Miracle-dz/UniFAR-FTUs huggingface dataset:
Chilling induces unidirectional solute leak through the locust gut epithelia

ABSTRACT Chill-susceptible insects, like the migratory locust, often die when exposed to low temperatures from an accumulation of tissue damage that is unrelated to freezing (chilling injury). Chilling injury is often associated with a loss of ion balance across the gut epithelia. It has recently been suggested that this imbalance is at least partly caused by a cold-induced disruption of epithelial barrier function. Here, we aimed to test this hypothesis in the migratory locust (Locusta migratoria). First, chill tolerance was quantified by exposing locusts to −2°C and recording chill coma recovery time and survival 24 h post-cold exposure. Longer exposure times significantly increased recovery time and caused injury and death. Ion-selective microelectrodes were also used to test for a loss of ion balance in the cold. We found a significant increase of haemolymph K+ and decrease of haemolymph Na+ concentration over time. Next, barrier failure along the gut was tested by monitoring the movement of an epithelial barrier marker (FITC-dextran) across the gut epithelia during exposure to −2°C. We found a significant increase in haemolymph FITC-dextran concentration over time in the cold when assayed in the mucosal to serosal direction. However, when tested in the serosal to mucosal direction, we saw minimal marker movement across the gut epithelia. This suggests that while cold-induced barrier disruption is present, it is apparently unidirectional. It is important to note that these data reveal only the phenomenon itself. The location of this leak as well as the underlying mechanisms remain unclear and require further investigation. Summary: Evidence for the presence of cold-induced paracellular leak along the gut of the migratory locust; this leak is strongest in the mucosal to serosal direction.
Asymmetric Pseudocapacitors Based on Interfacial Engineering of Vanadium Nitride Hybrids

Vanadium nitride (VN) shows promising electrochemical properties as an energy storage devices electrode, specifically in supercapacitors. However, the pseudocapacitive charge storage in aqueous electrolytes shows mediocre performance. Herein, we judiciously demonstrate an impressive pseudocapacitor performance by hybridizing VN nanowires with pseudocapacitive 2D-layered MoS2 nanosheets. Arising from the interfacial engineering and pseudocapacitive synergistic effect between the VN and MoS2, the areal capacitance of VN/MoS2 hybrid reaches 3187.30 mF cm−2, which is sevenfold higher than the pristine VN (447.28 mF cm−2) at a current density of 2.0 mA cm−2. In addition, an asymmetric pseudocapacitor assembled based on VN/MoS2 anode and TiN coated with MnO2 (TiN/MnO2) cathode achieves a remarkable volumetric capacitance of 4.52 F cm−3 and energy density of 2.24 mWh cm−3 at a current density of 6.0 mA cm−2. This work opens a new opportunity for the development of high-performance electrodes in unfavorable electrolytes towards designing high areal-capacitance electrode materials for supercapacitors and beyond.
Early-onset cerebellar ataxia in a patient with CMT2A2

A 9-yr 8-mo-old right-handed female presented with a history of gait difficulties, which first became apparent at age 9 mo of age, along with slurred speech and hand tremors while holding a tray. Her past medical history was significant for global developmental delay, and she was attending fourth grade special education classes. On examination, she had an ataxic gait, dysarthria, absent deep tendon reflexes, and flexor plantar responses. There were no signs of optic atrophy or hearing loss. Nerve conduction studies were consistent with an axonal neuropathy. A fascicular sural nerve biopsy showed a marked decrease of myelinated fibers larger than 6 µm in diameter as compared with an age-matched control. By electron microscopy, clusters of degenerating axonal mitochondria in both myelinated and unmyelinated fibers were frequently found. Whole-exome sequencing revealed a heterozygous c.314C > T (p.Thr105Met) missense variant in MFN2 in the patient but not in her mother. The father was unavailable for testing. The phenotypes with MFN2 variants can be quite variable, including intellectual disability, optic atrophy, auditory impairment, spinal atrophy with or without hydromyelia, and hydrocephalus. We report here that early onset ataxia with intellectual disability can also be associated with MFN2-related Charcot–Marie–Tooth, Type 2A2A diagnosis, the most common type of autosomal dominant axonal neuropathy.
The RNA-binding protein Hfq assembles into foci-like structures in nitrogen starved Escherichia coli

The initial adaptive responses to nutrient depletion in bacteria often occur at the level of gene expression. Hfq is an RNA-binding protein present in diverse bacterial lineages that contributes to many different aspects of RNA metabolism during gene expression. Using photoactivated localization microscopy and single-molecule tracking, we demonstrate that Hfq forms a distinct and reversible focus-like structure in Escherichia coli specifically experiencing long-term nitrogen starvation. Using the ability of T7 phage to replicate in nitrogen-starved bacteria as a biological probe of E. coli cell function during nitrogen starvation, we demonstrate that Hfq foci have a role in the adaptive response of E. coli to long-term nitrogen starvation. We further show that Hfq foci formation does not depend on gene expression once nitrogen starvation has set in and occurs indepen-dently of the transcription factor N-regulatory protein C, which activates the initial adaptive response to N starvation in E. coli. These results serve as a paradigm to demonstrate that bacterial adaptation to long-term nutrient starvation can be spatiotemporally coordinated and can occur independently of de novo gene expression during starvation.
Statin reduces the incidence of diabetic retinopathy and its need for intervention: A systematic review and meta-analysis

Purpose: We aimed to perform a systematic literature search on the latest evidence of the role of statin in reducing diabetic retinopathy and its need for intervention. Methods: A comprehensive search on cohort studies/clinical trials that assess statins and diabetic retinopathy up until August 2019 was performed. The outcome measured was the incidence of diabetic retinopathy and its need for intervention. Results: There were 558.177 patients from six studies. Statin was associated with a lower incidence of diabetic retinopathy (hazard ratio: 0.68 (0.55, 0.84), p < 0.001; I2: 95%). For the subtypes of diabetic retinopathy, statin lowers the incidence of proliferative diabetic retinopathy (hazard ratio: 0.69 (0.51, 0.93), p = 0.01; I2: 90%), non-proliferative diabetic retinopathy (hazard ratio: 0.80 (0.66, 0.96), p = 0.02; I2: 93%), and diabetic macular edema (hazard ratio: 0.56 (0.39, 0.80), p = 0.002; I2: 82%). Statin was associated with a reduced need for retinal laser treatment with a hazard ratio of 0.70 (0.64, 0.76) (p < 0.001; I2: 0%), intravitreal injection with a hazard ratio of 0.82 (0.79, 0.85) (p < 0.001; I2: 0%), and vitrectomy with a hazard ratio of 0.64 (0.48, 0.85) (p < 0.001; I2: 75%). Overall, statin was associated with a reduced need for intervention for diabetic retinopathy with a hazard ratio of 0.72 (0.64, 0.80) (p < 0.001; I2: 73%). The regression-based Egger’s test showed statistically significant small-study effects for non-proliferative diabetic retinopathy (p = 0.011) outcomes. Conclusion: Statin was associated with a decreased risk of diabetic retinopathy and its subtypes. Statin also reduced the need for intervention with retinal laser treatment, intravitreal injection, and vitrectomy.
Relationships between psychosocial stressors among pregnant women in San Francisco: A path analysis

Pregnant women who experience psychosocial stressors, such as stressful life events, poor neighborhood quality, and financial hardship, are at an increased risk for adverse pregnancy outcomes. Yet, few studies have examined associations between multiple stressors from different sources, which may be helpful to better inform causal pathways leading to adverse birth outcomes. Using path analysis, we examined associations between multiple self-reported stressor exposures during and before pregnancy in the Chemicals in Our Bodies-2 study (N = 510), a demographically diverse cohort of pregnant women in San Francisco. We examined associations between eight self-reported exposures to stressors and three responses to stress which were assessed via interview questionnaire at the 2nd trimester. Stressors included: neighborhood quality, stressful life events, caregiving, discrimination, financial strain, job strain, food insecurity, and unplanned pregnancy. Perceived stress, depression, and perceived community status were included as indicators of self-reported stress response. Our model indicated that women who experienced discrimination and food insecurity had a 3.76 (95% confidence interval [CI] = 1.60, 5.85) and 2.67 (95% CI = 1.31, 4.04) increase in depression scale scores compared to women who did not experience discrimination and food insecurity, respectively. We additionally identified job strain and caregiving for an ill family member as strong predictors of increased depressive symptoms (β = 1.63, 95% CI = 0.29, 3.07; β = 1.48, 95% CI = 0.19, 2.70, respectively). Discrimination, food insecurity, and job strain also influenced depression indirectly through the mediating pathway of increasing perceived stress, although indirect effects were less precise. In our study population, women who experienced discrimination, food insecurity, job strain and caregiving for an ill family member had an increased number of depressive symptoms compared to women who did not experience these stressors. Results from our study highlight the complex relationships between stressors and stress responses and may help to identify possible mediating pathways leading to adverse pregnancy outcomes.
Neural networks of different species, brain areas and states can be characterized by the probability polling state

Cortical networks are complex systems of a great many interconnected neurons that operate from collective dynamical states. To understand how cortical neural networks function, it is important to identify their common dynamical operating states from the probabilistic viewpoint. Probabilistic characteristics of these operating states often underlie network functions. Here, using multi‐electrode data from three separate experiments, we identify and characterize a cortical operating state (the “probability polling” or “p‐polling” state), common across mouse and monkey with different behaviors. If the interaction among neurons is weak, the p‐polling state provides a quantitative understanding of how the high dimensional probability distribution of firing patterns can be obtained by the low‐order maximum entropy formulation, effectively utilizing a low dimensional stimulus‐coding structure. These results show evidence for generality of the p‐polling state and in certain situations its advantage of providing a mathematical validation for the low‐order maximum entropy principle as a coding strategy.
Papular‐purpuric exanthem in a COVID‐19 patient: clinical and dermoscopic description

Acute Coronavirus disease 2019 (COVID-19) has become a global health concern associated with a broad spectrum of clinical presentations. Cutaneous lesions in COVID-19 are still under continuous study. We report a case of COVID-19 (+) patient with late-onset cutaneous rash associated with a systemic inflammatory response during the second hospitalization.
Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-β1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.
Tonic GABA‐activated synaptic and extrasynaptic currents in dentate gyrus granule cells and CA3 pyramidal neurons along the mouse hippocampal dorsoventral axis

The hippocampus is a medial temporal lobe structure in the brain and is widely studied for its role in memory and learning, in particular, spacial memory and emotional responses. It was thought to be a homogenous structure but emerging evidence shows differentiation along the dorsoventral axis and even microdomains for functional and cellular markers. We have examined in two cell‐types of the hippocampal projection neurons, the dentate gyrus (DG) granule cells and CA3 pyramidal neurons, if the GABA‐activated tonic current density varied between the dorsal (septal) and the ventral (temporal) poles of the male mouse hippocampus. Tonic synaptic currents, arising from spontaneous and miniature inhibitory postsynaptic currents (sIPSC, mIPSC), and extrasynaptic tonic currents were evaluated. The results revealed different levels of sIPSC but not mIPSC density between the dorsal and ventral hippocampal neurons for both the DG granule cells and the CA3 pyramidal neurons. The extrasynaptic tonic current density was larger in the DG granule cells as compared to the CA3 pyramidal neurons but did not vary between the dorsal and ventral regions. IPSC bursting was observed in both cell‐types in the ventral hippocampus but was more common in the CA3 pyramidal neurons. Only in the dorsal DG granule cells was the level of the sIPSC and mIPSC density similar. The results indicate that the tonic GABAergic inhibition is particularly strong in the ventral hippocampal DG granule cells and enhanced in the dorsal as compared to the ventral hippocampal CA3 pyramidal neurons.
Overexpression of a Maize SPS Gene Improves Yield Characters of Potato under Field Conditions

Abstract We analyzed the yield characters of field-grown transgenic potato plants (Solanum tuberosum) carrying a maize gene for sucrose-phosphate synthase (SPS), the key enzyme in sucrose synthesis. The SPS activity in the leaves of transgenic plants (line Ag1203) was 2 times that of the control (cv. May Queen). There was no difference in the photosynthetic CO2 uptake rates between Ag1203 and May Queen plants, and the leaf starch content of Ag1203 was lower. These observations indicate that the introduction of a foreign SPS gene improved the supply of photosynthate from source (leaves) to sink (tubers). Additionally, leaf senescence of the transgenic potato plants was delayed relative to that of May Queen. The average tuber weight and total yield of Ag1203 plants were at least 20% higher, and the tuber sucrose content, which is related to eating quality, was also higher. Increased translocation of photosynthate and longer period of photosynthetic activity in the leaves may have increased the yield of Ag1203. These results suggest that introduction of the SPS gene improved the yield characters and quality of potato tubers under field conditions.
High dropout rate from maternity continuum of care after antenatal care booking and its associated factors among reproductive age women in Ethiopia, Evidence from Demographic and Health Survey 2016

Background Maternal continuums of care were vital to reducing maternal and neonatal mortalities. While the dropout rate remains high and limited studies were found on risk factors associated with a high dropout rate of the maternal continuum of care. Objective This study aimed to assess the magnitude of dropout rate and its associated factors of maternity continuum of care in Ethiopia, 2016 Methods An in-depth secondary data analysis was conducted from the Ethiopian Demographic and Health Survey 2016 data. A total of 4,693 women who were booked for antenatal care visit were included to the final analysis. A community-based cross-sectional study design and a pre-tested and standardized questionnaire were used to collect the survey data. Data were weighted using women data weighting variables. Chi-square and multicollinearity assumptions were checked for independent variables. Bi-variable and multivariable logistics regression used to identify associated factors with a cut of the p-value of 0.2 and 0.05 respectively. Adjusted Odds Ratio (AOR) with 95%CI was reported for the final model. Results Of the total 4,693 women who were booked for antenatal care visits, 2,092(44.58%), 2,183 (46.52%), and 4,086(87.07%) dropped from a recommended number of ANC, Institutional delivery and postnatal care visit respectively. Only 308 (6.56%, 95%CI: 5.89, 7.31) women used all the complete continuum of care. Not married, and poorest wealth index were significantly associated with dropout from ANC visit. Being a protestant religious follower was significantly associated with dropout from PNC after antenatal care booking. While not exposed to media, distance from health facility as a big problem, protestant affiliation, parity of 2 to 4 and above4, Wealth index of the poorest, poorer, middle, and richer significantly associated with dropout from institutional delivery. Not being informed about pregnancy complications during their ANC visit was significantly associated with dropout from ANC, PNC, and institutional delivery. Conclusions Dropout of women from the maternity continuum of care after antenatal care booking was a public health problem in Ethiopia. Socio-demographic, pregnancy, and health service-related factors were significant determinants of dropout from the maternity continuum of care. Improving the family wealth index, increasing access to health facilities, media exposure, and giving more information during the antenatal care visit is important to reduce the dropout rate from the maternity continuum of care.
Overexpression of Nicotinamide phosphoribosyltransferase in mouse cells confers protective effect against oxidative and ER stress-induced premature senescence.

A main feature of aged organisms is the accumulation of senescent cells. Accumulated senescent cells, especially stress-induced premature senescent cells, in aged organisms lead to the decline of the regenerative potential and function of tissues. We recently reported that the overexpression of NAMPT, which is the rate-limiting enzyme in mammalian NAD+ salvage pathway, delays replicative senescence in vitro. However, whether Nampt-overexpressing cells are tolerant of stress-induced premature senescence remains unknown. Here, we show that primary mouse embryonic fibroblasts derived from Nampt-overexpressing transgenic mice (Nampt Tg-MEF cells) possess resistance against stress-induced premature senescence in vitro. We found that higher oxidative or endoplasmic reticulum (ER) stress is required to induce premature senescence in Nampt Tg-MEF cells compared to wild type cells. Moreover, we found that Nampt Tg-MEF cells show acute expression of unfolded protein response (UPR) related genes, which in turn would have helped to restore proteostasis and avoid cellular senescence. Our results demonstrate that NAMPT/NAD+ axis functions to protect cells not only from replicative senescence, but also from stress-induced premature senescence in vitro. We anticipate that in vivo activation of NAMPT activity or increment of NAD+ would protect tissues from the accumulation of premature senescent cells, thereby maintaining healthy aging.
Pharmacologic Treatments for Irritable Bowel Syndrome: an Umbrella Systematic Review.

BACKGROUND AND AIMS Multiple pharmacologic treatments are available for the management of irritable bowel syndrome (IBS), and a large body of evidence has been presented. However, the strength and credibility of the evidence have not been comprehensively evaluated. We aimed to review the systematic reviews and meta- analyses of pharmacologic treatments for IBS and evaluate the credibility of the findings. METHODS We searched MEDLINE, Embase, and Cochrane library from inception to September 2019 for systematic reviews evaluating the effectiveness of pharmacologic treatments for IBS. We summarized relative ratios (RR), evaluated the credibility of the evidence and classified the evidence into convincing, highly suggestive, suggestive, and weak. RESULTS We included 11 systematic reviews with 40 meta-analyses (330 randomized controlled trials and 86,459 participants) assessing 10 treatment categories and 2 drugs. Most of the pharmacologic treatments were significantly superior over placebo as reported by the included meta-analyses. The evidence for 5-hydroxytryptamine (5-HT)3 antagonists (RR=1.56, 95%CI: 1.43-1.71), antispasmodics (RR=1.19, 95%CI: 1.02-1.39), and alosetron (RR=1.46, 95%CI: 1.26-1.71) were highly suggestive for relieving global IBS symptoms. 5-HT4 agonists (RR= 1.26, 95%CI: 1.19-1.34) and guanylate cyclase-C (GCC) agonists (RR=1.73, 95%CI: 1.54-1.95) were found to give convincing evidence for the improvement of the responder rate. 5-HT3 antagonists (RR=1.32, 95%CI: 1.26-1.38) offered convincing evidence for relieving abdominal pain. CONCLUSIONS Evidence for 5-HT3 antagonists, 5-HT4 agonists and GCC agonists, antispasmodics, and alosetron were suggestive for the treatment of IBS. However, owing to the risk of bias in randomization methods, the results for GCC should be interpreted with caution.
Double-Hit–Induced Leukocyte Extravasation Driven by Endothelial Adherens Junction Destabilization

Key Points Synergic effects of LPS and histamine induce jagged junction morphology. Junction morphology drives TEM separately from adhesion molecules or WPBs. S1P and Rap1 signaling pathways reverse jagged junction morphology. During inflammation, endothelial cells are bombarded with cytokines and other stimuli from surrounding cells. Leukocyte extravasation and vascular leakage are both prominent but believed to be uncoupled as they occur in separate spatiotemporal patterns. In this study, we investigated a “double-hit” approach on primary human endothelial cells primed with LPS followed by histamine. Using neutrophil transendothelial migration (TEM) under physiological flow assays, we found that an LPS-primed endothelium synergistically enhanced neutrophil TEM when additionally treated with histamine, whereas the effects on neutrophil TEM of the individual stimuli were moderate to undetectable. Interestingly, the double-hit–induced TEM increase was not due to decreased endothelial barrier, increased adhesion molecule expression, or Weibel–Palade body release. Instead, we found that it was directly correlated with junctional remodeling. Compounds that increased junctional “linearity” (i.e., stability) counteracted the double-hit effect on neutrophil TEM. We conclude that a compound, in this case histamine (which has a short primary effect on vascular permeability), can have severe secondary effects on neutrophil TEM in combination with an inflammatory stimulus. This effect is due to synergic modifications of the endothelial cytoskeleton and junctional remodeling. Therefore, we hypothesize that junctional linearity is a better and more predictive readout than endothelial resistance for compounds aiming to attenuate inflammation.