Miracle-dz/UniFAR-FTUs huggingface dataset:
Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients

Background Surgical resection is often the preferred treatment for non-small cell lung cancer (NSCLC) patients. Predictive biomarkers after surgery can help monitoring and treating patients promptly, so as to improve the clinical outcome. In this study, we evaluated one potential candidate biomarker, the folate receptor-positive circulating tumor cell (FR+CTC), by investigating its prognostic and predictive significance in NSCLC patients who underwent surgery. Methods In this prospective, observational study, we enrolled NSCLC patients who were eligible to receive surgery. Prior to operation, peripheral blood was collected from each patient for an FR+CTC analysis. FR+CTCs were isolated by negative enrichment using immunomagnetic beads to deplete leukocytes and then quantitatively detected by a ligand-targeted polymerase chain reaction (PCR) method. These patients were then given standard care and were actively followed up for seven years. At the end of the follow-up period, the association between the FR+CTC level and the prognosis in these patients was evaluated. Results Overall, preoperative FR+CTC level was not significantly different among NSCLC patients with adenocarcinoma or non-adenocarcinoma subtypes (P = 0.24). However, between patients with low- and high-risk pathological adenocarcinoma subtypes, the preoperative FR+CTC level was significantly different (P = 0.028). Further, patients with lower preoperative FR+CTC level had longer relapse-free survival (RFS) and overall survival (OS) than those with higher preoperative FR+CTC level (RFS: not reached vs. 33.3 months, P = 0.018; OS: not reached vs. 72.0 months, P = 0.13). In a multivariate COX regression analysis, FR+CTC level (HR = 4.10; 95% CI, 1.23–13.64; P=0.022) and pathological stage (HR = 3.16; 95% CI, 1.79–10.14; P = 0.0011) were independent prognostic factors of RFS. Moreover, FR+CTC level together with adenocarcinoma subtypes provided additional information on risk for disease recurrence compared with FR+CTC or adenocarcinoma subtype alone. Conclusion Our study demonstrated that the preoperative FR+CTC level was a potential predictor for the prognosis of NSCLC patients underwent surgery. Further, when preoperative FR+CTC level is considered together with primary tumor proliferation characteristics, its prognostic value supplements that of these conventional pathological features.
Fermented Soybean Meal Replacement in the Diet of Lactating Holstein Dairy Cows: Modulated Rumen Fermentation and Ruminal Microflora

This study was conducted to examine the influences of replacing soybean meal (SBM) with fermented soybean meal (FSBM) in the diet of lactating Holstein cattle on rumen fermentation and ruminal bacterial microbiome. Twenty-four lactating Chinese Holstein dairy cattle were assigned to each of the two treatments in a completely randomized design: the SBM group [the basal total mixed ration (TMR) diet containing 5.77% SBM] and the FSBM group (the experimental TMR diet containing 5.55% FSBM). This trial lasted for 54 days (14 days for adjustment and 40 days for data and sample collection), and samples of rumen liquid were collected on 34 d and 54 d, respectively. The results showed that replacing SBM with FSBM significantly increased the molar percentages of propionate (P < 0.01) and valerate (P < 0.05), but reduced the total volatile fatty acid (TVFA) concentration (P < 0.05), butyrate molar proportion (P < 0.05), and the acetate to propionate ratio (P < 0.01). The copy numbers of total bacteria (P < 0.05), Fibrobacter succinogenes (P < 0.01), Selenomonas ruminantium (P < 0.01), and Prevotella spp. (P < 0.05) in the FSBM group were greater, while the density of Prevotella ruminicola (P < 0.05) was lower than those in the SBM treatment. Additionally, Succiniclasticum ruminis and Saccharofermentans acetigenes were significantly enriched (P < 0.05) in the rumen fluid of FSBM-fed cows, despite the fact that there was no remarkable difference in the Alpha diversity indexes, structure and KEGG pathway abundances of the bacterial community across the two treatments. It could hence be concluded that the substitution of FSBM for SBM modulated rumen fermentation and rumen bacterial microbiota in lactating Holstein dairy cows. Further research is required to elucidate the relevant mechanisms of FSBM, and provide more insights into the application of FSBM in dairy cattle.
PATZ1 (MAZR) Co-occupies Genomic Sites With p53 and Inhibits Liver Cancer Cell Proliferation via Regulating p27

Liver cancer is the third most common cause of cancer death in the world. POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1/MAZR) is a transcription factor associated with various cancers. However, the role of PATZ1 in cancer progression remains controversial largely due to lack of genome-wide studies. Here we report that PATZ1 regulates cell proliferation by directly regulating CDKN1B (p27) in hepatocellular carcinoma cells. Our PATZ1 ChIP-seq and gene expression microarray analyses revealed that PATZ1 is strongly related to cancer signatures and cellular proliferation. We further discovered that PATZ1 depletion led to an increased rate of colony formation, elevated Ki-67 expression and greater S phase entry. Importantly, the increased cancer cell proliferation was accompanied with suppressed expression of the cyclin-dependent kinase inhibitor CDKN1B. Consistently, we found that PATZ1 binds to the genomic loci flanking the transcriptional start site of CDKN1B and positively regulates its transcription. Notably, we demonstrated that PATZ1 is a p53 partner and p53 is essential for CDKN1B regulation. In conclusion, our study provides novel mechanistic insights into the inhibitory role of PATZ1 in liver cancer progression, thereby yielding a promising therapeutic intervention to alleviate tumor burden.
COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception—A Systematic Review

Clinical reports of neurological manifestations associated with severe coronavirus disease 2019 (COVID-19), such as acute ischemic stroke (AIS), encephalopathy, seizures, headaches, acute necrotizing encephalitis, cerebral microbleeds, posterior reversible leukoencephalopathy syndrome, hemophagocytic lymphohistiocytosis, peripheral neuropathy, cranial nerve palsies, transverse myelitis, and demyelinating disorders, are increasing rapidly. However, there are comparatively few studies investigating the potential impact of immunological responses secondary to hypoxia, oxidative stress, and excessive platelet-induced aggregation on the brain. This scoping review has focused on the pathophysiological mechanisms associated with peripheral and consequential neural (central) inflammation leading to COVID-19-related ischemic strokes. It also highlights the common biological processes shared between AIS and COVID-19 infection and the importance of the recognition that severe respiratory dysfunction and neurological impairments associated with COVID and chronic inflammation [post-COVID-19 neurological syndrome (PCNS)] may significantly impact recovery and ability to benefit from neurorehabilitation. This study provides a comprehensive review of the pathobiology of COVID-19 and ischemic stroke. It also affirms that the immunological contribution to the pathophysiology of COVID-19 is predictive of the neurological sequelae particularly ischemic stroke, which makes it the expectation rather than the exception. This work is of fundamental significance to the neurorehabilitation community given the increasing number of COVID-related ischemic strokes, the current limited knowledge regarding the risk of reinfection, and recent reports of a PCNS. It further highlights the need for global collaboration and research into new pathobiology-based neurorehabilitation treatment strategies and more integrated evidence-based care.
Evaluation of Glacial Lake Outburst Flood Susceptibility Using Multi-Criteria Assessment Framework in Mahalangur Himalaya

Ongoing recession of glaciers in the Himalaya in response to global climate change has far-reaching impacts on the formation and expansion of glacial lakes. The subsequent glacial lake outburst floods (GLOFs) are a significant threat to lives and livelihoods as they can cause catastrophic damage up to hundreds of kilometres downstream. Previous studies have reported the rapid expansion of glacial lakes and several notable destructive past GLOF events in the Mahalangur Himalaya, suggesting a necessity of timely and updated GLOF susceptibility assessment. Here, an updated inventory of glacial lakes across the Mahalangur Himalaya is developed based on 10-m Sentinel-2 satellite data from 2018. Additionally, the GLOF susceptibilities of glacial lakes (≥0.045 km2) are evaluated using a multi-criteria-based assessment framework where six key factors are selected and analyzed. Weight for each factor was assigned from the analytical hierarchy process. Glacial lakes are classified into very low, low, medium, high, and very high GLOF susceptibility classes depending upon their susceptibility index based on analysis of three historical GLOF events in the study area. The result shows the existence of 345 glacial lakes (>0.001 km2) with a total area of 18.80 ± 1.35 km2 across the region in 2018. Furthermore, out of the 64 glacial lakes (≥0.045 km2) assessed, seven were identified with very high GLOF susceptibility. We underline that pronounced glacier-lake interaction will likely increase the GLOF susceptibility. Regular monitoring and more detailed fieldworks for these highly susceptible glacial lakes are necessary. This will benefit in early warning and disaster risk reduction of downstream communities.
Antimicrobial Synergy of Silver-Platinum Nanohybrids With Antibiotics

Various bacterial pathogens are responsible for nosocomial infections resulting in critical pathophysiological conditions, mortality, and morbidity. Most of the bacterial infections are associated with biofilm formation, which is resistant to the available antimicrobial drugs. As a result, novel bactericidal agents need to be fabricated, which can effectively combat the biofilm-associated bacterial infections. Herein, for the first time we report the antimicrobial and antibiofilm properties of silver-platinum nanohybrids (AgPtNHs), silver nanoparticles (AgNPs), and platinum nanoparticles (PtNPs) against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The AgPtNHs were synthesized by a green route using Dioscorea bulbifera tuber extract at 100°C for 5 h. The AgPtNHs ranged in size from 20 to 80 nm, with an average of ∼59 nm. AgNPs, PtNPs, and AgPtNHs showed a zeta potential of −14.46, −1.09, and −11.39 mV, respectively. High antimicrobial activity was observed against P. aeruginosa and S. aureus and AgPtNHs exhibited potent antimicrobial synergy in combination with antibiotics such as streptomycin, rifampicin, chloramphenicol, novobiocin, and ampicillin up to variable degrees. Interestingly, AgPtNHs could inhibit bacterial biofilm formation significantly. Hence, co-administration of AgPtNHs and antibiotics may serve as a powerful strategy to treat bacterial infections.
Amphibian Hormones, Calcium Physiology, Bone Weight, and Lung Use Call for a More Inclusive Approach to Understanding Ossification Sequence Evolution

Skeleton plays a huge role in understanding how vertebrate animals have diversified in phylogeny, ecology and behavior. Recent evo-devo research has used ossification sequences to compare skeletal development among major groups, to identify conserved and labile aspects of a sequence within a group, to derive ancestral and modal sequences, and to look for modularity based on embryonic origin and type of bone. However, questions remain about how to detect and order bone appearances, the adaptive significance of ossification sequences and their relationship to adult function, and the utility of categorizing bones by embryonic origin and type. Also, the singular focus on bone appearances and the omission of other tissues and behavioral, ecological and life history events limit the relevance of such analyses. Amphibians accentuate these concerns because of their highly specialized biphasic life histories and the exceptionally late timing, and high variability of their ossification sequences. Amphibians demonstrate a need for a whole-animal, whole-ontogeny approach that integrates the entire ossification process with physiology, behavior and ecology. I discuss evidence and hypotheses for how hormone mediation and calcium physiology might elicit non-adaptive variability in ossification sequence, and for adaptive strategies to partition larval habitats using bone to offset the buoyancy created by lung use. I also argue that understanding plasticity in ossification requires shifting focus away from embryonic development and adult function, and toward postembryonic mechanisms of regulating skeletal growth, especially ones that respond directly to midlife environments and behaviors.
Computational Screening of Doped Graphene Electrodes for Alkaline CO2 Reduction

The electrocatalytic CO2 reduction reaction (CO2RR) is considered as one of the most promising approaches to synthesizing carbonaceous fuels and chemicals without utilizing fossil resources. However, current technologies are still in the early phase focusing primarily on identifying optimal electrode materials and reaction conditions. Doped graphene-based materials are among the best CO2RR electrocatalysts and in the present work we have performed a computational screening study to identify suitable graphene catalysts for CO2RR to CO under alkaline conditions. Several types of modified-graphene frameworks doped with metallic and non-metallic elements were considered. After establishing thermodynamically stable electrodes, the electrochemical CO2RR to CO is studied in the alkaline media. Both concerted proton-coupled electron transfer (PCET) and decoupled proton and electron transfer (ETPT) mechanisms were considered by developing and using a generalization of the computational hydrogen electrode approach. It is established that the CO2 electrosorption and associated charge transfer along the ETPT pathway are of utmost importance and significantly impact the electrochemical thermodynamics of CO2RR. Our study suggests an exceptional performance of metal-doped nitrogen-coordinated graphene electrodes, especially 3N-coordinated graphene electrodes.
Oxidative Imbalance in Candida tropicalis Biofilms and Its Relation With Persister Cells

Background Persister cells (PCs) make up a small fraction of microbial population, can survive lethal concentrations of antimicrobial agents. In recent years, Candida tropicalis has emerged as being a frequent fungal agent of medical devices subject to biofilm infections. However, PCs are still poorly understood. Objectives This study aimed to investigate the relation of PCs on the redox status in C. tropicalis biofilms exposed to high doses of Amphotericin B (AmB), and alterations in surface topography and the architecture of biofilms. Methods We used an experimental model of two different C. tropicalis biofilms exposed to AmB at supra minimum inhibitory concentration (SMIC80), and the intra- and extracellular reactive oxygen species (iROS and eROS), reactive nitrogen species (RNS) and oxidative stress response were studied. Light microscopy (LM) and confocal laser scanning microscopy (CLSM) were also used in conjunction with the image analysis software COMSTAT. Results We demonstrated that biofilms derived from the PC fraction (B2) showed a higher capacity to respond to the stress generated upon AmB treatment, compared with biofilms obtained from planktonic cells. In B2, a lower ROS and RNS accumulation was observed in concordance with higher activation of the antioxidant systems, resulting in an oxidative imbalance of a smaller magnitude compared to B1. LM analysis revealed that the AmB treatment provoked a marked decrease of biomass, showing a loss of cellular aggrupation, with the presence of mostly yeast cells. Moreover, significant structural changes in the biofilm architecture were noted between both biofilms by CLSM—COMSTAT analysis. For B1, the quantitative parameters bio-volume, average micro-colony volume, surface to bio-volume ratio and surface coverage showed reductions upon AmB treatment, whereas increases were observed in roughness coefficient and average diffusion distance. In addition, untreated B2 was substantially smaller than B1, with less biomass and thickness values. The analysis of the above-mentioned parameters also showed changes in B2 upon AmB exposure. Conclusion To our knowledge, this is the first study that has attempted to correlate PCs of Candida biofilms with alterations in the prooxidant-antioxidant balance and the architecture of the biofilms. The finding of regular and PCs with different cellular stress status may help to solve the puzzle of biofilm resistance, with redox imbalance possibly being an important factor.
IL-21–Deficient T Follicular Helper Cells Support B Cell Responses Through IL-27 in Patients With Chronic Hepatitis B

Chronic Hepatitis B (CHB) affects over 350 million people worldwide. Current treatment does result in reduced complications; however, a cure (development of antibodies to the S antigen) is not achieved, requiring life-long therapy. Humoral responses contribute to viral elimination by secreting neutralizing antibodies; though, effective induction of humoral immunity require CD4T cell differentiation into T follicular helper (TFH) cells that support B cell response through interleukin-21 (IL-21). In CHB, mechanism of TFH-B interactions is seldom described. During CHB, TFH cells are defective in producing IL-21 in response to hepatitis B surface antigen (HBsAg). However, regardless of low IL-21, TFH cells efficiently support B cell responses by producing interleukin-27 (IL-27), which directs the formation of plasmablasts and plasma cells from memory and naïve B cells by enhancing B lymphocyte-induced maturation protein-1. IL-27 not only improved total antibody production but HBsAg-specific IgG and IgM secretion that are essential for viral clearance. Importantly, IL-27+TFH cells were significantly associated with HBV DNA reduction. Therefore, these findings imply a novel mechanism of TFH mediated B cell help in CHB and suggest that IL-27 effectively compensate the function of IL-21 by supporting TFH-B cell function, required for protective antibody response and may contribute to viral clearance by providing potential target for achieving a functional cure.
Radiocarbon Dating for the Reconstruction of the 1717 CE Triolet Rock Avalanche in the Mont Blanc Massif, Italy

The Arp Nouva peat bog located in the upper Ferret Valley in the Mont Blanc massif was critically evaluated since published radiocarbon dates have led to controversial conclusions on the formation of this swamp. Radiocarbon dating of woody fragments from three pits of up to 1 m depth was used to discuss the question of whether the historically documented rock avalanche occurring in 1717 CE overran the peat bog or settled prior to its formation. For the deepest samples in the pits, calibrated radiocarbon ages between 1,652 and 1950 CE (95.4%; confidence level) were obtained, which fit very well into the time frame of the historical documented 1717 CE rock avalanche event. It can, therefore, be concluded that the Arp Nouva peat bog was formed by blockage of the Bella Combe torrent by the rock avalanche deposits. Furthermore, careful sample preparation with consequent separation of woody fragments from the bulk peat sample has shown that the problem of too old 14C ages can be circumvented. This work demonstrates that a combined geomorphological and geochronological approach is the most reliable way to reconstruct landscape evolution. The key to successful 14C dating is careful sample selection and the identification of the material that might not be ideal for chronological reconstructions.
Local Polymer Dynamics and Diffusion in Cylindrical Nanoconfinement

The melt diffusion of polymers confined to nanoscale cylinders was investigated by molecular dynamics simulations and depth profiling experiments. In the simulations, entangled polymers are confined within long cylindrical pores having effective diameters (deff) from 0.4Ree to 1.7Ree, where Ree is the square root of the mean-squared end-to-end distance of the polymer in the absence of confinement. The local dynamics of polymers confined to cylinders exhibit anisotropic relaxations. Perpendicular to the cylindrical axis, monomer motion is suppressed by the adjacent wall, while motion along the cylindrical axis is faster relative to the bulk dynamics. These anisotropic relaxations are discussed in light of our prior studies showing that chain conformations parallel to the cylinder axis are elongated relative to the bulk conformation, whereas in the perpendicular direction the chain conformations are compressed. Furthermore, our previous simulations found that the number of entanglements per chain decreases .
Spindle Architectural Features Must Be Considered Along With Cell Size to Explain the Timing of Mitotic Checkpoint Silencing

Mitosis proceeds through a defined series of events that is largely conserved, but the amount of time needed for their completion can vary in different cells and organisms. In many systems, mitotic duration depends on the time required to satisfy and silence the spindle assembly checkpoint (SAC), also known as the mitotic checkpoint. Because SAC silencing involves trafficking SAC molecules among kinetochores, spindle, and cytoplasm, the size and geometry of the spindle relative to cell volume are expected to affect mitotic duration by influencing the timing of SAC silencing. However, the relationship between SAC silencing, cell size, and spindle dimensions is unclear. To investigate this issue, we used four DLD-1 tetraploid (4N) clones characterized by small or large nuclear and cell size. We found that the small 4N clones had longer mitotic durations than the parental DLD-1 cells and that this delay was due to differences in their metaphase duration. Leveraging a previous mathematical model for spatiotemporal regulation of SAC silencing, we show that the difference in metaphase duration, i.e., SAC silencing time, can be explained by the distinct spindle microtubule densities and sizes of the cell, spindle, and spindle poles in the 4N clones. Lastly, we demonstrate that manipulating spindle geometry can alter mitotic and metaphase duration, consistent with a model prediction. Our results suggest that spindle size does not always scale with cell size in mammalian cells and cell size is not sufficient to explain the differences in metaphase duration. Only when a number of spindle architectural features are considered along with cell size can the kinetics of SAC silencing, and hence mitotic duration, in the different clones be explained.