Miracle-dz/UniFAR-FTUs huggingface dataset:
Thrombosis in Covid-19 and non-Covid-19 pneumonia: role of platelets

Abstract Platelets may be a target of bacteria and viruses, which can directly or indirectly activate them so promoting thrombosis. In accordance with this, community-acquired pneumonia (CAP) is complicated by ischemia-related vascular disease (myocardial infarction and stroke) in roughly 10% of patients while the incidence of venous thrombosis is uncertain. In CAP platelet biosynthesis of TxA2 is augmented and associated with myocardial infarction; however, a cause-effect relationship is still unclear as unclear is if platelet activation promotes thrombosis or functional changes of coronary tree such vasospasm. Retrospective studies suggested a potential role of aspirin in reducing mortality but the impact on vascular disease is still unknown. Coronavirus disease 2019 (Covid-19) is complicated by thrombosis in roughly 20% of patients with an almost equivalent localization in arterial and venous circulation. Platelet activation seems to have a pivot role in the thrombotic process in Covid-19 as consistently evidenced by its involvement in promoting Tissue Factor up-regulation via leucocyte interaction. Until now, antiplatelet treatment has been scarcely considered for the treatment of Covid-19; interventional trials, however, are in progress to explore this issue. The aim of this review is 1) to compare the type of vascular diseases complicating CAP and Covid-19 2) to assess the different role of platelets in both diseases and 3) to discuss if antiplatelet treatment is potentially useful to improve clinical outcomes.
Sustainable Drinking Water Treatment: Using Weak Base Anion Exchange Sorbents Embedded with Metal Oxide Nanoparticles to Simultaneously Remove Multiple Oxoanions

Sustainable production of microalgae for biofuel requires efficient phosphorus (P) utilization, which is a limited resource and vital for global food security. This research tracks the fate of P through biofuel production and investigates P recovery from the biomass using the cyanobacterium Synechocystis sp. PCC 6803. Our results show that Synechocystis contained 1.4% P dry weight. After crude lipids were extracted (e.g., for biofuel processing), 92% of the intracellular P remained in the residual biomass, indicating phospholipids comprised only a small percentage of cellular P. We estimate a majority of the P is primarily associated with nucleic acids. Advanced oxidation using hydrogen peroxide and microwave heating released 92% of the cellular P into orthophosphate. We then recovered the orthophosphate from the digestion matrix using two different types of anion exchange resins. One resin impregnated with iron nanoparticles adsorbed 98% of the influent P through 20 bed volumes, but only released 23% during regeneration. A strong-base anion exchange resin adsorbed 87% of the influent P through 20 bed volumes and released 50% of it upon regeneration. This recovered P subsequently supported growth of Synechocystis. This proof-of-concept recovery process reduced P demand of biofuel microalgae by 54%.
A Wnt-Independent LGR4–EGFR Signaling Axis in Cancer Metastasis

This work demonstrates a Wnt-independent mechanism by which LGR4 promotes cancer metastasis. Leucine-rich repeat-containing G protein–coupled receptors 4, 5, and 6 (LGR4/5/6) play critical roles in development and cancer. The widely accepted mechanism is that these proteins, together with their R-spondin ligands, stabilize Wnt receptors, thus potentiating Wnt signaling. Here we show that LGR4 enhanced breast cancer cell metastasis even when Wnt signaling was deactivated pharmacologically or genetically. Furthermore, LGR4 mutants that cannot potentiate Wnt signaling nevertheless promoted breast cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Multiomic screening identified EGFR as a crucial mediator of LGR4 activity in cancer progression. Mechanistically, LGR4 interacted with EGFR and blocked EGFR ubiquitination and degradation, resulting in persistent EGFR activation. Together, these data uncover a Wnt-independent LGR4–EGFR signaling axis with broad implications for cancer progression and targeted therapy. Significance: This work demonstrates a Wnt-independent mechanism by which LGR4 promotes cancer metastasis. See related commentary by Stevens and Williams, p. 4397
A Novel Virus of Flaviviridae Associated with Sexual Precocity in Macrobrachium rosenbergii

The iron prawn syndrome (IPS), also described as sexual precocity, results in the reduced size of farmed prawns at harvest and significant economic losses. IPS has been frequently reported in populations of farmed Macrobrachium rosenbergii since 2010, but the cause was heretofore unknown. ABSTRACT Since 2010, sexual precocity, a typical sign of the iron prawn syndrome (IPS), resulting in the reduced size of farmed giant freshwater prawns Macrobrachium rosenbergii, has caused substantial production losses. However, the cause of IPS was not clear. We ran tests for eight major shrimp pathogens, but none were detected from IPS-affected prawns. We performed the histopathological examination of tissues and identified an eosinophilic inclusion in the perinuclear cytoplasm of cells in various tissues associated with nervous and endocrinal functions in the compound eyes. A subsequent bioassay with viral extracts of IPS-affected samples reproduced the gross signs of IPS. Metatranscriptomic sequencing identified a novel virus of Flaviviridae in all IPS-affected M. rosenbergii prawns, which was not found in samples without IPS. This virus contains a positive-sense, single-stranded RNA genome of 12,630 nucleotides (nt). Phylogenetic analysis of the conserved RdRp and NS3 domains showed that it may belong to a new genus between Jingmenvirus and Flavivirus. Under transmission electron microscopy (TEM), putative virus particles showed as spherical with a diameter of 40 to 60 nm. In situ hybridization found hybridization signals consistent with the histopathology in the compound eyes from IPS-affected M. rosenbergii. We provisionally name this virus infectious precocity virus (IPV) and propose the binominal Latin name Crustaflavivirus infeprecoquis gen. nov., sp. nov. We developed a nested reverse transcription-PCR diagnostic assay and confirmed that all IPS-affected prawns tested IPV positive but normal prawns tested negative. Collectively, our study revealed a novel virus of Flaviviridae associated with sexual precocity in M. rosenbergii. IMPORTANCE The iron prawn syndrome (IPS), also described as sexual precocity, results in the reduced size of farmed prawns at harvest and significant economic losses. IPS has been frequently reported in populations of farmed Macrobrachium rosenbergii since 2010, but the cause was heretofore unknown. Here, we reported a novel virus identified from prawns with IPS using infection experiments, metatranscriptomic sequencing, and transmission electron microscopy and provisionally named it infectious precocity virus (IPV). Phylogenetic analysis showed that IPV represents a new genus, proposed as Crustaflavivirus gen. nov., in the family Flaviviridae. This study provides novel insight that a viral infection may cause pathological change and sexual maturation and subsequently affect crustacean growth. Therefore, we call for quarantine inspection of IPV in transboundary trade of live M. rosenbergii and enhanced surveillance of IPV in aquaculture in the region and globally.
Construction of DNA Tools for Hyperexpression in Marchantia Chloroplasts

Chloroplasts are attractive platforms for synthetic biology applications since they are capable of driving very high levels of transgene expression, if mRNA production and stability are properly regulated. However, plastid transformation is a slow process and currently limited to a few plant species. The liverwort Marchantia polymorpha is a simple model plant that allows rapid transformation studies; however, its potential for protein hyperexpression has not been fully exploited. This is partially due to the fact that chloroplast post-transcriptional regulation is poorly characterized in this plant. We have mapped patterns of transcription in Marchantia chloroplasts. Furthermore, we have obtained and compared sequences from 51 bryophyte species and identified putative sites for pentatricopeptide repeat protein binding that are thought to play important roles in mRNA stabilization. Candidate binding sites were tested for their ability to confer high levels of reporter gene expression in Marchantia chloroplasts, and levels of protein production and effects on growth were measured in homoplastic transformed plants. We have produced novel DNA tools for protein hyperexpression in this facile plant system that is a test-bed for chloroplast engineering.
Fyn Knock-Down Prevents Levodopa-Induced Dyskinesia in a Mouse Model of Parkinson’s Disease

Visual Abstract Dopamine replacement by levodopa (L-DOPA) is the most widely used therapy for Parkinson’s disease (PD), however patients often develop side effects, known as L-DOPA-induced dyskinesia (LID), that usually need therapeutic intervention. There are no suitable therapeutic options for LID, except for the use of the NMDA receptor (NMDA-R) antagonist amantadine, which has limited efficacy. The NMDA-R is indeed the most plausible target to manage LID in PD and recently the kinase Fyn, one of its key regulators, became a new putative molecular target involved in LID. The aim of this work was to reduce Fyn expression to alleviate LID in a mouse model of PD. We performed intrastriatal delivery of a designed micro-RNA against Fyn (miRNA-Fyn) in 6-OHDA-lesioned mice treated with L-DOPA. The miRNA-Fyn was delivered either before or after L-DOPA exposure to assess its ability to prevent or revert dyskinesia. Preadministration of miRNA-Fyn reduced LID with a concomitant reduction of FosB-ΔFosB protein levels, a marker of LID, as well as decreased phosphorylation of the NR2B-NMDA subunit, which is a main target of Fyn. On the other hand, post-L-DOPA delivery of miRNA-Fyn was less effective to revert already established dyskinesia, suggesting that early blocking of Fyn activity might be a more efficient therapeutic approach. Together, our results provide proof of concept about Fyn as a plausible therapeutic target to manage LID, and validate RNA silencing as a potential approach to locally reduce striatal Fyn, rising new perspectives for RNA therapy interventions in PD.
Therapeutic Effects of Add-On Tenapanor for Hemodialysis Patients with Refractory Hyperphosphatemia

Introduction: Phosphate binders are used to treat hyperphosphatemia. Some patients have inappropriately controlled serum phosphorus levels, which may occur for many reasons, including a high pill burden and adverse events (AEs). Tenapanor selectively inhibits the passive paracellular transfer of phosphate in the gastrointestinal tract, thereby reducing serum phosphorus levels. This novel mechanism of action may contribute to improved phosphate management. The efficacy and safety of tenapanor have not been evaluated in Japanese patients with high serum phosphorus levels despite treatment with phosphate binders. This study aimed to assess the efficacy and safety of add-on tenapanor therapy for reducing serum phosphorus levels in this population. Methods: This multicenter, double-blind, randomized, placebo-controlled trial enrolled patients with refractory hyperphosphatemia undergoing hemodialysis. Patients were randomly assigned in a 1:1 ratio to receive tenapanor or placebo as an add-on to their phosphate binder regimen for 6 weeks. Change in serum phosphorus levels at week 6 (day 43) compared with the baseline value (day 1, week 0) (primary endpoint), achievement of target serum phosphorus levels (serum phosphorus level ≤6.0 or ≤5.5 mg/dL), and safety, based on all AEs and drug-related AEs, were among the outcomes evaluated. Results: In total, 24 patients were randomly assigned to the placebo group and 23 to the tenapanor group. The mean serum phosphorus level decreased from 7.01 mg/dL on day 1 to 6.69 mg/dL on day 43 in the placebo group and from 6.77 mg/dL on day 1 to 4.67 mg/dL on day 43 in the tenapanor group. In the placebo and tenapanor groups (modified intent-to-treat population), the mean (standard deviation) change in the serum phosphorus level at day 43 (last observation carried forward [LOCF]) was 0.08 (1.52) mg/dL and −1.99 (1.24) mg/dL, respectively, with a between-group difference of −2.07 (95% confidence interval: −2.89, −1.26; p < 0.001). The target achievement rate (serum phosphorus level ≤6.0 mg/dL at week 6 [LOCF]) was 37.5 and 87.0% in the placebo and tenapanor groups, respectively. Diarrhea was the most common drug-related AE, and it occurred in 8.3 and 65.2% of patients in the placebo and tenapanor groups, respectively. No specific AEs were observed with add-on tenapanor or with phosphate binders. Discussion/Conclusion: Therapy with existing phosphate binders and add-on tenapanor resulted in a significant decrease in serum phosphorus level compared with the placebo group in patients with refractory hyperphosphatemia despite treatment with phosphate binders. No new safety signals were raised, and add-on tenapanor was generally well tolerated.
Aerobic exercise, cardiorespiratory fitness, and the human hippocampus

The hippocampus is particularly susceptible to neurodegeneration. Physical activity, specifically increasing cardiorespiratory fitness via aerobic exercise, shows promise as a potential method for mitigating hippocampal decline in humans. Numerous studies have now investigated associations between the structure and function of the hippocampus and engagement in physical activity. Still, there remains continued debate and confusion about the relationship between physical activity and the human hippocampus. In this review, we describe the current state of the physical activity and exercise literature as it pertains to the structure and function of the human hippocampus, focusing on four magnetic resonance imaging measures: volume, diffusion tensor imaging, resting‐state functional connectivity, and perfusion. We conclude that, despite significant heterogeneity in study methods, populations of interest, and scope, there are consistent positive findings, suggesting a promising role for physical activity in promoting hippocampal structure and function throughout the lifespan.
Different feeding regimens were not associated with variation in body composition in preterm infants

Abstract Aim The aim was to determine body composition and growth in preterm infants based on two different feeding regimens and to assess how standard and individual fortification (IF) affect energy and protein intake. Body composition was assessed at full term and at four months corrected age. Methods Sixty preterm infants born before gestational week 32 were randomized either to IF of mother’s breast milk after it had been analyzed or to standard fortification (SF) of mother’s breast milk based on the average protein and energy content of breast milk. Body composition was measured at full term and at four months corrected age, using air displacement plethysmography. Growth rate and nutritional intake analyses were also conducted. Results At 40 weeks gestational age, there was no difference between weight (g) (IF 3056 ± 472 vs. SF 3119 ± 564), body fat (%) (IF 19 ± 3.3 vs. SF 21 ± 5.6), fat mass, or fat-free mass between the two groups. Furthermore, there was no difference between the groups in weight, length, head circumference, or body composition at four months corrected age. Conclusions Fortification based on breast milk analysis may not improve growth in preterm infants compared to SF. However, both groups were smaller and had a different body composition at term corrected age compared to infants born at term.
Ochratoxin A induces human kidney tubular epithelial cell apoptosis through regulating lipid raft/PTEN/AKT signaling pathway

Ochratoxin A (OTA) is a fungal toxin that causes serious threat to human health. OTA could lead to the injury of various tissues, especially kidney injury. However, the toxic effects of OTA on human kidney tubular epithelial cell (HK‐2) and the possible mechanism remains poorly understood. This study was to investigate the toxic effects of OTA on HK‐2 and elucidate the molecular mechanism. HK‐2 cells were treated OTA to evaluate the effect of OTA on cell viability and apoptosis. OTA inhibited the growth of HK‐2 in a concentration‐dependent manner. With the concentration increased, OTA significantly lead to the apoptosis of HK‐2. OTA could increase the levels of reactive oxygen species (ROS) and Malondialdehyde (MDA). Superoxide dismutase (SOD) and glutathione (GSH) activities were decreased by OTA. Furthermore, OTA increased Caspase‐3 and Bax expression and decreased BCL2 expression. Compared to the control group, the expression of PTEN was increased and the expression of PI3K and AKT were decreased in OTA treated groups. In addition, we found OTA could disrupt the formation of lipid raft by attenuating sphingomyelin and cholesterol levels. In conclusion, our results indicated that OTA induces apoptosis in HK‐2 through regulating PTEN/AKT signaling pathway via disrupting lipid raft formation.
Enduring life in between a sense of renewal and loss of courage: lifeworld perspectives one year after hip fracture

ABSTRACT Purpose: To explore everyday life experiences of being active in aged adults´ with walking impairment one year after hip fracture (HF). Methods: A phenomenological-hermeneutic study design is based on Heidegger´s and Gadamer´s thinking focusing on aged adults being-in-the-world one year after HF. Individual semi-structured interviews were conducted from May to July 2017 in the homes of nine participants, who were part of a longitudinal qualitative study with four interview-rounds for a period of 18 months after the HF event. The analysis was interpretative and secured that the authors´ pre-understanding was put at stake through a five-step process of meaning condensation. Results: One theme, “Enduring life in between a sense of renewal and loss of courage”, described aged adults´ experiences of being active in three sub-themes: “Facing loss and losing courage”, “Taking up the challenge and maintaining courage “, and “Renewing the energy to be active”. Living with being under change and increased vulnerability created a challenge in maintaining courage and reaching for possibilities to unfold their own being in life. Conclusion: This study contributes knowledge on how the aged adults´ experiences of the balance between courage and loss in being active one year after HF are profoundly connected with experiences of well-being.
Finite-Time Heterogeneous Cyclic Pursuit With Application to Cooperative Target Interception

This article presents a finite-time heterogeneous cyclic pursuit scheme that ensures consensus among agents modeled as integrators. It is shown that for the proposed consensus scheme, even when the gains are nonidentical, consensus results within a finite time, provided all the gains are positive or even if one gain is negative, subject to a lower bound. An algorithm is presented to compute the consensus value and consensus time for a given set of positive gains and initial states of the agents. The set of values, where consensus can occur, by varying the gains, has been derived and a second algorithm aids in determining the positive gains that enable consensus at any point in the aforementioned set, at a given finite time. As an application, the finite-time consensus in line-of-sight rates, over a cycle digraph, for a group of interceptors is shown to be effective in ensuring co-operative collision-free interception of a target, for both constant speed as well as realistic time-varying-speed models of the interceptors. Simulations the theoretical results.
Conserved Modules Required for Drosophila TRP Function in Vivo

Transient receptor potential (TRP) channels are broadly required in animals for sensory physiology. To provide insights into regulatory mechanisms, the structures of many TRPs have been solved. This has led to new models, some of which have been tested in vitro. Here, using the classical TRP required for Drosophila visual transduction, we uncovered structural requirements for channel function in photoreceptor cells. Using a combination of molecular genetics, field recordings, protein expression analysis, and molecular modeling, we interrogated roles for the S4–S5 linker and the TRP domain, and revealed mutations in the S4–S5 linker that impair channel opening or closing. We also uncovered differential requirements for the two highly conserved motifs in the TRP domain for activation and protein stability. By performing genetic complementation, we found an intrasubunit interaction between the S4–S5 linker and the S5 segment that contributes to activation. This analysis highlights key structural requirements for TRP channel opening, closing, folding, and for intrasubunit interactions in a native context—Drosophila photoreceptor cells. SIGNIFICANCE STATEMENT The importance of TRP channels for sensory biology and human health has motivated tremendous effort in trying to understand the roles of the structural motifs essential for their activation, inactivation, and protein folding. In the current work, we have exploited the unique advantages of the Drosophila visual system to reveal mechanistic insights into TRP channel function in a native system–photoreceptor cells. Using a combination of electrophysiology (field recordings), cell biology, and molecular modeling, we have revealed roles of key motifs for activation, inactivation and protein folding of TRP in vivo.
Health Professionals’ Recommendations for a Dementia Plan for China

There is no specific national dementia plan concerning people with dementia in China. The purpose of this study was to explore health professionals’ recommendations for a dementia plan for China to meet the needs of people with dementia. Semi-structured interviews were conducted with 24 doctors and nurses using purposive maximum variation sampling. Data were interpreted inductively using thematic analysis. Four themes were identified. Themes on policy recommendations emphasized a need to support people with dementia and those who care for them, including the development of community daycare centers, specialized dementia care units in hospitals, and specialized nursing homes. Improvement in dementia care in China is needed, including services across all care settings. Programs to train and support family caregivers and help health professionals to detect, diagnose and treat dementia are crucial. Further support for the families of people with dementia is required.