Miracle-dz/UniFAR-FTUs huggingface dataset:
Fabrication of Fine Puerarin Nanocrystals by Box–Behnken Design to Enhance Intestinal Absorption

Puerarin is widely used as a therapeutic agent to cardiovascular diseases in clinics in China through intravenous administration, which could elicit adverse drug reactions caused by cosolvents, hindering its application in clinics. Therefore, the development of oral dosage is urgently needed. In our previous studies, we proved that the bioavailability of puerarin increased as particle sizes of nanocrystals decreased; however, we have not optimized the best process parameters for nanocrystals. In this study, we aim to fabricate fine nanocrystals (with smallest particle size) by Box–Behnken design and study the intestinal permeability of puerarin and its nanocrystals via employing everted gut sac model and in situ perfusion model. The results showed that the Box–Behnken design could be used to optimize the producing parameters of puerarin nanocrystals, and the particle sizes of fine nanocrystals were about 20 nm. Results of everted gut sacs showed that the polyvinylpyrrolidone (PVP) and verapamil had no influence on the absorption of puerarin and nanocrystals, and the nanocrystals could increase the Papp of puerarin for 2.2-, 2.9-, and 2.9-folds, respectively, in duodenum, jejunum, and ileum. Enhanced Ka and Peff were observed on the nanocrystal group, compared with puerarin, and PVP and verapamil had no influence on the absorption of nanocrystals, while the absorption of puerarin was influenced by P-gp efflux. Combining the results mentioned above, we can conclude that the Box–Behnken design benefits the optimization for preparation of nanocrystals, and the nanocrystals could enhance the intestinal absorption of puerarin by enhanced permeability and inhibited P-gp efflux.
Circadian rhythms in the absence of the clock gene Bmal1

Redundancy in circadian clocks? The transcription factor BMAL1 is a core component of the mammalian circadian clock; without it, circadian behaviors are abolished. However, Ray et al. found that in animals lacking BMAL1, peripheral tissues synchronized with a brief pulse of the glucocorticoid hormone dexamethasone appear to retain a 24-hour pacemaker that sustains rhythmic gene expression, protein abundance, and protein phosphorylation in excised liver cells and fibroblasts (see the Perspective by Brown and Sato). These oscillations persisted in the absence of cues from changes in light or temperature. The results raise intriguing questions about the possible nature of the oscillator that maintains the observed rhythms. Science, this issue p. 800; see also p. 740 Mouse liver and fibroblast cells retain 24-hour biochemical oscillations without a key circadian clock component. Circadian (~24 hour) clocks have a fundamental role in regulating daily physiology. The transcription factor BMAL1 is a principal driver of a molecular clock in mammals. Bmal1 deletion abolishes 24-hour activity patterning, one measure of clock output. We determined whether Bmal1 function is necessary for daily molecular oscillations in skin fibroblasts and liver slices. Unexpectedly, in Bmal1 knockout mice, both tissues exhibited 24-hour oscillations of the transcriptome, proteome, and phosphoproteome over 2 to 3 days in the absence of any exogenous drivers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. We suggest that such oscillations might be underpinned by transcriptional regulation by the recruitment of ETS family transcription factors, and nontranscriptionally by co-opting redox oscillations.
Crossing thresholds on the way to ecosystem shifts

Meshing evidence from multiple datasets unveils Earth's mechanisms for adapting to environmental changes As the Earth system moves through continuous changes, scientists have attempted to predict pathways the planet will follow by unraveling trajectories of individual ecosystems and their interactions and by identifying the thresholds beyond which irreversible changes might occur (1). For example, increases in global aridity are known to affect terrestrial ecosystems, but it remains unknown whether modifications in global aridity will cause gradual or abrupt systemic or idiosyncratic transitions. Now, on page 787 of this issue, Berdugo et al. (2) analyze large datasets of observational and empirical evidence from studies of drylands. The authors show that changes occur in a sequential series of nonlinear thresholds beyond which dryland vegetation can vanish, leaving bare soil to prevail.
Molybdenum Disulfide Nanosheets Aligned Vertically on Carbonized Silk Fabric as Smart Textile for Wearable Pressure Sensing and Energy Devices.

Flexible electronics have gained considerable research concern due to their wide prospect for health monitoring, soft robotics and artificial intelligence, wherein flexible pressure sensors are necessary components of wearable devices. It is well known that the synergistic functions and multiscale structures of hybrid materials exert tremendous effects on the performance of flexible devices. Herein, inspired by the unique structure of the faceplate of sunflowers, we construct a hierarchical structure by in-situ grown vertically aligned molybdenum disulfide (MoS2) nanosheets on carbonized silk fabric (MoS2/CSilk), which is applied as the sensing material in flexible pressure sensors. The MoS2/CSilk pressure sen-sor showed high sensitivity and good stability. We demonstrated its applications in monitoring subtle physiology sig-nals, such as pulse wave and voice vibrations. In addition, they were used as electrodes in lithium ion batteries. The MoS2/CSilk electrode delivered ultra-high first-cycle discharge and charge capacities of 2895 and 1594 mA h g-1. The MoS2/CSilk electrode exhibited a high capacity of 810 mA h g-1 with a CE approaching 100% even after 300 cycles, sug-gesting a good high-rate stability. The excellent overall performances are attributed to the unique structure the MoS2/CSilk and the synergistic effect of CSilk and MoS2. The concept and strategy of this work can be extended to the design and fabrication of other multifunctional devices.
Lidocaine vs. Other Local Anesthetics in the Development of Transient Neurologic Symptoms (TNS) Following Spinal Anesthesia: A Meta-Analysis of Randomized Controlled Trials

The use of lidocaine in spinal anesthesia may increase the risk of transient neurological symptoms (TNS) according to previous meta-analyses. However, the previous meta-analyses lacked data on some other local anesthetics and thus, more evaluations are still needed to compare the effect of lidocaine on the development of TNS. The objective of this study was to compare the risk of TNS according to lidocaine versus other local anesthetics in patients undergoing spinal anesthesia. A total of 39 randomized controlled trials with 4733 patients were analyzed. The incidence of TNS was 10.8% in the lidocaine group and was 2.2% in the control groups (risk ratio (RR) 4.12, 95% confidence interval (CI) 3.13 to 5.43, p < 0.001). In subgroup analysis, lidocaine increased the incidence of TNS compared with other local anesthetics except mepivacaine, ropivacaine or sameridine. The risk of TNS was higher in the hyperbaric (p < 0.001) or isobaric lidocaine (p < 0.001) group compared with the control group, but there were no differences found between the two groups when hypobaric lidocaine was administered (p = 1.00). This study confirmed that lidocaine for spinal anesthesia still causes TNS more frequently than most other local anesthetics, especially when hyperbaric or isobaric lidocaine was used.
Effects of Assistance During Early Stance Phase Using a Robotic Knee Orthosis on Energetics, Muscle Activity, and Joint Mechanics During Incline and Decline Walking

The knee joint performs a significant amount of positive or negative mechanical work during gradient walking, and targeted assistance during periods of high mechanical work could yield strong human augmentation benefits. This paper explores the biomechanical effects of providing knee extension assistance during the early stance phase of the gait cycle using a powered unilateral knee exoskeleton during gradient walking on able-bodied subjects. Twelve subjects walked on 15% gradient incline and decline surfaces with the exoskeleton providing knee extension assistance during the early stance phase of the gait cycle. For both incline and decline walking, the exoskeleton assistance reduced the muscle activation of the knee extensors on the assisted leg ( ${p}< {0.05}$ ). However, only approximately half the individuals responded to exoskeleton assistance positively by reducing their metabolic cost of walking for both incline and decline tasks. The results indicate that, unlike the individuals who did respond, the individuals who did not respond to the assistance may have penalized their metabolic cost by their biomechanical compensatory behaviors from the unassisted leg.
Corneal pulsation and biomechanics during induced ocular pulse. An ex-vivo pilot study

The purpose of this study was to ascertain the relationships between the amplitude of the corneal pulse (CP) signal and the parameters of corneal biomechanics during ex-vivo intraocular pressure (IOP) elevation experiments on porcine eyes with artificially induced ocular pulse cycles. Two experiments were carried out using porcine eyes. In the first one, a selected eye globe was subjected to three IOP levels (15, 30 and 45 mmHg), where changes in physical ocular pulse amplitude were controlled by infusion/withdrawal volumes (ΔV). In the second experiment, six eyes were subjected to IOP from 15 mmHg to 45 mmHg in steps of 5 mmHg with a constant ΔV, where corneal deformation parameters were measured using Corvis ST. In both experiments, at each IOP, the CP and IOP signals were acquired synchronically using a non-contact ultrasonic distance sensor and a pressure transmitter, respectively. Based on the amplitudes of the CP and IOP signals ocular pulse based corneal rigidity index (OPCRI) was calculated. Results indicate positive correlations between ΔV and the physical ocular pulse amplitude, and between ΔV and the corneal pulse amplitude (both p < 0.001). OPCRI was found to increase with elevated IOP. Furthermore, IOP statistically significantly differentiated changes in OPCRI, the amplitudes of CP and IOP signals and in most of the corneal deformation parameters (p < 0.05). The partial correlation analysis, with IOP as a control variable, revealed a significant correlation between the length of the flattened cornea during the first applanation (A1L) and the corneal pulse amplitude (p = 0.002), and between A1L and OPCRI (p = 0.003). In conclusion, this study proved that natural corneal pulsations, detected with a non-contact ultrasonic technique, reflect pressure-volume dynamics and can potentially be utilized to assess stiffness of the cornea. The proposed new rigidity index could be a simple approach to estimating corneal rigidity.
Beyond Band-Aids for Bullet Holes: Firearm Violence As a Public Health Priority

Objectives: To review the public health approach to preventing and treating firearm violence. Data Sources: Peer-reviewed, published scholarship and federal data systems. Study Selection: English-language, indexed research articles on the epidemiology, risk, prevention, and consequences of firearm violence. Data Extraction: This narrative review includes findings related to the epidemiology and impact of firearm violence, focusing on short- and long-term outcomes. Evidence supporting interventions at the individual, agent, and environmental level to reduce firearm-related harm was examined. Data Synthesis: Firearm violence is a major public health challenge in the Unites States. The consequences of firearm violence reach beyond the nearly 40,000 firearm-related deaths and 90,000 firearm-related injuries each year. Firearm violence, including self-harm, assault, and unintentional injury, affects the health of individuals, families, communities, and health systems. Data sources remain inadequate, however, to fully capture these impacts. Treating firearm violence as a disease and taking a public health approach to prevention and treatment is key to reducing the harms of firearm violence. Using a public health framework not only recognizes the physical and mental consequences of firearm violence but also focuses our attention on underlying causes and on innovative, multi-level interventions to reduce the harms of firearm violence. Conclusions: The public health approach positions clinicians to change the conversation from political diatribe of pro-gun and anti-gun to systematically reducing injury and death. To achieve comparable success, we must design, test, and implement effective interventions at the environmental, policy, technological, and individual levels to prevent firearm violence. We must collect robust data on firearm violence and its consequences. And we must reckon with the conditions of inequality and disadvantage that feed violence through all means.
T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives

Fibromyalgia is one of the most important “rheumatic” disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1β, IL-6, and TNFα. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia.
Effect of pregravid obesity on perinatal outcomes in singleton pregnancies following in vitro fertilization and the weight-loss goals to reduce the risks of poor pregnancy outcomes: A retrospective cohort study

Objective In the present study, we aimed to determine whether pregravid obesity independently predicts increased risks of perinatal complications following in vitro fertilization (IVF) and the weight loss goals to reduce the risk of poor pregnancy outcomes. Design Retrospective cohort study. Population All pregnancies after first the fresh IVF cycle from January 2014 to December 2016 in the Reproductive Center affiliated to Shandong University were reviewed. A total of 3,962 eligible singleton births were stratified into cohorts based on the body mass index (BMI) definitions of the Working Group on Obesity in China (WGOC). Main outcome measures Adverse perinatal outcomes. Results Pregravid overweight and obesity were associated with increased risks of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), including gestational hypertension (GH) and pre-eclampsia (PE), polyhydramnios, preterm premature rupture of the membranes (PPROM), placental abruption, preterm birth (PTB) <37 weeks, caesarean section (CS), fetal macrosomia, large for gestational age (LGA) >90th percentile, neonatal respiratory distress syndrome (NRDS), neonatal intensive care unit (NICU) admission and congenital anomalies as compared with the normal-weight group after adjustment of differences in age, parity, polycystic ovary syndrome (PCOS) and type of controlled ovarian hyperstimulation (COH). The increased risks of PPROM, NRDS and congenital anomalies were eliminated after adjustment of GDM development, whereas the increased risk of NRDS disappeared after adjustment of HDP. Placenta previa was not significantly different between the obese group and reference group (REF). Moreover, the rates of postpartum hemorrhage (PPH), PTB<32 weeks, small for gestational age (SGA) >90th percentile and perinatal mortality were also not significantly different between above-mentioned two groups. For obese women, a 10%-15% reduction in prepregnancy BMI was associated with significantly decreased risks of GH, CS and fetal macrosomia. For overweight women, just a 5% reduction in BMI could significantly reduce the risks of GDM, CS and fetal macrosomia. Conclusions Pregravid obesity could independently predict a higher risk of adverse pregnancy outcomes after adjustment of differences in maternal age, parity, PCOS, and type of COH in IVF pregnancies. The potential mechanism that obesity potentiated the risks of some poor perinantal outcomes might occur through the development of GDM and HDP. A 10%-15% reduction in pregravid BMI for obese women and a 5% reduction for overweight women were associated with a significant reduction of poor perinatal complications.
Protective Effect of l-Hexaguluroic Acid Hexasodium Salt on UVA-Induced Photo-Aging in HaCaT Cells

This study aimed to show the α-l-Hexaguluroic acid hexasodium salt (G6) protective effect against UVA-induced photoaging of human keratinocyte cells. We found that G6 localized to the mitochondria and improved mitochondrial functions. G6 increased respiratory chain complex activities, which led to increased cellular ATP content and NAD+/NADH ratio. Thus, G6 alleviated the oxidative stress state in UVA-irradiated cells. Moreover, G6 can regulate the SIRT1/pGC-1α pathway, which enhanced the cells’ viability and mitochondria energy metabolism. Notably, the anti-photoaging potential of G6 was directly associated with the increased level of MMP and SIRT1, which was followed by the upregulation of pGC-1α, D-LOOP, and Mt-TFA, and with the transcriptional activation of NRF1/NRF2. Taking all of the results together, we conclude that G6 could protect HaCaT cells from UVA-induced photo-aging via the regulation of mitochondria energy metabolism and its downstream signaling pathways.
Electron‐State Confinement of Polysulfides for Highly Stable Sodium–Sulfur Batteries

Confinement of polysulfides in sulfur cathodes is pivotal for eliminating the “shuttle effect” in metal–sulfur batteries, which represent promising solutions for large‐scale and sustainable energy storage. However, mechanistic exploration and in‐depth understanding for the confinement of polysulfides remain limited. Consequently, it is a critical challenge to achieve highly stable metal–sulfur batteries. Here, based on a 2D metal–organic framework (2D MOF), a new mechanism to realize effective confinement of polysulfides is proposed. A combination of in situ synchrotron X‐ray diffraction, electrochemical measurements, and theoretical computations reveal that the dynamic electron states of the Ni centers in the 2D MOF enable the interaction between polysulfides and the MOF in the discharge/charge process to be tuned, resulting in both strong adsorption and fast conversion kinetics of polysulfides. The resultant room‐temperature sodium–sulfur batteries are amongst the most stable reported so far, thus demonstrating that the new mechanism opens a promising avenue for the development of high‐performance metal–sulfur batteries.
Association of the Triglyceride to High-Density Lipoprotein Ratio and the Visceral Adiposity Index with Metabolic Syndrome in Diabetic Susceptible Population

Abstract The aim of this study was to explore the association of the triglyceride to high-density lipoprotein ratio (TG/HDL) and the visceral adiposity index (VAI) with metabolic syndrome (Mets) in high-risk populations of diabetic patients. Patients were recruited from the Endocrinology Clinic of Hebei General Hospital from April 2018 to April 2019,according to the “Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2017 Edition)”. A total of 824 patients participated in the study. The association between TG/HDL or VAI and Mets in these patients was assessed using a multivariate logistic regression model. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TG/HDL and VAI to predict Mets in the diabetic susceptible population. The prevalence of Mets gradually increased in males and females with advancing tertiles of TG/HDL or VAI. After adjusting for the relevant risk factors, TG/HDL and VAI were positively correlated with Mets in men and women. Both of them showed a better the area under the ROC curve (AUC) for Mets in females than body mass index, waist circumference, TG and homeostatic model assessment of insulin resistance. In females, the cut-off point of 1.67 for VAI showed a higher accuracy for Mets (sensitivity 0.756, specificity 0.705, Youden index 0.461), the same relationship not significant in men. TG/HDL and VAI provide a high predictive value for Mets in a diabetic susceptible population, especially in females.
The Impact of Hypoxia on Neutrophil Degranulation and Consequences for the Host

Neutrophils are key effector cells of innate immunity, rapidly recruited to defend the host against invading pathogens. Neutrophils may kill pathogens intracellularly, following phagocytosis, or extracellularly, by degranulation and the release of neutrophil extracellular traps; all of these microbicidal strategies require the deployment of cytotoxic proteins and proteases, packaged during neutrophil development within cytoplasmic granules. Neutrophils operate in infected and inflamed tissues, which can be profoundly hypoxic. Neutrophilic infiltration of hypoxic tissues characterises a myriad of acute and chronic infectious and inflammatory diseases, and as well as potentially protecting the host from pathogens, neutrophil granule products have been implicated in causing collateral tissue damage in these scenarios. This review discusses the evidence for the enhanced secretion of destructive neutrophil granule contents observed in hypoxic environments and the potential mechanisms for this heightened granule exocytosis, highlighting implications for the host. Understanding the dichotomy of the beneficial and detrimental consequences of neutrophil degranulation in hypoxic environments is crucial to inform potential neutrophil-directed therapeutics in order to limit persistent, excessive, or inappropriate inflammation.