Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating Stored Platelet Shape Change Using Imaging Flow Cytometry

Platelets are routinely stored at room temperature for 5-7 days before transfusion. Stored platelet quality is traditionally assessed by Kunicki’s morphology score. This method requires extensive training, experience, and is highly subjective. Moreover, the number of laboratories familiar with this technique is decreasing. Cold storage of platelets has recently regained interest because of potential advantages such as reduced bacterial growth and preserved function. However, platelets exposed to cold temperatures change uniformly from a discoid to a spherical shape, reducing the morphology score outcomes to a binary “spheres versus discs” during cooling. We developed a simpler, unbiased screening tool to measure temperature-induced platelet shape change using imaging flow cytometry. When reduced to two dimensions, spheres appear circular, while discs are detected on a spectrum from fusiform to circular. We defined circular events as having a transverse axis of > 0.8 of the longitudinal axis and fusiform events ≤ 0.8 of the longitudinal axis. We show that most EGTA-treated platelets and spherical beads are detected in the gate for circular events, while fresh platelets are found mainly in the gate for fusiform events. Using this assay, mouse and human platelets show a temperature and time-dependent, two-dimensional shape change from fusiform to circular, consistent with their three-dimensional change from discs to spheres. The method we describe here is a valuable tool for detecting shape change differences in response to agonists or temperature and will help screen for therapeutic measures to mitigate the cold-induced storage lesion. Plain language summary What is the context? Platelets for transfusion are currently stored for 5-7 days at room temperature, increasing the risk for bacterial growth Cold storage reduces the risk for bacterial growth but reduces circulation time Stored platelet quality can be assessed by the light microscopy-based Morphology Score, first described in the 1970s Downsides of the Morphology Score include subjectivity, extensive training, and reduced availability in platelet laboratories. What is new? In this study, we provide data showing that the Morphology score is reduced to a binary spheres versus discs response in cold-exposed platelets We developed an imaging flow cytometry-based approach to quantify platelets’ response to cold based on the two-dimensional projection of the three-dimensional shapes, i.e., fusiform (discoid) versus circular (discoid and spherical) We provide validation of this approach in mouse and human platelets We provide evidence for increased temperature sensitivity in mouse platelets What is the impact? This study provides an easy and unbiased tool for laboratories working on circumventing the cold-induced storage lesion or documenting spherical shape change in general
Asymmetric signaling across the hierarchy of cytoarchitecture within the human connectome

Cortical variations in cytoarchitecture form a sensory-fugal axis that systematically shapes regional profiles of extrinsic connectivity. Additionally, this axis is thought to guide signal propagation and integration across the cortical hierarchy. While human neuroimaging work has shown that this axis constrains local properties of the human connectome, it remains unclear whether it also shapes the asymmetric signaling that arises from higher-order connectome topology. Here, we used network control theory to examine the amount of energy required to propagate dynamics across the sensory-fugal axis. Our results revealed an asymmetry in this energy indicating that bottom-up transitions were easier to complete compared to top-down transitions. Supporting analyses demonstrated that this asymmetry was underpinned by a connectome topology that is wired to support efficient bottom-up signaling. Finally, we found that this asymmetry correlated with changes in intrinsic neuronal timescales and lessened throughout youth. Our results show that cortical variation in cytoarchitecture may guide the formation of macroscopic connectome topology.
Fat body-specific reduction of CTPS alleviates HFD-induced obesity

High fat diet (HFD)-induced obesity is a multi-factorial disease including genetic, physiological, behavioral, and environmental components. Drosophila has emerged as a useful model of metabolic diseases. Cytidine 5′-triphosphate synthase (CTPS) is a key enzyme for the de novo synthesis of CTP, governing cellular level of CTP and phospholipid synthesis. We have demonstrated that CTPS show the capacity to assemble into large filaments termed cytoophidia, which are evolutionarily conserved in bacteria, archaea and eukaryotes. Here, we show that CTPS acts in fat body to regulate body weight and starvation resistant in Drosophila. HFD-induced obesity elevates CTPS transcription and elongates cytoophidia in larval adipocytes. Fat body-specific depletion of CTPS alleviated HFD-induced obesity including body weight gain, lipid storage and TAG level. Moreover, a dominant negative form of CTPS reduces lipid accumulation and down regulates lipogenic genes. Therefore, our data not only provide a functional link between CTPS and lipid homeostasis, but also highlight the potential application of manipulating CTPS in the treatment of HFD-induced obesity.
Hypoxic memory of tumor intrinsic type I interferon suppression promotes breast cancer metastasis

Hypoxia is a common feature of many solid tumors due to aberrant proliferation and angiogenesis and has been associated with tumor progression and metastasis. Most of the well-known hypoxia effects are mediated through hypoxia-inducible factors (HIFs), but the long-lasting effect of hypoxia beyond the immediate HIF regulation remains less understood. Here we show that hypoxia exerts a prolonged effect to promote metastasis. Using breast cancer patient-derived circulating tumor cell (CTC) lines and common breast cancer cell lines, we found that hypoxia downregulates tumor intrinsic type I interferon (IFN) signaling and its downstream antigen presentation (AP) machinery in luminal breast cancer cells, via both HIF-dependent and HIF-independent mechanisms. Hypoxia induced IFN/AP suppression can last longer than the hypoxic exposure, presenting a “hypoxic memory” phenotype. Hypoxic memory of IFN/AP downregulation is established by specific hypoxic priming, and cells with hypoxic memory have an enhanced ability for tumorigenesis and metastasis. The histone deacetylase inhibitor (HDACi) Entinostat can erase the hypoxic memory and improve the immune clearance of tumor cells when combined with checkpoint immunotherapies in a syngeneic breast cancer mouse model. These results point to a novel mechanism for hypoxia facilitated tumor progression, through a long-lasting memory that provides advantages for CTCs during the metastatic cascade. Significance: We revealed a novel hypoxic memory of prolonged suppression of tumor intrinsic type I IFN and AP signals that promote tumorigenesis and metastasis, suggesting novel mechanistic understanding of the immune evasive properties of CTCs.
Surface-Induced cAMP Signaling Requires Multiple Features of the Pseudomonas aeruginosa Type IV Pili

Surface sensing by P. aeruginosa requires TFP. TFP plays a critical role in the induction of the second messenger cAMP upon surface contact; this second messenger is part of a larger cascade involved in the transition from a planktonic to a biofilm lifestyle. ABSTRACT Pseudomonas aeruginosa type IV pili (TFP) are important for twitching motility and biofilm formation. TFP have been implicated in surface sensing, a process whereby surface-engaged cells upregulate the synthesis of the second messenger cAMP to propagate a signaling cascade leading to biofilm initiation and repression of motility. Here, we showed that mutations in PilA impairing proteolytic processing of the prepilin into mature pilin as well as the disruption of essential TFP components, including the PilC platform protein and PilB assembly motor protein, fail to induce surface-dependent cAMP signaling. We showed that TFP retraction by surface-engaged cells was required to induce signaling and that the retractile motor PilT was both necessary and sufficient to power surface-specific induction of cAMP. Furthermore, full TFP function required to support twitching motility is not required for robust cAMP signalling. The PilU retraction motor, in contrast, was unable to support full signaling in the absence of PilT. Finally, while we confirmed that PilA and PilJ interacted by bacterial two-hybrid analysis, our data do not support the current model that PilJ-PilA interaction drives cAMP signaling. IMPORTANCE Surface sensing by P. aeruginosa requires TFP. TFP plays a critical role in the induction of the second messenger cAMP upon surface contact; this second messenger is part of a larger cascade involved in the transition from a planktonic to a biofilm lifestyle. Here, we showed that TFP must be deployed and actively retracted by the PilT motor for the full induction of cAMP signaling. Furthermore, the mechanism whereby TFP retraction triggers cAMP induction is not well understood, and our data argue against one of the current models in the field proposed to address this knowledge gap.
Distinct population and single-neuron selectivity for executive and episodic processing in human dorsal posterior cingulate

Posterior cingulate cortex (PCC) is an enigmatic region implicated in psychiatric and neurological disease, yet its role in cognition remains unclear. Human studies link PCC to episodic memory and default mode network (DMN), while findings from the non-human primate emphasize executive processes more associated with the cognitive control network (CCN) in humans. We hypothesized this difference reflects an important functional division between dorsal (executive) and ventral (episodic) PCC. To test this, we utilized human intracranial recordings of population and single unit activity targeting dorsal PCC during an alternated executive/episodic processing task. Dorsal PCC population responses were significantly enhanced for executive, compared to episodic, task conditions, consistent with the CCN. Single unit recordings, however, revealed four distinct functional types with unique executive (CCN) or episodic (DMN) response profiles. Our findings provide critical electrophysiological data from human PCC, bridging incongruent views within and across species, furthering our understanding of PCC function.
Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens

The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID- 19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV2. S and two-dose ChAdOx1 or combination ChAdOx1/mRNA vaccination. Plasma neutralizing activity as well as the magnitude, clonal composition and antibody maturation of the RBD-specific memory B cell compartment showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS-CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV2. S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.
Distribution Characteristics of Soil Particles and Their Relationships With Soil Organic Carbon Components in the Alluvial/Sedimentary Zone in the Lower Reaches of the Yellow River

Land use and sediment alluviation/deposition are the main factors influencing the vertical distributions of particles with different sizes and soil organic carbon (SOC) forms. Based on field investigation, experimental analysis, data analysis, soil particle characteristics, and the relationships with SOC compositions are studied in the typical alluviation/deposition area of Kaifeng–Zhoukou. In the soil profile, the particulate matter is mainly 10–50 μm and 50–250 μm in size with an average content of approximately 65%, the content difference within the same size particle range is small. There is a large content range of <1,000 μm particles, which is the main factor affecting the change in soil properties. The fractal dimension (D) of soil particles ranges from 2.21 to 2.78. The value of D of each layer in farmland is higher than that of each layer in woodland, and it has been observed that D NF(farmland in the nonflooded area) > D F(farmland in the flooded area) and D NW(woodland in the nonflooded area) > D W(farmland in the nonflooded area). The contents of particles smaller than 50 μm have a positive effect on D, and the particles exceeding 50 μm have a negative effect. The contents of 10–50 μm, <2 μm, 2–5 μm, and 5–10 μm particles and their dynamic variances are the root causes of the D differences in the farmland/woodland soil in the FA (the flooded area) and NFA (the nonflooded area). SOC components combine to a greater extent with silt and clay that are <10 μm in size in the NF, and the stability is relatively high. The contents of the 10–50 μm and <10 μm particles are the main reasons for the differences in the soil active and nonactive organic carbon (AOC and NOC, respectively) contents in the FA and the NFA. The difference in D can reflect the change in SOC and its components and can be used as an index to characterize the variance in soil properties and quality. This study revealed the influences of the different particle sizes in the SOC components, which will expand and enrich the current area of study and further provide a basis to increase SOC and improve soil quality.
Comprehensive Analysis of a Ferroptosis Pattern and Associated Prognostic Signature in Acute Myeloid Leukemia

Ferroptosis is a widespread form of programmed cell death. The environment of cancer cells makes them vulnerable to ferroptosis, including AML cells, yet the specific association between ferroptosis and AML outcome is little known. In this study, we utilized ferroptosis-related genes to distinguish two subtypes in TCGA cohort, which were subsequently validated in independent AML cohorts. The subtypes were linked with tumor-related immunological abnormalities, mutation landscape and pathway dysregulation, and clinical outcome. Further, we developed a 13-gene prognostic model for AML from DEG analysis in the two subtypes. A risk score was calculated for each patient, and then the overall group was stratified into high- and low-risk groups; the higher risk score correlated with short survival. The model was validated in both independent AML cohorts and pan-cancer cohorts, which demonstrated robustness and extended the usage of the model. A nomogram was constructed that integrated risk score, FLT3-ITD, TP53, and RUNX1 mutations, and age. This model had the additional value of discriminating the sensitivity of several chemotherapeutic drugs and ferroptosis inducers in the two risk groups, which increased the translational value of this model as a potential tool in clinical management. Through integrated analysis of ferroptosis pattern and its related model, our work shed new light on the relationship between ferroptosis and AML, which may facilitate clinical application and therapeutics.
Do Immediate External Rewards Really Enhance Intrinsic Motivation?

Researchers have conducted many studies on the relationship between external rewards and intrinsic motivation. A recent study showed that, compared with delayed rewards, rewards delivered immediately after the experiment enhanced the participants’ intrinsic motivation. However, this study did not rule out the possibility of a misattribution effect of extrinsic motivation. The present research conducted three studies to explore whether immediate rewards actually enhance intrinsic motivation. To rule out the interference of the misattribution effect of extrinsic motivation, according to the different characteristics of extrinsic motivation and intrinsic motivation, Study 1 and Study 2 improved the prior experimental paradigm, and the results indicated that the intrinsic motivation of participants who received extra rewards immediately after completing experimental tasks was stronger than that of participants who received the delayed extra reward. Furthermore, to rule out the potential interference of temporal discounting, Study 3 introduced a new variable—reward magnitude. The results showed that the delivery time of the extra reward had an independent effect on intrinsic motivation and that the immediacy of the extra reward could enhance intrinsic motivation. In all, the three studies strongly demonstrated that immediate external extra rewards could truly enhance intrinsic motivation.
Smartphone Use Time and Total Screen Time Among Students Aged 10–19 and the Effects on Academic Stress: A Large Longitudinal Cohort Study in Shanghai, China

Objective This study aimed to assess smartphone use time and total screen time among students aged 10–19 in Shanghai, China, and examine their effects on academic stress. Methods Baseline and follow-up surveys were conducted in December 2017 and December 2018, respectively, using a cohort study design with 1,771 participants. Questionnaire surveys and physical examinations of participants were conducted by trained investigators and professional school physicians, respectively. The self-administered questionnaire mainly covered demographic information, academic stress, smartphone use time, total screen time, and other lifestyle behaviors. Results The average smartphone use time of primary, middle, and high school students was 0.76 ± 0.90, 1.34 ± 1.29, and 2.39 ± 1.66 h/day, respectively; total screen time was 2.60 ± 2.63, 2.65 ± 3.39, and 3.52 ± 2.7 h/day, respectively (P < 0.001). The academic stress scores of primary, middle, and high school students were 9.25 ± 3.96, 11.97 ± 4.58, and 15.06 ± 5.10 (out of 30), respectively. The smartphone use time and total screen time were positively associated with academic stress score, with β values of 0.307 (95% CI: 0.164–0.450) and 0.171 (95% CI: 0.088–0.255), respectively. The longer the smartphone use time and total screen time, the higher the risk of abnormal academic stress, with OR values of 1.199 (95% CI: 1.103–1.303) and 1.104 (95% CI: 1.056–1.154), respectively. After stratifying by grade group, positive associations between smartphone use time or total screen time and abnormal academic stress were observed in primary and middle school students; for high school students; however, only smartphone use time had a positive association. Conclusions This study confirmed that the academic stress is widespread among students aged 10–19 in Shanghai, China. From a public health perspective, smartphone use time and total screen time should therefore be restricted for reducing academic stress and preventing related problems among adolescents in Shanghai, China, in school, family, and other environments.
Breast Reconstruction Does Not Affect the Survival of Patients with Breast Cancer Located in the Central and Nipple Portion: A Surveillance, Epidemiology, and End Results Database Analysis

Background Tumors in the central and nipple portion (TCNP) are associated with poor prognosis and aggressive clinicopathological characteristics. The availability and safety of postmastectomy reconstruction in breast cancer patients with TCNP have still not been deeply explored. It is necessary to investigate whether reconstruction is appropriate for TCNP compared with non-reconstruction therapy in terms of survival outcomes. Methods Using the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled TCNP patients diagnosed between the years 2010 and 2016. The propensity score matching (PSM) technique was applied to construct a matched sample consisting of pairs of non-reconstruction and reconstruction groups. Survival analysis was performed with the Kaplan–Meier method. Univariate and multivariate Cox proportional hazard models were applied to estimate the factors associated with breast cancer-specific survival (BCSS) and overall survival (OS). Results In the overall cohort, a total of 6,002 patients were enrolled. The patients in the reconstruction group showed significantly better BCSS (log-rank, p < 0.01) and OS (log-rank, p < 0.01) than those in the non-reconstruction group (832 patients) after PSM. However, the multivariate Cox regression model revealed that breast reconstruction was not associated with worse BCSS and OS of TCNP patients. Conclusion Our study provided a new perspective showing that breast reconstruction did not affect the survival and disease prognosis in the cohort of TCNP patients from SEER databases, compared with non-reconstruction. This finding provides further survival evidence supporting the practice of postmastectomy reconstruction for suitable TCNP patients, especially those with a strong willingness for breast reconstruction.
Programmed Cell Death in Sepsis Associated Acute Kidney Injury

Sepsis-associated acute kidney injury (SA-AKI) is common in patients with severe sepsis, and has a high incidence rate and high mortality rate in ICU patients. Most patients progress to AKI before drug treatment is initiated. Early studies suggest that the main mechanism of SA-AKI is that sepsis leads to vasodilation, hypotension and shock, resulting in insufficient renal blood perfusion, finally leading to renal tubular cell ischemia and necrosis. Research results in recent years have shown that programmed cell death such as apoptosis, necroptosis, pyroptosis and autophagy play important roles. In the early stage of sepsis-related AKI, autophagy bodies form and inhibit various types of programmed cell death. With the progress of disease, programmed cell death begins. Apoptosis promoter represents caspase-8-induced apoptosis and apoptosis effector represents caspase-3-induced apoptosis, however, caspase-11 and caspase-1 regulate gasdermin D-mediated pyroptosis. Caspase-8 and receptor interacting kinase 1 bodies mediate necroptosis. This review focuses on the pathophysiological mechanisms of various programmed cell death in sepsis-related AKI.