and differentiation along the root. Despite their important roles in plant development, PLT transcription factors have mainly been studied in Arabidopsis thaliana and only a few crop species. A. thaliana has six PLT genes, which are expressed in overlapping domains and have partially redundant activities, with numerous shared target genes. Here we identified putative PLT orthologs across Viridiplantae, including representatives of all extant plant clades, reconstructing the molecular phylogeny of PLTs and integrating synteny and microsynteny analyses. We suggest that PLTs arose by neofunctionalization prior to the divergence of Spermatophyta and that they might regulate their target genes in a context-specific manner given the presence of intrinsically disordered regions at their N- and C-termini. After identifying direct PLT targets in public databases, we inferred a gene regulatory network driven by PLTs in the root apical meristem in six angiosperm species. Our results suggest that the direct PLT targets regulate ribosome and ribonucleoprotein biogenesis as well as RNA processing, among other basic cellular processes. The central relevance of these processes may account for the high conservation and stability of PLT-driven gene regulatory networks across angiosperms.

China is boosting its Antarctic research. What does that mean for the world?

A diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas

Prioritizing the bottom line over people in a crisis: How leader behavior affects employee psychological distress under economic threat

Aim This study examines the impact of direct supervisors’ leadership on employee psychological distress during crises. Specifically, it explores the relationship between people-oriented and bottom-line-mentality informed leader behaviors and employee psychological distress. The study further hypothesizes that employees’ sense of control functions as a psychological mechanism in this relationship and that this indirect effect is moderated by personal and national economic threat, both of which are particularly salient during crises. Method A quantitative survey was conducted in three waves among 854 employees across Europe (Germany, Italy, the Netherlands and Spain) during the COVID-19 pandemic, a highly salient global crisis. Results Findings indicate that employees with people-oriented leaders report lower psychological distress, mediated by an enhanced sense of control. In contrast, bottom-line-mentality informed leadership is associated with a diminished sense of control, and further with greater psychological distress. These effects are exacerbated under higher personal and national economic threat. Conclusion This study advances understanding of how constructive and destructive leadership behaviors influence employees’ psychological well-being during crises, particularly under economic strain. The findings provide actionable insights for leaders, organizations, and policymakers on mitigating employee psychological distress through leadership strategies that foster a sense of control.

Insights into a water-mediated catalytic triad architecture in CE20 carbohydrate esterases

Abstract Carbohydrate esterases modify polysaccharides by removing different ester moieties thereby affecting their physicochemical properties and their accessibility by glycoside hydrolases. We determined the full-length structures of two members (Fl8CE20_II and PpCE20_II) from the carbohydrate esterase family 20 (CE20) by X-ray crystallography that feature an ancillary domain, inserted into the catalytic SGNH-hydrolase domain. Detailed structural analysis identifies a so far undescribed catalytic triad architecture which lacks the typical aspartate for polarization of the histidine but instead reveals a precisely coordinated water molecule mediating contact between the His and Asp. This coordinated water in the Ser-His-(H2O-Asp/Asn) motif, as further confirmed by mutational studies and by determination of kinetic constants, is crucial for catalytic activity. We therefore term this active site architecture a water-mediated catalytic triad.

Characterization of a Drosophila model to study functions of guarana seeds

The seeds of the Amazonian fruit, guarana (Paullinia cupana), have been used as traditional medicine and, in recent years, as an ingredient in commercial energy beverages. However, mechanisms underlying the beneficial effects of guarana are not well understood. To establish a model system to study molecular mechanisms underlying the beneficial effects of guarana, we investigated how its ingestion affects physiology in the fruit fly, Drosophila melanogaster. We found that guarana enhanced oxidative stress resistance, longevity, physical activity, and fecundity of flies. To deepen our understanding of guarana function, we performed transcriptomic, metabolomic, and fecal microbiome analyses. Transcriptomic analysis identified 58 upregulated and eight downregulated genes in guarana-fed flies. Highly upregulated genes included those encoding detoxification enzymes, such as cytochromes P450 (CYPs), glutathione S-transferases (GSTs), and Juvenile hormone epoxide hydrolase 1 (Jheh1). Metabolomic analysis identified glutathione metabolism, an antioxidant system, as being promoted by guarana ingestion. These findings likely represent the molecular basis for enhanced oxidative stress resistance and longevity in guarana-fed flies. We also analyzed fecal microbiota composition and found significant changes: guarana increased the proportion of probiotic Lactobacillus species, some species known to extend longevity. At the same time, it decreased the proportion of Enterococcus faecalis, a species known to reduce longevity. These changes might have contributed to the beneficial effects of dietary guarana. Thus, we demonstrate that guarana exerts beneficial effects in flies and provide fundamental data for further investigation of its biological mechanisms in Drosophila.

vPro-MS enables identification of human-pathogenic viruses from patient samples by untargeted proteomics

Abstract Viral infections are commonly diagnosed by the detection of viral genome fragments or proteins using targeted methods such as PCR and immunoassays. In contrast, metagenomics enables the untargeted identification of viral genomes, expanding its applicability across a broader spectrum. In this study, we introduce proteomics as a complementary approach for the untargeted identification of human-pathogenic viruses from patient samples. The viral proteomics workflow (vPro-MS) is based on an in-silico derived peptide library covering the human virome in UniProtKB (331 viruses, 20,386 genomes, 121,977 peptides). A scoring algorithm (vProID score) is developed to assess the confidence of virus identification from proteomics data (https://github.com/RKI-ZBS/vPro-MS). In combination with diaPASEF-based data acquisition, this workflow enables the analysis of up to 60 samples per day. The specificity is determined to be >99,9% in an analysis of 221 plasma, swab and cell culture samples covering 17 different viruses. The sensitivity of this approach for the detection of SARS-CoV-2 in nasopharyngeal swabs corresponds to a PCR cycle threshold of 27 with comparable quantitative accuracy to metagenomics. vPro-MS enables the integration of untargeted virus identification in large-scale proteomic studies of biofluids such as human plasma to detect previously undiscovered virus infections in patient specimens.

Prenatal developmental toxicity of Urtica simensis essential oil in rat embryos and rat fetuses

Pregnant women inhaled fresh U. simensis steam vapor to fumigate their bodies, and boiled it for tea. However, the safety of this practice during pregnancy has not yet been reported. This study aimed to evaluate the prenatal developmental toxicity of U.simensis essential oil in rat embryos and fetuses. The essential oil was extracted through hydrodistillation from aerial parts of U.simensis. One hundred pregnant rats were randomly assigned to five groups (20 rats per group). Groups I to III were administered oral doses of 250, 500, and 1000 mg/kg of U.simensis essential oil. Groups IV and V were used as pair-fed and ad libitum controls, respectively. The developing embryos and fetuses were retrieved on 12 and 20 days of gestation, respectively. Embryos were evaluated for growth and developmental delays. Fetuses were evaluated for external, skeletal, and visceral abnormalities. Oral doses of 250 and 500 mg/kg of U.simensis essential oil had no observed adverse effects in both rat embryos and rat fetuses. However, somite numbers and morphological scores were significantly decreased in gravid rats treated with 1000 mg/kg of essential oil. Embryonic developments of the caudal neural tube and forebrain were significantly delayed in pregnant dams administered 1000 mg/kg of essential oil. Crown-rump length and fetal weight were significantly decreased in gravid rats given 1000 mg/kg of essential oil. Gravid rats received 1000 mg/kg of essential oil also revealed a significant increase in fetal resorption. In conclusion, high-dose oral administration of U.simensis essential oil revealed detrimental effects in both rat embryos and fetuses. Therefore, pregnant women should be informed the potential risks associated with the nutraceutical use of U.simensis during pregnancy.

A cytokine-based designer enzyme with an abiological multinuclear metal center exhibits intrinsic and extrinsic catalysis

Detecting outbreaks using a spatial latent field

In this paper, we present a method for estimating the infection-rate of a disease as a spatial-temporal field. Our data comprises time-series case-counts of symptomatic patients in various areal units of a region. We extend an epidemiological model, originally designed for a single areal unit, to accommodate multiple units. The field estimation is framed within a Bayesian context, utilizing a parameterized Gaussian random field as a spatial prior. We apply an adaptive Markov chain Monte Carlo method to sample the posterior distribution of the model parameters condition on COVID-19 case-count data from three adjacent counties in New Mexico, USA. Our results suggest that the correlation between epidemiological dynamics in neighboring regions helps regularize estimations in areas with high variance (i.e., poor quality) data. Using the calibrated epidemic model, we forecast the infection-rate over each areal unit and develop a simple anomaly detector to signal new epidemic waves. Our findings show that anomaly detector based on estimated infection-rates outperforms a conventional algorithm that relies solely on case-counts.

A transcription factor ensemble orchestrates bundle sheath expression in rice

Abstract C4 photosynthesis has evolved in over sixty plant lineages and improves photosynthetic efficiency by ~50%. One unifying character of C4 plants is photosynthetic activation of a compartment such as the bundle sheath, but gene regulatory networks controlling this cell type are poorly understood. In Arabidopsis, a bipartite MYC-MYB transcription factor module restricts gene expression to these cells, but in grasses the regulatory logic allowing bundle sheath gene expression has not been defined. Using the global staple and C3 crop rice, we find that the SULFITE REDUCTASE promoter is sufficient for strong bundle sheath expression. This promoter encodes an intricate cis-regulatory logic with multiple activators and repressors acting combinatorially. Within this landscape we identify a distal cis-regulatory module (CRM) activated by an ensemble of transcription factors from the WRKY, G2-like, MYB-related, DOF, IDD and bZIP families. This module is necessary and sufficient to pattern gene expression to the rice bundle sheath. Oligomerisation of the CRM and fusion to core promoters containing Y-patches allow activity to be increased 220-fold. This CRM generates bundle sheath-specific expression in Arabidopsis indicating deep conservation in function between monocotyledons and dicotyledons. In summary, we identify an ancient, short, and tuneable CRM patterning expression to the bundle sheath that we anticipate will be useful for engineering this cell type in various crop species.