Miracle-dz/UniFAR-FTUs huggingface dataset:
Exposure to Maternal Immune Activation Causes Congenital Unfolded Protein Response Defects and Increases the Susceptibility to Postnatal Inflammatory Stimulation in Offspring

Background A number of childhood diseases have been identified, such as severe infection or autoinflammatory disease, in which immune overreaction against inflammation is a possible underlying mechanism. Previous reports have demonstrated that fetal cells exposed to maternal immune activation (MIA) induced by polyriboinosinic-polyribocytidylic acid [poly(I:C)] exhibited hypersensitivity to inflammation in vitro. However, the details of this mechanism remain unclear. Therefore, this study aimed to reveal the reaction to inflammation in offspring exposed to MIA in the prenatal period, as well as its molecular mechanism, using a viral infection mouse model. Materials and Methods Pregnant mice at 12.5, 14.5, and 16.5 days post coitum were injected intraperitoneally with poly(I:C) 20 mg/kg body weight (BW) or saline. Offspring aged 3–4 weeks received the second injection of 20 mg/kg BW or 4 mg/kg BW poly(I:C) or saline. Serum and tissues were collected at 2, 24, 48, and 72 h after the postnatal injection. The cytokine profile, histopathology of organs, and unfolded protein response (UPR) in offspring were examined. Results The serum levels of interleukin (IL)-6, IL-17, and interferon-γ were significantly higher in the MIA group, and acute liver necrosis was detected. Moreover, failure in UPR was observed in the MIA group compared with that in the control group. Conclusion Overall, MIA exposure in utero caused failure in UPR as well as immune overreaction to the second attack of inflammation in offspring. Our results suggested that prenatal exposure to MIA might contribute to the congenital inflammatory constitution after birth.
Effects of Transcutaneous Electrical Acupoint Stimulation (TEAS) on Postoperative Recovery in Patients with Gastric Cancer: A Randomized Controlled Trial

Purpose Transcutaneous electrical acupoint stimulation (TEAS) is an innovative choice for postoperative pain management. However, the safety and effectiveness of this traditional Chinese medicine (TCM) therapy for patients who underwent gastrectomy is largely unknown. So, the purpose of this study is to evaluate the safety and effectiveness of TEAS for patients who underwent gastrectomy. Patients and Methods We recruited 96 patients with gastric cancer from May 2019 to November 2019; 82 patients were enrolled, and 81 patients completed. Patients were randomly assigned to TEAS group (TG) received TEAS on postoperative day (POD) 1–3 or control group (CG) at a 1:1 ratio. The primary outcomes were pain score and consumption of analgesics. The secondary were the time of first postoperative flatus and defecation, frequency of postoperative nausea, vomiting, distention, diarrhea, comfort of semi-fluid diet, Clavien-Dindo grade (C-D grade) and length of postoperative day. We performed hematological analysis to explore the possible mechanisms. Results Overall, 81 patients were enrolled included in the analysis. Compared with CG, pain scores in TG were lower on POD 1–5 (average: 2.55±0.21 vs 3.10±0.42, P<0.001), and the use rate of opioids was lower (43.9 vs 75.0, P=0.004); time of first postoperative flatus (55.63±16.74 vs 72.60±20.92, P<0.001) and defecation (72.20±16.24 vs 95.78±17.75, P<0.001) were shorter; the frequency of nausea were fewer (1.88±1.09 vs 2.58±0.77, P=0.029) and patients were more comfortable with semi-fluid diet (7.63±0.63 vs 6.93±0.69, P<0.001); among the hematologic results, β-endorphin (β-End), interleukin-2 (IL-2), motilin (MTL) on POD 3, POD 5 were lower, 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were higher. And no adverse event was reported. Conclusion TEAS can relieve postoperative pain and promote the recovery of gastrointestinal function. Consequently, it can be an adjunctive therapy to enhance postoperative recovery for patients after gastrectomy.
L-Cysteine Provides Neuroprotection of Hypoxia-Ischemia Injury in Neonatal Mice via a PI3K/Akt-Dependent Mechanism

Background Previous work within our laboratory has revealed that hydrogen sulfide (H2S) can serve as neuroprotectant against brain damage caused by hypoxia-ischemia (HI) exposure in neonatal mice. After HI insult, activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has been shown to be implicated in neuro-restoration processes. The goal of the current study was to determine whether the neuroprotective effects of H2S were mediated by the PI3K/Akt signaling pathway. Methods The mouse HI model was built at postnatal day 7 (P7), and the effects of L-Cysteine treatment on acute brain damage (72 h post-HI) and long-term neurological responses (28 days post-HI) were evaluated. Nissl staining and Transmission electron microscopy were used to evaluate the neuronal loss and apoptosis. Immunofluorescence imaging and dihydroethidium staining were utilized to determine glial cell activation and ROS content, respectively. Results Quantitative results revealed that L-Cysteine treatment significantly prevented the acute effects of HI on apoptosis, glial cell activation and oxidative injury as well as the long-term effects upon memory impairment in neonatal mice. This protective effect of L-Cysteine was found to be associated with the phosphorylation of Akt and phosphatase and a tensin homolog deletion on chromosome 10 (PTEN). Following treatment with the PI3K inhibitor, LY294002, the neuroprotective effects of L-Cysteine were attenuated. Conclusion PTEN/PI3K/Akt signaling was involved in mediating the neuroprotective effects of exogenous H2S against HI exposure in neonatal mice.
Inhibitory effect and mechanism of action (MOA) of hirsutine on the proliferation of T-cell leukemia Jurkat clone E6-1 cells

Background The bark of Uncaria rhynchophylla has been traditionally used to treat convulsion, bleeding, hypertension, auto-immune conditions, cancer, and other diseases. The main focus of this research is done for the purpose of exploring the antitumor activity and mechanism of action (MOA) for hirsutine isolated from U. rhynchophylla. Methods Jurkat clone E6-1 cells were treated using 10, 25 and 50 μM for 48 h. Inhibition of cell proliferation due to hirsutine treatment was evaluated by CCK8 assay. Flow cytometry was applied to ascertain Jurkat cell cycle progression and apoptosis after treatment with 10, 25 and 50 μM hirsutine for 48 h. The expression and level of the apoptosis-related genes and proteins was analyzed by Real-time Quantitative polymerase chain reaction (qPCR) and Western blotting method, respectively. Results CCK8 analyses revealed that hirsutine could significantly inhibit the proliferation of Jurkat clone E6-1 cells, in a concentration and time-dependent fashion. Flow cytometry assays revealed that hirsutine could drive apoptotic death and G0/G1 phase arrest in Jurkat cells. Apoptotic cells frequencies were 4.99 ± 0.51%, 13.69 ± 2.00% and 40.21 ± 15.19%, and respective cell cycle arrest in G0/G1 accounted for 34.85 ± 1.81%, 42.83 ± 0.70% and 49.12 ± 4.07%. Simultaneously, compared with the control group, Western blot assays indicated that the up-regulation of pro-apoptotic Bax, cleaved-caspase3, cleaved-caspase9 and Cyto c proteins, as well as the down-regulation of Bcl-2 protein which guards against cell death, might be correlated with cell death induction and inhibition of cell proliferation. QPCR analyses indicated that hirsutine could diminish BCL2 expression and, at the same time, improve Bax, caspase-3 and caspase-9 mRNA levels, thus reiterating a putative correlation of hirsutine treatment in vitro with apoptosis induction and inhibition of cell proliferation (p-value < 0.05). Excessive hirsutine damages the ultrastructure in mitochondria, leading to the release of Cyt c from the mitochondria to cytoplasm in Jurkat clone E6-1 cells, thereby inducing the activated caspase cascade apoptosis process through a mitochondria-mediated pathway. Conclusion An important bioactive constituent—hirsutine—appears to have antitumor effects in human T-cell leukemia, thus enlightening the use of phytomedicines as a novel source for tumor therapy. It is speculated that hirsutine may induce apoptosis of Jurkat Clone E6-1 cells through the mitochondrial apoptotic pathway.
Clozapine Efficacy in a Case of Severe Treatment-Resistant Postpartum Psychosis

Background The postpartum period is a difficult time for mother and family. Unfortunately, in some cases, two psychiatric complications may occur: postpartum psychoses (PPP) with a prevalence of 0.2% and a very low incidence of 0.25–0.50 per 1000 deliveries, and post-natal depressions with an incidence of 10 to 20% per 1000 deliveries. The onset of postpartum psychosis is in the first 4 weeks after childbirth with symptoms such as emotional lability, cognitive disorganization, delusional beliefs and hallucinations. It requires hospitalization due to the high risk of suicide and infanticide. The studies reveal that the treatment can include FGAs (first-generation antipsychotics), such as haloperidol, and SGAs (second-generation antipsychotics), such as olanzapine, quetiapine and risperidone. The literature is scarce in what resistant PPP is concerned and no such cases treated with clozapine have been reported, according to our knowledge. The present case report focuses on a female diagnosed with PPP who was treated with clozapine due to the lack of response to adequate dosage of 2 second-generation antipsychotics. Case Presentation We present the case of a 30-year-old primiparous woman on her 3rd day after delivery, admitted in the psychiatric emergency unit for agitation, intrusive thoughts with a content frequently related to the infant, ideas of reference, disorganized speech, bizarre behavior, verbal stereotypes, insomnia and anxiety. Due to lack of response to adequate dosage of 2 second-generation antipsychotics, clozapine was initiated up to 250 mg/day. The symptoms remitted in the next 5 days and the patient was discharged. After discharge, at the patient’s request, clozapine was replaced by olanzapine. Visit at 1 year revealed full remission of symptoms. Conclusion Although data is extremely limited, clozapine has been shown to be effective and safe in a severe case of treatment-resistant PPP.
Diagnostic significance of circulating miRNAs in Kawasaki disease in China

Abstract Background: There is no golden standard for the diagnosis of Kawasaki disease (KD), the most common cause of acquired heart disease in children in many countries. In recent years, many studies have focused on the relationship between microRNAs (miRNAs) and KD. Thus, we perform this meta-analysis to understand the role of circulating miRNAs as a biomarker to detect KD. Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through March 10, 2019. Meta-disc 1.4 and STATA 15.1 (Stata Corporation, College Station, TX) were used to conduct the meta-analysis. Results: Six eligible articles were included in this meta-analysis. The overall performance of total mixed miRNAs detection was: pooled sensitivity, 0.7 (95% confidence interval, 0.66–0.74); pooled specificity, 0.87 (95% confidence interval, 0.83–0.90); and area under the summary receiver operating characteristic curves value (SROC), 0.8302. The meta-regression analysis indicated that the specimen types, the composition of the control group, and types of the reference miRNA were not responsible for the existing heterogeneities. The subgroup analysis showed that SROC of the plasma group (0.8890) was more significant than the serum group (0.7204), and SROC of the non-healthy control group (0.9622) was more significant than the healthy control group (0.8096). Conclusions : This is the first meta-analysis show that miRNAs may be used as novel biomarkers for detecting KD, especially for distinguishing KD from other febrile diseases. More studies are needed in the future to clarify the association between KD and miRNAs. PROSPERO registration number: CRD42019129976
Interspecies Competitive Effects in Reduction of Organohalides in Connelly Iron Columns

Interspecies competitive effects on the degradation of two alkyl halides (1-bromo-2-chloroethane, BCA, and 1,1,2-trichloroethane, 1,1,2-TCA) and three vinyl halides (trichloroethylene, TCE; cis-dichloroethylene, cis-DCE; and trans-dichloroethylene, trans-DCE) were investigated in column experiments using Connelly iron. The presence of vinyl halides as cosolutes diminished the removal efficiencies of all compounds investigated except TCE. The presence of BCA led to a decrease in iron reactivity toward cis- DCE as a result of interspecies competition with the accumulating degradation product ethylene. Although ethylene had an inhibitory effect on some organohalides, it reacted slowly itself, consistent with the notion that its effect stems primarily from competitive sorption to reactive sites rather than from slow regeneration of reactive sites at the particle–water interface. Competitive effects observed in dual-solute experiments could be modeled via Langmuir-Hinshelwood-Hougen-Watson (LHHW) kinetics. The.
Crohn's Disease Activity Evaluation by Transabdominal Ultrasonography: Correlation with Double‐Balloon Endoscopy

Transabdominal ultrasonography (US) has been reported as a useful tool for evaluating Crohn's disease (CD) activity. Endoscopic findings and Crohn's disease activity index (CDAI) are currently considered the gold standard for assessing CD activity. We assessed the correlation between US and double‐balloon endoscopy (DBE), and CDAI for evaluating CD activity.
A Mechanistic In Vivo/Ex Vivo Pharmacokinetic‐Pharmacodynamic Model of Tenofovir for HIV Prevention

Defining tissue and plasma‐specific prophylactic drug concentrations is central to pre‐exposure prophylaxis product development for sexual transmission of HIV‐1. Pharmacokinetic (PK) data from study RMP‐02/MTN‐006 comparing single dose oral tenofovir disoproxil fumarate with single and multiple dose rectal tenofovir (TFV) gel administration in HIV‐1 seronegative adults was used to construct a multicompartment plasma‐rectal tissue population PK model for TFV and tenofovir‐diphosphate (TFVdp) in plasma and rectal tissue. PK data were collected in five matrices: TFV (plasma, rectal tissue homogenate), TFVdp (peripheral blood mononuclear cells, rectal mononuclear cells (MMCs), rectal tissue homogenate). A viral growth compartment and a delayed effect compartment for p24 antigen expression measured from an ex vivo explant assay described HIV‐1 infection and replication. Using a linear PK/pharmacodynamic model, MMC TFVdp levels over 9,000 fmol/million cells in the explant assay provided apparent viral replication suppression down to 1%. Parameters were estimated using NONMEM version 7.4.
A high-throughput phenotyping algorithm is portable from adult to pediatric populations

OBJECTIVE Multimodal automated phenotyping (MAP) is a scalable, high-throughput phenotyping method, developed using electronic health record (EHR) data from an adult population. We tested transportability of MAP to a pediatric population. MATERIALS AND METHODS Without additional feature engineering or supervised training, we applied MAP to a pediatric population enrolled in a biobank and evaluated performance against physician-reviewed medical records. We also compared performance of MAP at the pediatric institution and the original adult institution where MAP was developed, including for 6 phenotypes validated at both institutions against physician-reviewed medical records. RESULTS MAP performed equally well in the pediatric setting (average AUC 0.98) as it did at the general adult hospital system (average AUC 0.96). MAP's performance in the pediatric sample was similar across the 6 specific phenotypes also validated against gold-standard labels in the adult biobank. CONCLUSIONS MAP is highly transportable across diverse populations and has potential for wide-scale use.
LcERF2 Modulates Cell Wall Metabolism by Directly Targeting a UDP-glucose 4-epimerase Gene to Regulate Pedicel Development and Fruit Abscission of Litchi.

Elucidating the biochemical and molecular basis of premature abscission in fruit crops should help develop strategies to enhance fruit set and yield. Here, we report that LcERF2 contributes to differential abscission rates and responses to ethylene in Litchi chinensis. Reduced LcERF2 expression in litchi was observed to reduce fruit abscission, concurrent with enhanced pedicel growth with increased levels of hexoses, particularly galactose, as well as the pectin abundance in cell wall. Ecoptic expression of LcERF2 in Arabidopsis thaliana caused enhanced petal abscission, together with retarded plant growth and reduced pedicel galactose and pectin contents. Transcriptome analysis indicated that LcERF2 modulates the expression of genes involved in cell wall modification. Yeast one-hybrid, dual-luciferase reporter, and electrophoretic mobility shift assays all demonstrated that a UDP-glucose 4-epimerase gene (LcUGE) was the direct downstream target of LcERF2. This result was further supported by a significant reduction in expression of the A. thaliana homolog, AtUGE2-4, in response to LcERF2 over-expression. Significantly reduced pedicel diameter and enhanced litchi fruit abscission were observed in response to the LcUGE silencing. We conclude that LcERF2 mediates fruit abscission by orchestrating cell wall metabolism and thus pedicel growth, in part by repressing the expression of LcUGE.
Extracellular vesicle-derived miR-26b-5p is up-regulated in the serum of patients with diabetic retinopathy.

BACKGROUND Diabetic retinopathy (DR) is a severe complication of diabetes; however, the pathogenesis of DR has not been completely clarified, which is mostly dependent on the molecular pathology. To investigate key serum-derived miRNAs associated with DR. METHODS miRNA expression profile arrays of human umbilical vein endothelial cells (HUVECs) treated with glucose were downloaded from the Gene Expression Omnibus (GEO) database (GSE74296). Weighted gene co-expression network analysis (WGCNA) was performed to obtain hub miRNAs, which were verified in HUVECs treated with 40 mM and 5 mM glucose, respectively. Meanwhile, serum samples of patients with DR and healthy controls were collected, and EVs were extracted from the patients' serum by ultracentrifugation. Hub miRNAs associated with endothelial dysfunction were verified in healthy individuals before and after treatment of patients with DR, by qRT-PCR. RESULTS These miRNAs were categorized into six modules, among which miR-26b-5p had a strong association with other modules. This miRNA was also one of the hyperglycemia-induced miRNAs related to endothelial dysfunction. miR-26b-5p was upregulated in HUVECs treated with 40 mM glucose and in the serum of patients with DR before and after treatment Furthermore, miR-26b-5p was slightly up-regulated in serum-derived EVs but not in serum without EVs in DM patients. CONCLUSION Our results suggest that EVs derived from miR-26b-5p are up-regulated in the serum of patients with DR.
Escherichia coli Nissle 1917 administered as a dextranomar microsphere biofilm enhances immune responses against human rotavirus in a neonatal malnourished pig model colonized with human infant fecal microbiota

Human rotavirus (HRV) is a leading cause of diarrhea in children. It causes significant morbidity and mortality, especially in low- and middle-income countries (LMICs), where HRV vaccine efficacy is low. The probiotic Escherichia coli Nissle (EcN) 1917 has been widely used in the treatment of enteric diseases in humans. However, repeated doses of EcN are required to achieve maximum beneficial effects. Administration of EcN on a microsphere biofilm could increase probiotic stability and persistence, thus maximizing health benefits without repeated administrations. Our aim was to investigate immune enhancement by the probiotic EcN adhered to a dextranomar microsphere biofilm (EcN biofilm) in a neonatal, malnourished piglet model transplanted with human infant fecal microbiota (HIFM) and infected with rotavirus. To create malnourishment, pigs were fed a reduced amount of bovine milk. Decreased HRV fecal shedding and protection from diarrhea were evident in the EcN biofilm treated piglets compared with EcN suspension and control groups. Moreover, EcN biofilm treatment enhanced natural killer cell activity in blood mononuclear cells (MNCs). Increased frequencies of activated plasmacytoid dendritic cells (pDC) in systemic and intestinal tissues and activated conventional dendritic cells (cDC) in blood and duodenum were also observed in EcN biofilm as compared with EcN suspension treated pigs. Furthermore, EcN biofilm treated pigs had increased frequencies of systemic activated and resting/memory antibody forming B cells and IgA+ B cells in the systemic tissues. Similarly, the mean numbers of systemic and intestinal HRV-specific IgA antibody secreting cells (ASCs), as well as HRV-specific IgA antibody titers in serum and small intestinal contents, were increased in the EcN biofilm treated group. In summary EcN biofilm enhanced innate and B cell immune responses after HRV infection and ameliorated diarrhea following HRV challenge in a malnourished, HIFM pig model.
Future fertility of patients with zero oocytes yield in their first IVF cycle attempt

Purpose We aim to estimate the future fertility of patient undergoing their first IVF cycle attempt with no oocyte retrieved, and to identify factors that might predict those who will conceive in subsequent IVF cycle attempt. Methods A cohort retrospective study of all consecutive women attending our IVF unit, for their first IVF cycle attempt, between January 2013 to December 2019, who reached the ovum pick-up (OPU) stage with zero oocyte retrieved. Patients’ characteristics and infertility-treatment-related variables in the first IVF cycle attempt were compared between those who conceived in a subsequent cycle and those who did not. Moreover, infertility-treatment-related variables during successful cycles resulting in pregnancy were compared to those without. Results 59 met the study inclusion criteria, yielding zero oocytes. During the follow-up period, 12 (20.3%) women conceived (one conceived twice), and 8 (14%) gave birth to a live infant. Cumulative live-birth rate per OPU and per patients were 4% and 14%, respectively. Clinical pregnancies were achieved after 3.61+1.4 cycle attempts (range: 1–6), with no live-births following the fifth IVF cycle attempt. No in-between group differences were observed in ovarian stimulation variables of their first IVF cycle attempt. Moreover, in those cycles resulting in pregnancy, patients achieved a significantly higher number of fertilized oocytes (2.15+1.5 vs 0.94+1.5, respectively; p<0.01) and a higher mean top-quality embryos (TQE) (1.76+0.9 vs 0.73+1.2, respectively; p<0.003). Conclusion Women yielding zero oocytes at their first IVF cycle attempt, may achieve 14% cumulative live-birth rate after 5 IVF cycle attempts. Moreover, those who conceived in subsequent IVF cycle attempts were those achieving 2 or more fertilized oocytes/TQE.