Miracle-dz/UniFAR-FTUs huggingface dataset:
A Retrospective Study of Rare Listeria Meningoencephalitis in Immunocompetent Children in China

Objectives Listeria meningoencephalitis (LMM) is very rare in healthy children. We aimed to assess the clinical features, differential diagnosis, treatment options, and outcomes of LMM in immunocompetent children through a retrospective study. Methods The clinical symptoms, laboratory findings, imaging features, antibiotic use, and metagenomic next-generation sequencing (mNGS) results of the cerebrospinal fluid (CSF) were obtained from immunocompetent children who were diagnosed with LMM and admitted to the Xi'an Children's Hospital from May 2018 to July 2020. Results The data from 8 immunocompetent children were retrospectively analyzed in this study. The cohort included data from 5 males and 3 females who were aged from 1 year and 7 months to 16 years and 6 months. A total of 4 patients had chilled food before onset. The complications included hyponatremia (3/8), hydrocephalus (2/8), and hemophagocytic syndrome (1/8). In total, 8 patients were diagnosed with Listeria monocytogenes by positive CSF culture or mNGS results. The positive rate of CSF culture was 62.5% (5/8). A total of 5 patients conducted CSF mNGS, and the results of the mNGS were positive in 4 patients (80%, 4/5) and suspected in 1 patient. A total of 7 patients changed their therapeutic regimen to combined antibacterial therapies that included linezolid and meropenem (5/8), or ampicillin and meropenem (2/8). A total of 5 patients had favorable outcomes (Glasgow Outcome Scale, GOSE = 5) while two patients had unfavorable outcomes (GOSE = 1) and were complicated with hyponatremia and hydrocephalus. Conclusions Listeria meningoencephalitis (LMM) can occur in children with normal immune function and is commonly mistaken for other central nervous system infections. L. monocytogenes can be quickly and accurately detected by mNGS. Hyponatremia and hydrocephalus may indicate unfavorable outcomes.
Rewiring the Metabolic Network to Increase Docosahexaenoic Acid Productivity in Crypthecodinium cohnii by Fermentation Supernatant-Based Adaptive Laboratory Evolution

Docosahexaenoic acid (DHA, 22:6n-3) plays significant roles in enhancing human health and preventing human diseases. The heterotrophic marine dinoflagellate Crypthecodinium cohnii is a good candidate to produce high-quality DHA. To overcome the inhibition caused by the fermentation supernatant in the late fermentation stage of DHA-producing C. cohnii, fermentation supernatant-based adaptive laboratory evolution (FS-ALE) was conducted. The cell growth and DHA productivity of the evolved strain (FS280) obtained after 280 adaptive cycles corresponding to 840 days of evolution were increased by 161.87 and 311.23%, respectively, at 72 h under stress conditions and increased by 19.87 and 51.79% without any stress compared with the starting strain, demonstrating the effectiveness of FS-ALE. In addition, a comparative proteomic analysis identified 11,106 proteins and 910 differentially expressed proteins, including six stress-responsive proteins, as well as the up- and downregulated pathways in FS280 that might contribute to its improved cell growth and DHA accumulation. Our study demonstrated that FS-ALE could be a valuable solution to relieve the inhibition of the fermentation supernatant at the late stage of normal fermentation of heterotrophic microalgae.
Mercury and Mercury-Containing Preparations: History of Use, Clinical Applications, Pharmacology, Toxicology, and Pharmacokinetics in Traditional Chinese Medicine

Historically, mercury and mercury-containing preparations have been widely used in traditional Chinese medicine and applied in many clinical practices mainly in the form of mercury sulfides. The clinical application, toxicity manifestations, and symptoms of these preparations largely depend on the route of administration and the dosage form. Commonly used mercury-containing medicinal materials and preparations in traditional Chinese medicine include Cinnabar, an excellent medicine for tranquilizing the nerves; Hongsheng Dan and Baijiang Dan, which have antibacterial, anti-inflammatory, promotion of tissue repair and regeneration and other pharmacological effects. Tibetan medicine commonly uses Zaotai and Qishiwei Zhenzhu pills, which have pharmacological effects such as sedation, anti-inflammatory, anti-convulsant, and improvement of cerebral apoplexy. Menggen Wusu Shibawei pills, commonly used in Mongolian traditional medicine, have the muscle growth and astringent effects. In India and Europe, mercury is often used for treating syphilis. This article summarizes the history, clinical application, pharmacology, toxicology, and pharmacokinetics of mercury and mercury-containing preparations in traditional medicines. In terms of clinical application, it provides suggestions for the rational use and safety of mercury-containing drugs in clinical practices and in public health issues. It will further provide a reference for formulation strategies related to mercury risk assessment and management.
Succinate Is a Natural Suppressor of Antiviral Immune Response by Targeting MAVS

Succinate is at the crossroads of multiple metabolic pathways and plays a role in several immune responses acting as an inflammation signal. However, whether succinate regulates antiviral immune response remains unclear. Here, we found that the production of succinate was reduced in RAW264.7 cells during vesicular stomatitis virus (VSV) infection. Using diethyl succinate to pretreat the mouse peritoneal macrophages and RAW264.7 cells before VSV infection, the production of interferon-β (IFN-β), chemokine (C–X–C motif) ligand 10 (CXCL-10), and IFN-stimulated genes 15 (ISG15) was significantly decreased, following which the VSV replication in diethyl succinate-pretreated cells was obviously increased. Moreover, succinate decreased the expression of IFN-β in serum, lung, and spleen derived from the VSV-infected mice. The overall survival rate in the VSV-infected mice with diethyl succinate pretreatment was also remarkably downregulated. Furthermore, we identified that succinate inhibited the activation of MAVS-TBK1-IRF3 signaling by suppressing the formation of MAVS aggregates. Our findings provide previously unrecognized roles of succinate in antiviral immune response and establish a novel link between metabolism and innate immune response.
Corticosteroid Treatment Prevents Lipopolysaccharide-Induced Increase of ACE2 and Reduces Fibrin Degradation Products in Bronchoalveolar Lavage Fluid

The assessment of systemic corticosteroid effects on intrapulmonary disease biomarkers is challenging. This retrospective evaluation of a human endotoxemia model quantified ACE2 and fibrin degradation product (FDP) concentrations in bronchoalveolar lavage fluid (BALF) samples from a randomized, double-blind, placebo-controlled study (NCT01714427). Twenty-four healthy volunteers received either 2 × 40 mg intravenous dexamethasone or placebo. These doses were administered 12 h apart prior to bronchoscopy-guided intrabronchial lipopolysaccharide (LPS) stimulation (control: saline into the contralateral lung segment). We quantified ACE2 concentration, the Angiotensin-II-to-Angiotensin-1-7 conversion rate as well as FDP in BALF 6 h after LPS instillation. In placebo-treated subjects, LPS instillation increased ACE2 concentrations compared to unstimulated lung segments [1,481 (IQR: 736–1,965) vs. 546 (413–988) pg/mL; p = 0.016]. Dexamethasone abolished the increase in ACE2 concentrations (p=0.13). Accordingly, LPS instillation increased the Angiotensin-II-to-Angiotensin-1-7 conversion capacity significantly in the placebo cohort, indicating increased enzymatic activity (p = 0.012). FDP increased following LPS-instillation [8.9 (2.7–12.2) vs. 6.6 (0.9–9.6) ng/mL, p = 0.025] in the placebo group, while dexamethasone caused a shut-down of fibrinolysis in both lung segments. LPS instillation increased ACE2 concentration, its enzymatic activity and FDP, which was mitigated by systemic dexamethasone treatment. Our results strengthen previously published findings regarding the efficiency of corticosteroids for the treatment of COVID-19-induced acute lung injury.
Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia

Background Hypoxic-ischemic encephalopathy (HIE) occurs when an infant’s brain has not received adequate oxygen and blood supply, resulting in ischemic and hypoxic damage. Currently, supportive care and hypothermia therapy have been the standard treatment for HIE. However, there are still over 20% of treated infants died and 19–30% survived with significant disability. HIE animal model was first established by Rice et al., involving the ligation of one common carotid artery followed by hypoxia. In this study, we investigated human umbilical cord blood (HUCB) and its two components mononuclear cell (MNC) and red cell fraction (RCF) in both short and long term study using a modified HIE rat model. Methods In this modified HIE model, both common carotid arteries were occluded, breathing 8% oxygen in a hypoxic chamber for 60-min, followed by the release of the common carotid arteries ligature, mimicking reperfusion injury. For cell therapeutic study, cells were intravenously injected to HIE rat pups, and both behavioral and histological changes were assessed at selected time points. Result Statistically significant behavioral improvements were demonstrated on Day 7 and 1 month between saline treated HIE rats and UCB/MNC treated rats. However, at 3 months, the therapeutic improvements were only showed between saline treated HIE animals and MNC treated HIE rats. For histological analysis 1 month after cell injection, the number of functional neurons were statistically increased between saline treated HIE and UCB/MNC/RCF treated HIE rats. At 3 months, the significant increase in functional neurons was only present in MNC treated HIE rats. Conclusion We have used a bilateral temporary occlusion of 60 min, a moderately brain damaged model, for cell therapeutic studies. HUCB mononuclear cell (MNC) therapy showed benefits in neonatal HIE rats in both short and long term behavioral and histological assessments.
Estimation of Cerebral Hemodynamics and Oxygenation During Various Intensities of Rowing Exercise: An NIRS Study

Purpose This study aimed to investigate changes in cerebral hemodynamics and oxygenation at moderate, heavy, maximal and supramaximal intensities of rowing exercise. It also examined whether these changes reflect alterations in sensation of effort and mood. We also aimed to examine the effects of peak pulmonary oxygen consumption (V.O2peak) on cerebral oxygenation. Methods Eleven rowers, consisting out of six athletes and five recreational rowers [two female; age, 27 ± 9 years; height, 171 ± 7 cm, body mass, 67 ± 9 kg; V.O2peak, 53.5 ± 6.5 mL min–1 kg–1] rowed a 13-min session separated by 10 and 3 min, at 70 (Ex70%) and 80% of V.O2peak (Ex80%), respectively, on a rowing ergometer, followed by three sessions of 1-min supramaximal exercise (ExSp). After a warm-up at 60% of V.O2peak (ExM), seven male rowers performed a 2,000 m all-out test (Ex2000). Cardiovascular and respiratory variables were measured. Cerebral oxygenation was investigated by near-infrared time-resolved spectroscopy (TRS) to measure cerebral hemoglobin oxygen saturation (ScO2) and total hemoglobin concentration ([HbT]) in the prefrontal cortex (PFC) quantitatively. We estimated the relative changes from rest in cerebral metabolic rate for oxygen (rCMRO2) using TRS at all intensities. During Ex70% and Ex80%, ratings of perceived exertion (RPE) were monitored, and alteration of the subject’s mood was evaluated using a questionnaire of Positive-and-Negative-Affect-Schedule after Ex70% and Ex80%. Results When exercise intensity changed from Ex70% to Ex80%, the sense of effort increased while ScO2 decreased. [HbT] remained unchanged. After Ex70% and Ex80%, a negative mood state was less prominent compared to rest and was accompanied by increases in both ScO2 and [HbT]. At termination of Ex2000, ScO2 decreased by 23% compared to rest. Changes in ScO2 correlated with V.O2peak only during Ex2000 (r = −0.86; p = 0.01). rCMRO2 did not decrease at any intensities. Conclusion Our results suggest that alterations in the sense of effort are associated with oxygenation in the PFC, while positive changes in mood status are associated with cerebral perfusion and oxygen metabolism estimated by TRS. At exhaustion, the cerebral metabolic rate for oxygen is maintained despite a decrease in ScO2.
Triglyceride Glucose Index Is More Closely Related to Hyperuricemia Than Obesity Indices in the Medical Checkup Population in Xinjiang, China

Background Hyperuricemia (HUA) is a metabolic anomaly with an increased incidence rate, causing a global medical burden. Several studies have confirmed that obesity and insulin resistance (IR) are the risk factors for HUA. Reports on the predictive power of different obesity indices for HUA are limited. This study aimed to compare the association between different general, abdominal, and visceral obesity indices and markers of the IR-triglyceride glucose (TyG) index with serum uric acid (SUA) and to assess the ability of these indices to predict HUA. Methods A total of 2243 participants were recruited from Barkol County Hospital and surrounding township hospitals in Xinjiang. Obesity indices, including the atherogenic index of plasma, cardiometabolic index, visceral adiposity index, lipid accumulation product index, a body shape index, body roundness index, waist circumference, waist-to-height ratio, body mass index, and TyG index, were divided into four quartiles. Moreover, partial correlations and logistic regression were used to analyze the association between these indices and SUA. The area under the curve (AUC) and receiver operating characteristic curves were used to analyze the predictive value of these indices for HUA. Results After controlling for confounding variables, the association between the TyG index and HUA was stronger than that between the obesity indices in both males and females. The odds ratios (ORs) for HUA in the highest quartile of the TyG index were 2.098 (95% confidence interval, 1.555–2.831) in males and 7.788 (95% CI, 3.581–16.937) in females. For males, the AIP, CMI, VAI, LAP index, and TyG index were able to discriminate HUA, and the TyG index showed the highest AUC value of 0.586 (95% CI, 0.557–0.614; P < 0.001). For females, all indices, except BMI, can discriminate HUA. Moreover, the visceral obesity index CMI showed the highest AUC value of 0.737 (95% CI, 0.691–0.782; P < 0.001). Meanwhile, the TyG index had a relatively high AUC value of 0.728 (95% CI, 0.682–0.773; P < 0.001). Conclusion The TyG index was significantly related to HUA and was superior to obesity indices in identifying HUA in the medical checkup population in Xinjiang, China.
Reinforcement Learning With Vision-Proprioception Model for Robot Planar Pushing

We propose a vision-proprioception model for planar object pushing, efficiently integrating all necessary information from the environment. A Variational Autoencoder (VAE) is used to extract compact representations from the task-relevant part of the image. With the real-time robot state obtained easily from the hardware system, we fuse the latent representations from the VAE and the robot end-effector position together as the state of a Markov Decision Process. We use Soft Actor-Critic to train the robot to push different objects from random initial poses to target positions in simulation. Hindsight Experience replay is applied during the training process to improve the sample efficiency. Experiments demonstrate that our algorithm achieves a pushing performance superior to a state-based baseline model that cannot be generalized to a different object and outperforms state-of-the-art policies which operate on raw image observations. At last, we verify that our trained model has a good generalization ability to unseen objects in the real world.
Therapeutic Effects of Berberine on Liver Fibrosis are associated With Lipid Metabolism and Intestinal Flora

Liver cirrhosis is a form of liver fibrosis resulting from chronic hepatitis caused by various liver diseases, such as viral hepatitis, alcoholic liver damage, nonalcoholic steatohepatitis, autoimmune liver disease, and by parasitic diseases such as schistosomiasis. Liver fibrosis is the common pathological base and precursors of cirrhosis. Inflammation and disorders of lipid metabolism are key drivers in liver fibrosis. Studies have determined that parts of the arachidonic acid pathway, such as its metabolic enzymes and biologically active products, are hallmarks of inflammation, and that aberrant peroxisome proliferator-activated receptor gamma (PPARγ)-mediated regulation causes disorders of lipid metabolism. However, despite the ongoing research focus on delineating the mechanisms of liver fibrosis that underpin various chronic liver diseases, effective clinical treatments have yet to be developed. Berberine (BBR) is an isoquinoline alkaloid with multiple biological activities, such as anti-inflammatory, anti-bacterial, anti-cancer, and anti-hyperlipidemic activities. Many studies have also found that BBR acts via multiple pathways to alleviate liver fibrosis. Furthermore, the absorption of BBR is increased by nitroreductase-containing intestinal flora, and is strengthened via crosstalk with bile acid metabolism. This improves the oral bioavailability of BBR, thereby enhancing its clinical utility. The production of butyrate by intestinal anaerobic bacteria is dramatically increased by BBR, thereby amplifying butyrate-mediated alleviation of liver fibrosis. In this review, we discuss the effects of BBR on liver fibrosis and lipid metabolism, particularly the metabolism of arachidonic acid, and highlight the potential mechanisms by which BBR relieves liver fibrosis through lipid metabolism related and intestinal flora related pathways. We hope that this review will provide insights on the BBR-based treatment of liver cirrhosis and related research in this area, and we encourage further studies that increase the ability of BBR to enhance liver health.
Long-Term Biocompatibility of a Highly Viscously Thiol-Modified Cross-Linked Hyaluronate as a Novel Vitreous Body Substitute

Purpose: In surgical ophthalmology, the treatment of complicated retinal and vitreous diseases is one of the central challenges. For this purpose, the vitreous body is removed as part of the standard therapy and replaced by a temporary tamponade to stabilize the position of the retina. Since the tamponading properties of previous materials such as silicone oils, gases, or semi-fluorinated alkanes are a combination of their surface tension and their buoyancy vector, they cannot completely fill the vitreous cavity. The aim of this work was to test in vivo a novel vitreous body substitute (ViBos strong) based on cross-linked hyaluronic acid for its compatibility. Methods: A pars plana vitrectomy with posterior vitreous detachment was performed in the right eye of 18 pigmented rabbits, with subsequent injection of ViBos strong. Follow-up examination included slit-lamp examination, funduscopy, intraocular pressure measurements (IOP), optical coherence tomography (OCT), and electroretinogram (ERG) measurements. The rabbits were sacrificed at three different time points (1, 3, and 6 months; each 6 animals) and examined macroscopically and prepared for histological examination (HE staining) and immunohistochemistry (Brn3a and glial fibrillary acidic protein (GFAP)). Results: ViBos strong demonstrated good intraoperative handling and remained stable for at least 1 month and degraded slowly over 6 months. IOP was within clinical acceptable values at all follow-up examinations. Retinal function was well preserved after instillation of the hydrogel and comparable to the untreated eye after 6 months in OCT, ERG, and histological examinations. An increase in the GFAP expression was found in the surgery eyes, with a peak in the 3-month group. The Brn3a expression was not significantly affected by vitrectomy with ViBos strong. Conclusion: Highly viscously thiol-modified cross-linked hyaluronate showed a good biocompatibility in rabbit eyes over 6 months after vitrectomy, making it a promising potential as a vitreous substitute.
Repetitive Restricted Behaviors in Autism Spectrum Disorder: From Mechanism to Development of Therapeutics

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social communication, social interaction, and repetitive restricted behaviors (RRBs). It is usually detected in early childhood. RRBs are behavioral patterns characterized by repetition, inflexibility, invariance, inappropriateness, and frequent lack of obvious function or specific purpose. To date, the classification of RRBs is contentious. Understanding the potential mechanisms of RRBs in children with ASD, such as neural connectivity disorders and abnormal immune functions, will contribute to finding new therapeutic targets. Although behavioral intervention remains the most effective and safe strategy for RRBs treatment, some promising drugs and new treatment options (e.g., supplementary and cell therapy) have shown positive effects on RRBs in recent studies. In this review, we summarize the latest advances of RRBs from mechanistic to therapeutic approaches and propose potential future directions in research on RRBs.
Mechanisms of Senescence-Related NKG2D Ligands Release and Immune Escape Induced by Chemotherapy in Neuroblastoma Cells

Chemotherapy-induced senescence promotes immunocyte aggregation in the tumor microenvironment by upregulating the surface expression of activating ligands in cancer cells. However, these senescent tumor cells cannot be completely cleared and can induce tumor recurrence. Previous studiesshowed that soluble natural killer (NK) group 2D (NKG2D) ligands impair the recognition of multiple immune cells. In this study, we established an in vitro senescence model using neuroblastoma cells subjected to low-dose Chemotherapeutic drug doxorubicin or the Aurora A inhibitor MLN8237. The results showed that different neuroblastoma cell lines showed increased secretion of the NKG2D ligand MHC class I polypeptide-related sequence A/B (MICA/B) following proteolysis after treatment, with MICA/B subsequently recruited to exosomes to downregulate NKG2D expression in NK cells. Interestingly, disintegrin and metalloproteinase domain-containing 10 (ADAM10) was upregulated in senescent tumor cells, and combined treatment with the ADAM10 inhibitor GI254023X and chemotherapeutic drugs inhibited MICA/B secretion and enhanced recognition and killing by NK cells. Additionally, we found that expression of the long noncoding RNA MALAT1 was significantly increased in senescent neuroblastoma cells, and that MALAT1 served as a sponge for microRNA (miR)-92a-3p to counteract miR-92a-3p-mediated repression of ADAM10 levels. Furthermore, administration of a MALAT1 inhibitor or an miR-92a-3p mimic reduced the MICA/B shedding and enhanced recognition and killing by NK cells. These results confirmed that low-dose chemotherapy induces senescence in neuroblastoma cells, and that senescent tumor cells promote the shedding of the NKG2D ligand MICA/B through the MALAT1/miR-92a/ADAM10 axis, thereby contributing to the formation of a suppressive immune microenvironment and promoting immune escape.